МАТЕРИАЛЫ ДЛЯ КУЛЬТИВИРОВАНИЯ КЛЕТОК

МУЛЬТИПОТЕНТНЫЕ СТВОЛОВЫЕ КЛЕТКИ ВНЕПЕЧЕНОЧНЫХ ЖЕЛЧНЫХ ПУТЕЙ И СПОСОБЫ ИХ ВЫДЕЛЕНИЯ

... 1. Композиция, содержащая мультипотентные стволовые клетки/клетки-предшественники млекопитающего, способные дифференцироваться в несколько эндодермальных клеточных линий, причем клетки получают из ткани желчных путей млекопитающего.2. Композиция по п.1, в которой мультипотентная стволовая клетка/клетка-предшественник представляет собой мультипотентную стволовую клетку.3. Композиция по п.1, в которой эндоермальная клеточная линия представляет собой линию печеночных клеток, линию билиарных клеток, линию панкреатических клеток или их комбинацию.4. Композиция по п.1, в которой ткань желчных путей представляет собой любую область желчных путей, включая ворота, общий печеночный проток, пузырный проток, общий проток, общий гепатопанкреатический проток и желчный пузырь.5. Композиция по п.1, в которой млекопитающим является человек.6. Композиция по п.5, в которой млекопитающее-человек представляет собой плод, новорожденного, ребенка, взрослого или умершего человека вплоть до момента 72 часа после ...

Fibrosis model on a chip

Systems and methods for immobilizing extracelluar matrix material on organ on chip, multilayer microfluids microdevices, and three-dimensional cell culture

Lung disease models on a chip

Fibrosis model on a chip

The presently disclosed subject matter provides a biomimetic organ model, and methods of its production and use. In one exemplary embodiment, the biomimetic organ model can be a multi-layer model including a at least two microchannels and at least one chamber slab with at least one membrane coated with cells disposed between at least one microchannel and the at least one chamber slab. In another exemplary embodiment, the biomimetic organ disease model can be a five- layer model including a first and second microchannel with a membrane-gel layer- membrane coated or encompassing cells disposed between the microchannels. In certain embodiments, at least one device can be coupled to the biomimetic organ model that delivers an agent to at least one microchannel.

Compositions and methods of cell attachment

Compositions and methods of cell attachment

Compositions, devices and methods are described for improving adhesion, attachment, and/or differentiation of cells in a microfluidic device or chip. In one embodiment, one or more ECM proteins are covalently coupled to the surface of a microchannel of a microfluidic device. The microfluidic devices can be stored or used immediately for culture and/or support of living cells such as mammalian cells, and/or for simulating a function of a tissue, e.g., a liver tissue, muscle tissue, etc. Extended adhesion and viability with sustained function over time is observed.

Adipose tissue matrices

The present disclosure provides tissue products produced from adipose tissues, as well as methods for producing such tissue products. The tissue products can include acellular extracellular matrices. In addition, the present disclosure provides systems and methods for using such products.

Cell culturing materials

A material for binding to a cell culturing protein is disclosed. The material contains a bulk-modified elastomer comprising a plurality of fatty acid moieties covalently bound to the elastomer bulk, wherein the carboxylic acid groups of said moieties are available to provide said binding. Also disclosed are a fluidic device module, a cell culturing scaffold, a fluidic device, the method of synthesizing such a material and a drug testing method. With such a material, a (monolithic) fluidic device module may be manufactured in as few as a single step injection molding process.

Engineered tissue substitute system

Compositions and methods of preparation and use are provided for an engineered tissue substitute system comprising collagen, glycosaminoglycan and hydrogel in a cross-linked matrix. The compositions may be further lyophilized and reconstituted with a physiological fluid prior to use in methods, such as in the treatment of wounds, tissue engineering and cell transplantation.

Lung disease models on a chip

The presently disclosed subject matter provides a biomimetic lung disease model, and methods of its production and use. In one exemplary embodiment, the biomimetic lung disease model can include a first and second microchannel with a membrane coated with airway epithelial cells disposed between the microchannels and at least one device coupled to the biomimetic model that delivers an agent to at least one microchannel. In certain embodiments, the agent is cigarette smoke.

MULTIPOTENT STEM CELLS FROM THE EXTRAHEPATIC BILIARY TREE AND METHODS OF ISOLATING SAME

The present invention relates to a multipotent stem cell, multipotent cell populations, and an enriched multipotent cell population, each found in fetal, neonatal, pediatric, and adult biliary tree tissue and up to 72 hours post mortem (although preferentially, within 10 hours post mortem) and capable of maturing into multiple endodermal tissues that include liver, biliary and pancreatic tissues. The multipotent stem/progenitor cell and cell populations are found in peribiliary glands, and progenitors descending from them are present throughout the biliary tree including in the gallbladder. High numbers of the peribiliary glands are found in the branching locations of the biliary tree such as hilum, common hepatic duct, cystic duct, common duct, common hepato-pancreatic duct and gallbladder. Related multipotent cells, multipotent cell populations and their descendent progenitors are found throughout the biliary tree including in the gall bladder, which does not have peribiliary glands.

HYDROGEL-BASED VASCULAR LINEAGE CELL GROWTH MEDIA AND USES THEREOF

A medium for growing vascular lineage cells is described. The vascular lineage cell growth medium includes an oligosaccharide-based hydrogel and a growth factor that promotes vascularization by vascular lineage cells.

THREE DIMENSIONAL HYDROGELS FOR CULTURING ORGANOIDS

The invention provides hydrogels and methods for three-dimensional (3D) culture of adult epithelial stem cells and uses thereof.

CELL CULTURING MATERIALS

A material for binding to a cell culturing protein is disclosed. The material contains a bulk-modified elastomer comprising a plurality of fatty acid moieties covalently bound to the elastomer bulk, wherein the carboxylic acid groups of said moieties are available to provide said binding. Also disclosed are a fluidic device module, a cell culturing scaffold, a fluidic device, the method of synthesizing such a material and a drug testing method. With such a material, a (monolithic) fluidic device module may be manufactured in as few as a single step injection molding process.

DEVICES AND METHODS FOR SINGLE CELL ANALYSIS

The present disclosure provides systems, methods, and devices for the simultaneous determination of a single cell's response to a stimuli and characterization of its cell response. The present disclosure further provides methods for detection of disease state, clinical management of a subject suffering from a disease, drug screening, prediction of drug response, and stands to help direct drug and diagnostic development for the treatment of disease.

SYNTHETIC SURFACES FOR CULTURING CELLS IN CHEMICALLY DEFINED MEDIA

Synthetic surfaces capable of supporting culture of eukaryotic cells including stem cells and undifferentiated human embryonic stem cells in a chemically defined medium include a swellable (meth)acrylate layer and a polypeptide conjugated to the swellable (meth)acrylate layer. The swellable (meth)acrylate layer may be formed by polymerizing monomers in a composition that includes a carboxyl group-containing (meth)acrylate monomer, a cross-linking (di- or higher-functional) (meth)acrylate monomer, and a hydrophilic monomer capable of polymerizing with the carboxyl group-containing (meth)acrylate monomer and the cross-linking (meth)acrylate monomer. The swellable (meth)acrylate layer has an equilibrium water content in water of between about 5% and about 70%. The conjugated peptide may include an RGD amino acid sequence.

METHOD OF ENGRAFTING CELLS FROM SOLID TISSUES

A method of repairing diseased or dysfunctional organs or of establishing a model system of a disease state is provided. For repairing diseased organs, the method involves engraftment of cells from healthy tissue of the diseased or dysfunctional organ admixed with gel-forming biomaterials and nutrient medium, signaling molecules and extracellular matrix components that can be made insoluble rapidly upon transplantation to form a graft. In this way, the graft mimics the complexity of the native microenvironment with a minimum number of components that allow transplantation of cells to successfully engraft, expand and then rebuild part or the entirety of the diseased or dysfunctional organ. In the case of using grafting methods for establishing a disease model, diseased cells may be transplanted in the biomaterials and into experimental hosts.

POLYMER-BASED MATERIAL, HAVING COVALENTLY BOUND ENZYMATICALLY DEGRADED PEPTIDE SEQUENCES

PHASE SEPARATED COMPOSITE

Encapsulation and cardiac differentiation of hiPSCs in 3D PEG-fibrinogen hydrogels

The present invention relates to the production of cell cultures and tissues from undifferentiated pluripotent stem cells using three-dimensional biomimetic materials. The resultant cell cultures or tissues can be used in any of a number of protocols including testing chemicals, compounds, and drugs. Further, the methods and compositions of the present invention further provide viable cell sources and novel cell delivery platforms that allow for replacement of diseased tissue and engraftment of new cardiomyocytes from a readily available in vitro source. The present invention includes novel methods required for the successful production of cell cultures and tissues, systems and components used for the same, and methods of using the resultant cell and tissue compositions.

POLYMER MATRICES FOR CELL CULTURE

Synthetic cell culture surfaces, including a hydrophobe modified cellulose or an hydroxylated acrylate polymer composition and optionally including a silica source, cell culture coating and cell culture articles incorporating the composition, and methods of making and using the articles for cell culture, as defined herein.

МУЛЬТИПОТЕНТНЫЕ СТВОЛОВЫЕ КЛЕТКИ ВНЕПЕЧЕНОЧНЫХ ЖЕЛЧНЫХ ПУТЕЙ И СПОСОБЫ ИХ ВЫДЕЛЕНИЯ

Изобретение относится к биотехнологии, а именно к способу получения мультипотентных стволовых клеток/клеток-предшественников млекопитающего, а также к применению клеток, полученных данным способом. Получают ткани желчных путей, которые выбирают из группы, состоящей из ворот, общего печеночного протока, пузырного протока, общего протока, общего гепатопанкреатического протока, желчного пузыря или их комбинаций. Получают посредством иммуноселекции и/или в селективных условиях культивирования клетки, позитивные по меньшей мере по одному маркеру, характерному для линии печеночных клеток на ранней стадии, выбранному из HNF6, HES1, CK19, альбумина и альфа-фетопротеина (AFP); по меньшей мере по одному маркеру, характерному для линии панкреатических клеток на ранней стадии, выбранному из PDX1, PROX1, NGN3 и инсулина; по меньшей мере по одному из генов-маркеров плюрипотентности, выбранному из SOX2, NANOG, KLF4, ОСТ4А и ОСТ4. Полученные стволовые клетки не экспрессируют или слабо экспрессируют маркеры ...

МУЛЬТИПОТЕНТНЫЕ СТВОЛОВЫЕ КЛЕТКИ ВНЕПЕЧЁНОЧНЫХ ЖЕЛЧНЫХ ПУТЕЙ И СПОСОБЫ ИХ ВЫДЕЛЕНИЯ

Настоящее изобретение относится к клеточной биологии и медицине и раскрывает композицию для трансплантации популяции клеток пациенту и способу получения мультипотентных клеток млекопитающего. Клетки согласно изобретению способны дифференцироваться в несколько эндодермальных клеточных линий. Они получены из ткани желчных путей и являются позитивными по меньшей мере по одному поверхностному маркеру стволовых клеток, а именно EpCAM, N-CAM, CXCR4 или CD133, а также по меньшей мере одному маркеру линии панкреатических клеток, по меньшей мере одному маркеру линии печёночных клеток и по меньшей мере одному маркеру линии эндодермальных клеток. Настоящее изобретение позволяет создать альтернативные и дополнительные источники трансплантируемых, функциональных стволовых клеток и клеток-предшественников для применения в клинике. 2 н. и 20 з.п. ф-лы, 59 ил., 7 пр.

СПОСОБ ТРАНСПЛАНТАЦИИ КЛЕТОК ИЗ ПЛОТНЫХ ТКАНЕЙ

... 1. Способ трансплантации клеток внутреннего органа субъекту, имеющему внутренний орган в поврежденном или дисфункциональном состоянии, включающий:а. получение нормальных клеток внутреннего органа донора;b. комбинирование клеток с одним или несколькими гель-образующими биоматериалами для образования смеси;с. при необходимости комбинирование смеси с питательной средой, сигнальными молекулами, белками внеклеточного матрикса или их комбинацией;d. введение смеси по пункту (b) субъекту, у которого основная часть клеток, введенных по пункту (d), размещается в или на по меньшей мере части внутреннего органа in vivo.2. Способ по п.1, в котором нормальные клетки представляют собой стволовые клетки, коммитированные клетки-предшественники или зрелые клетки.3. Способ по п.1, в котором внутренний орган представляет собой печень, легкие, кишка, кишечник, сердце, почки, желчные пути, щитовидную железу, тимус, мозг или поджелудочную железу.4. Способ по п.3, в котором внутренний орган представляет собой ...

Vernetzer für Hydrogele

Die Erfindung betrifft biokompatible Hydrogele und stellt neuartige peptidische Vernetzer in Form eines linearen Moleküls bereit, welches eine Molekülmasse von 3 bis etwa 60 kDa besitzt, zur Vernetzung von funktionalisierten Polymeren zu zwei- oder mehrkomponentigen Hydrogelen. Die Erfindung betrifft auch Verfahren zu Herstellung solcher neuartiger Vernetzer sowie neuartiger Hydrogele.

Microparticles

A microparticle which comprises an acid with two or more acid groups and an organic base. The microparticle may have a particle size of 0.5-10 microns, and a molar ratio of acid groups to basic groups of 0.6-1.4:1. The acid may comprise bis-aliphatic acid, brassylic acid, sebacic acid, azelaic acid or a bis-carboxylic fatty acid in which the terminal carboxylic acids are linked by a region which is hydrophobic. The acid groups may also be separated by a saturated or unsaturated aliphatic chain; or substituted saturated, or unsaturated aliphatic chain. The organic base may comprise an aliphatic amine or an aromatic amine having a basic character or other nitrogen-containing base, one or more of an alkylated amine and an alkylated polyamine, N-methylmorpholine, N,N-dimethylaminoethanol, 4-dimethylaminopyridine, imidazole, 1-methylamidazole poly(diallyldimethylammonium chloride) (PDAC), didecylmethylammonium chloride (DDAC), dodecyldipropylenetriamine (DDPT) and poly epsilon lysine. A medical ...

SYNTHETIC MATERIAL, THE ACCUMULATION, WHICH PROMOTES GROWTH AND THE ATTACHMENT OF EPITHELIUM CELLS, PROSTHETI DEVICE FOR SUBEPITHELIALEN IMPLANTATION AS WELL AS TREATED LENS

Cell culture article and screening

Method of engrafting cells from solid tissues

A method of repairing diseased or dysfunctional organs or of establishing a model system of a disease state is provided. For repairing diseased organs, the method involves engraftment of cells from healthy tissue of the diseased or dysfunctional organ admixed with gel-forming biomaterials and nutrient medium, signaling molecules and extracellular matrix components that can be made insoluble rapidly upon transplantation to form a graft. In this way, the graft mimics the complexity of the native microenvironment with a minimum number of components that allow transplantation of cells to successfully engraft, expand and then rebuild part or the entirety of the diseased or dysfunctional organ. In the case of using grafting methods for establishing a disease model, diseased cells may be transplanted in the biomaterials and into experimental hosts.

Neural microphysiological systems and methods of using the same

The present disclosure generally relates to a cell culturing system, and specifically to a three-dimensional cell culturing system for neuronal cells that promotes both structural and functional characteristics that mimic those of in vivo peripheral fibers, including cell myelination. Using a dual hydrogel construct and explants from neuronal cells, the present disclosure provides methods., devices, and systems for in vitro spatially-controlled, three-dimensional models that permit intra- and extra-cellular electrophysiological measurements and recordings. The three-dimensional hydrogel constructs allow for flexibility in incorporated cell types, geometric fabrication, and electrical manipulation, providing viable systems for culture, perturbation, and testing of biomimetic neural growth with physiologically-relevant results.

Improved crosslinked hyaluronan hydrogels for 3D cell culture

The present invention relates to a new method for treating or processing a cross-linked hyaluronan hydrogel prior to its use in applications involving three-dimensional cell culture. The invention also relates to cross-linked hyaluronan hydrogels prepared by such a method and to their use in 3D cell culture, stem cell/tissue engineering, drug discovery, toxicology testing, and broad cell biology applications.

Surface functionalization

This invention is in the field of surface modification. In particular, the invention relates to the surface modification of microfluidic devices to alter surface hydrophobicity characteristics.

HYDROGEL BIOMIMETIC FOR INVASIVE DISEASES

An extracellular biomimetic for assessing and analyzing cell invasion includes hydrogel matrix and a first peptide crosslinked to the hydrogel matrix, where the first peptide is responsive to a first substance released by diseased cells upon invasion into the biomimetic. The biomimetic further includes at least one modulating agent enabling cell invasion independent from said first substance. The hydrogel matrix can comprise hyaluronate modified with furanyl functional groups, and the modulating agent can be viscoelastic polymer forming reversible crosslinks within the hydrogel matrix. Examples of the viscoelastic polymer include methyl cellulose, or functionalized methyl cellulose, for example, with thiol functional groups. The first substance released by diseased cells is an enzyme, for example, matrix metalloproteinase (MMP). The biomimetic can be used for drug screening to identify compounds that reduce the invasion and viability of the diseased cells, for example, cells from the lung ...

BIOFUNCTIONALIZED HYDROGEL FOR CELL CULTURE

Provided are biomaterials useful for cell culture, method of preparation thereof, and use thereof. The present biomaterial comprises a crosslinkeded hydrogel and a peptide chemically attached to the hydrogel, wherein the peptide comprises a histidine-alanine-valine (HAV) sequence. In particular, the present biomaterial may be useful for culturing neurons, brain endothelial cells, and/or glial cells, supporting the formation of synaptically connected neural networks, and growing stem cell-derived organoids that more closely resemble human organs.

SYSTEMS AND METHODS FOR IMMOBILIZING EXTRACELLULAR MATRIX MATERIAL ON ORGAN ON CHIP, MULTILAYER MICROFLUIDICS MICRODEVICES, AND THREE-DIMENSIONAL CELL CULTURE SYSTEMS

The presently disclosed subject matter provides an approach to address the needs for microscale control in shaping the spacial geometry and microarchitecture of 3D collagen hydrogels. For example, the disclosed subject matter provides for compositions, methods, and systems employing N-sulfosuccinimidyl-6-(4'-azido-2'- nitro-phenylamino)hexanoate ("sulfo-SANPAH"), to prevent detachment of the hydrogel from the anchoring substrate due to cell-mediated contraction.

METHOD FOR ACHIEVING EPITHELIALIZATION OF SYNTHETIC LENSES

Synthetic surfaces such as surfaces of implantable prosthetic devices are modified to enhance their ability to support the growth, migration and attachment of epithelial cells. A surface modifier composition 1 covalently bound to the synthetic surface, and an epithelial cell-supporting coating is applied to the modified surface. The surface modifier composition may also include an epithelial cell-supporting material. The invention is particularly suited towards the modification of synthetic epikeratophakia lenses.

METHOD FOR ACHIEVING EPITHELIALIZATION OF SYNTHETIC LENSES

Synthetic surfaces such as surfaces of implantable prosthetic devices are modified to enhance their ability to support the growth, migration and attachment of epithelial cells. A surface modifier composition is covalently bound to the synthetic surface, and an epithelial cell-supporting coating is applied to the modified surface. The surface modifier composition may also include an epithelial cell-supporting material. The invention is particularly suited towards the modification of synthetic epikeratophakia lenses.

Particle-containing cell aggregate

Disclosed is a particle-containing cell aggregate composed of cells and hydrogel particles, which are obtained by forming chemical crosslinks between one or more water-soluble synthetic polymers selected from among water-soluble synthetic polymers, polysaccharides and proteins. Also disclosed is a method for producing said cell aggregate.

Kit and method for promoting mesenchymal stem cell differentiation

The present invention is related to a kit comprising: (a) a mesenchymal stem cell; (b) a gelatin-hyaluronan-chondroitin tri-copolymer scaffold; (c) a kartogenin; and (d) a bioreactor. The present invention is also related to a method for promoting mesenchymal stem cell differentiating into cartilaginous tissue comprising: (a) incubating a mesenchymal stem cell in a gelatin-hyaluronan-chondroitin tri-copolymer scaffold in a presence of a kartogenin; and (b) incubating the mesenchymal stem cell and the tri-copolymer scaffold in a bioreactor.

GROWTH MATRICES FOR STEM CELL PROPAGATION IN VITRO AND IN TISSUE REGENERATION

The present invention provides a multifunctional 2-D and 3-D matrix for propagation of stein cells, in particular, a cliitosatv-based biomaieria! scaffold is engineered to promote CNS regeneration from primitive neural precursors by stabilizing a recombinant protein, fibroblast growth factor to preserve the cardinal properties of stem cells. The matrix, is further modified by the addition of either the extracellular matrix protein fibronectiii or the small peptide RGD or IK.VAV. A method to manu&eture an injectable multifunctional microsphere scaffold is also disclosed that is suitable as a vehicle for cell transplantation to repair traumatic brain injuries.

HYBRID MATRIX

The present invention relates to poly(caprolactone)-oligonucleotide surfaces for cell ware, and methods of use thereof for culturing, and differentiating cells.

Manufacturing process for polysaccharide beads

The invention discloses a method of manufacturing polysaccharide beads, comprising the steps of: i) providing a water phase comprising an aqueous solution of a polysaccharide; ii) providing an oil phase comprising at least one water-immiscible organic solvent and at least one oil-soluble emulsifier; iii) emulsifying the water phase in the oil phase to form a water-in-oil (w/o) emulsion; and iv) inducing solidification of the water phase in the w/o emulsion, wherein the organic solvent is an aliphatic or alicyclic ketone or ether.

HIGHLY FLEXIBLE DEGRADABLE FIBERS

The present invention relates to a method for producing biodegradable fibers on the basis of a silane compound, said silane compound being crosslinked during production and, at least to some extent, an organic acid being incorporated into the forming crosslinked structure via covalent bonds and/or contributing to the crosslinking. The present invention also relates to the fibers that can be produced by the method according to the invention and to the use thereof.

Proteinase-free coatings for colony passaging

A cell culture article includes a substrate having a polymer coating that is conducive to colony passaging of cells cultured on the coating. Example polymer coatings are formed from polygalacturonic acid (PGA), alginate, or combinations thereof. Cells cultured on the polymer coating can be separated from the substrate as a colony or layer of cells by exposing the polymer coating to (i) a chelating agent, (ii) a proteinase-free enzyme, or (iii) a chelating agent and a proteinase-free enzyme.

METHOD FOR PREPARING A DEGRADABLE POLYMER NETWORK

細胞培養製品およびスクリーニング

... 細胞と共にインキュベートするための合成ポリマー層を備えた細胞培養製品を生産する方法は、1種類以上の(メタ)アクリレート・モノマーを溶媒に希釈し、前記希釈したモノマーを細胞培養製品の表面に分散する各工程を有してなる。ある程度または実質的にすべての溶媒を除去した後、製品の表面でモノマーを重合し、製品の表面に付着した合成ポリマー層を形成する。 ...

肝外胆樹からの多能性幹細胞およびそれらを単離する方法

МУЛЬТИПОТЕНТНЫЕ СТВОЛОВЫЕ КЛЕТКИ ВНЕПЕЧЁНОЧНЫХ ЖЕЛЧНЫХ ПУТЕЙ И СПОСОБЫ ИХ ВЫДЕЛЕНИЯ

SYNTHETISCHES MATERIAL, DAS DIE ANLAGERUNG, DAS WACHSTUM UND DIE BEFESTIGUNG VON EPITHELZELLEN FÖRDERT, PROSTHETISCHE VORRICHTUNG ZUR SUBEPITHELIALEN IMPLANTATION SOWIE BEHANDELTE LINSE

Fibrosis model on a chip

Lung disease models on a chip

The presently disclosed subject matter provides a biomimetic lung disease model, and methods of its production and use. In one exemplary embodiment, the biomimetic lung disease model can include a first and second microchannel with a membrane coated with airway epithelial cells disposed between the microchannels and at least one device coupled to the biomimetic model that delivers an agent to at least one microchannel. In certain embodiments, the agent is cigarette smoke ...

SYNTHETIC SURFACES FOR THE CULTIVATION OF CELLS IN CHEMICALLY DEFINED MEDIA

Extracellular matrix - synthetic skin scaffold

The present invention provides a process or preparing an extracellular matrix composition which comprises: (a) mixing an aqueous solution of fibrinogen with a coagulating agent and a bulking agent and a foaming agent; (b) causing the mixture to foam and coagulate; (c) incubating the mixture obtained in step (b) with a cross-linking agent; and (d) washing the cross-linked composition obtained in step (c) to remove the cross-linking agent. Wherein the foaming agent consists of or comprises one or more surfactant agent(s) from the class of sugar-surfactants. The invention also relates to the formulation mixture as such, and to the products of the process.

Fibrosis model on a chip

The presently disclosed subject matter provides a biomimetic organ model, and methods of its production and use. In one exemplary embodiment, the biomimetic organ model can be a multi-layer model including a at least two microchannels and at least one chamber slab with at least one membrane coated with cells disposed between at least one microchannel and the at least one chamber slab. In another exemplary embodiment, the biomimetic organ disease model can be a five- layer model including a first and second microchannel with a membrane-gel layer- membrane coated or encompassing cells disposed between the microchannels. In certain embodiments, at least one device can be coupled to the biomimetic organ model that delivers an agent to at least one microchannel.

Hydrogel precursor formulation and the use thereof

The present invention relates to a hydrogel precursor formulation which is in the form of an unreacted powder. It comprises an activating enzyme, preferably thrombin, a cross-linking enzyme, preferably a transglutaminase, more preferably factor XIII transglutaminase, wherein the cross-linking enzyme is activatable by the activating enzyme in water with or without a buffer, and at least one structural compound A. Said structural compound is crosslinkable by a selective reaction mediated by the crosslinking enzyme to form a hydrogel, wherein the cross-linking enzyme is activated.

Devices and methods for delivering therapeutics

Disclosed herein are devices, methods, and compositions for delivering a therapeutic, e.g., a cell or a therapeutic agent. Disclosed is a device comprising a membrane and a population of non-native pancreatic β cells, wherein said non-native pancreatic β cells exhibit an in vitro glucose-stimulated insulin secretion (GSIS) response to a glucose challenge. Disclosed is a method of treating a condition comprising: placing a device disclosed herein in a subject in need thereof In some cases, said device is configured to remain in said subject for a period of more than six months, said condition is a chronic disease. In some cases, said chronic disease is diabetes.

Materials and methods for eliciting targeted antibody responses in vivo

Methods for generating and identifying antibodies specifically binding target molecules expressed by cells embedded in a three-dimensional extracellular matrix resembling the ...

Multipotent stem cells from the extrahepatic billary tree and methods of isolating same

The present invention relates to a multipotent stem cell, multipotent cell populations, and an enriched multipotent cell population, each found in fetal, neonatal, pediatric, and adult biliary tree tissue and up to 72 hours post mortem (although preferentially, within 10 hours post mortem) and capable of maturing into multiple endodermal tissues that include liver, biliary and pancreatic tissues. The multipotent stem/progenitor cell and cell populations are found in peribiliary glands, and progenitors descending from them are present throughout the biliary tree including in the gallbladder. High numbers of the peribiliary glands are found in the branching locations of the biliary tree such as hilum, common hepatic duct, cystic duct, common duct, common hepato-pancreatic duct and gallbladder. Related multipotent cells, multipotent cell populations and their descendent progenitors are found throughout the biliary tree including in the gall bladder, which does not have peribiliary glands.

HYDROGEL-BASED VASCULAR LINEAGE CELL GROWTH MEDIA AND USES THEREOF

A medium for growing vascular lineage cells is described. The vascular lineage cell growth medium includes an oligosaccharide-based hydrogel and a growth factor that promotes vascularization by vascular lineage cells.

METHOD FOR PREPARING A DEGRADABLE POLYMER NETWORK

The present invention relates to methods for preparing a degradable polymer network. The methods for preparing a degradable polymer network comprise a) preparing a polymer composition comprising monomers of cyclic carbonates and/or cyclic esters and/or linear carbonates and/or linear esters and/or cyclic ethers and/or linear hydroxycarboxylic acids at a temperature between 20°C and 200 °C; b) adding a cross-linking reagent comprising at least one double or triple C-C bond and/or a cross-linking radical initiator; c) processing the polymer composition (that contains the crosslinking reagentj into a desired shape; d) Crosslinking by irradiating the mixture. Further, the present invention relates to a degradable polymer network. Furthermore, the present invention relates to the use of the degradable polymer network.

STIMULI RESPONSIVE NANOFIBERS

A stimuli responsive nanofiber that includes a stimuli responsive polymer , such as a thermally responsive polymer, and a cross-linking agent having a t least two latent reactive activatable groups. The nanofiber may also inclu de a biologically active material or a functional polymer. The stimuli respo nsive nanofiber can be used to modify the surface of a substrate. When the n anofiber includes a thermally responsive polymer, the physical properties of the surface can be controlled by controlling the temperature of the system, thus controlling the ability of the surface to bind to a biologically activ e material of interest.

MATRIX AS A BALL AS CELL SUPPORTING

L'invention concerne une matrice en forme de bille comprenant du fibrinogène réticulé, la matrice étant exempte de fibrine, ainsi qu'un procédé de préparation d'une telle matrice comprenant les étapes suivantes : (a) la fourniture d'une composition initiale comprenant du fibrinogène et un facteur plaquettaire, (b) l'introduction de ladite composition initiale dans une huile chauffée à une température comprise entre 50 et 80°C de sorte à former une émulsion, (c) e mélange de l'émulsion ainsi obtenue à une température comprise entre 50 et 80°C jusqu'à l'obtention d'une matrice sous forme de bille, et (d) l'isolement de la matrice ainsi obtenue. La matrice est utilisée comme support cellulaire.

artigo de cultura celular e triagem

MULTIPOTENT STEM CELLS FROM THE EXTRAHEPATIC BILLARY TREE AND METHODS OF ISOLATING SAME

Multipotent stem cells from the extrahepatic biliary tree and methods of isolating same

The present invention relates to a multipotent stem cell, multipotent cell populations, and an enriched multipotent cell population, each found in fetal, neonatal, pediatric, and adult biliary tree tissue and up to 72 hours post mortem (although preferentially, within 10 hours post mortem) and capable of maturing into multiple endodermal tissues that include liver, biliary and pancreatic tissues. The multipotent stem/progenitor cell and cell populations are found in peribiliary glands, and progenitors descending from them are present throughout the biliary tree including in the gallbladder. High numbers of the peribiliary glands are found in the branching locations of the biliary tree such as hilum, common hepatic duct, cystic duct, common duct, common hepato-pancreatic duct and gallbladder. Related multipotent cells, multipotent cell populations and their descendent progenitors are found throughout the biliary tree including in the gall bladder, which does not have peribiliary glands.

CLEAVABLE CELLULOSIC SPONGE DEVELOPMENT FOR 3 DIMENSIONAL CELL CULTURE AND SPHEROIDS RETRIEVAL

A method of making a scaffold for 3 dimensional cell culture comprising the steps of conjugating a reducible disulfide bond onto a hydroxyl group at the side chain of a hydroxypropyl cellulose; forming a matrix of hydroxypropyl cellulose having the reducible disulfide bond conjugated onto the hydroxyl group such that a reducible disulfide bond exists adjacent to a double bond for crosslinking the matrix of hydroxypropyl cellulose. The scaffold and a system of using the scaffold for culturing 3 dimensional cell spheroids ...

Biocompatible smart responsive scaffold having interconnected pores

A polymeric scaffold contains pendant liquid crystal side chains and has fully interconnected pores. Such a polymeric scaffold will preferably be 3D in nature and elastomeric, biocompatible and biodegradable. Such 3D liquid crystal elastomer (LCE) scaffolds can be used for various biomedical applications, including cell culture applications. A method for the production of such a polymeric scaffold containing liquid crystals and having interconnected pores is also disclosed that uses a metal foam sacrificial template as a scaffold to produce the polymeric smart response scaffold of the present invention. Consistent and controlled pore sizes result from etching the sacrificial metal foam template away from the polymeric scaffold, permitting the incorporation of growth factors, when needed, for enhancing cell viability and proliferation.

METHOD FOR MANUFACTURING CELL MASS

A method for manufacturing a cell mass adherently cultured on a cell culture substrate, in which the cell culture substrate comprises two regions (A) and (B), and the method comprising steps (1) to (3): (A) an island-shaped region having a cell proliferation property and an area of 0.001 to 1 mm2; and (B) a region adjacent to the region (A) and having no cell proliferation properties, (1) a step of preparing a cell suspension comprising a mesenchymal cell and an ectoderm-derived cell; (2) a step of bringing the cell suspension into contact with the cell culture substrate, and randomly adhering the two types of cells to the region (A), and in which, on the contact surface between the cell suspension and the cell culture substrate, a total number of cells of the two types of cells is 100 to 100,000 cells/cm2; and (3) a step of culturing the cell adhered to the region (A) and forming a cell mass comprising the two types of cells.

3D Bioprinter That Cures Hydrogel Via Visible Light

A 3D bioprinter having a visible light source to photocure biomaterial is disclosed. The 3D bioprinter prints visible light-curable biomaterial along with viable cells, and visible light photocures the biomaterial while maintaining cell viability. Visible light 3D bioprinter systems and methods of printing are further disclosed.

СПОСОБ ПРИВИВКИ КЛЕТОК ПЕЧЕНИ СУБЪЕКТУ С ЗАБОЛЕВАНИЕМ ИЛИ ДИСФУНКЦИЕЙ ПЕЧЕНИ

Lung disease models on a chip

Systems and methods for immobilizing extracellular matrix material on organ on chip, multilayer microfluidics microdevices, and three-dimensional cell culture

A method of fabricating a microengineered perfusable lumen comprising fabricating a microchannel in a first body which forms a substrate for tissue growth, injecting the microchannel with a heterobifunctional crosslinker, and curing the heterobifunctional crosslinker. A four-sided microchannel having three different sides treated with the heterobifunctional crosslinker is formed, and the microchannel is injected with an extracellular matrix (ECM) gel layer embedded with a contractile tissue. The cell-mediated contractile forces shape the tissue geometry as the gel layer contracts between the fixed anchorage points. Preferably the microchannel is formed using photolithography. Preferably the substrate is polydimethylsiloxane (PDMS) and the heterobifunctional crosslinker is N-sulfosuccinimidyl-6-(4’-azido-2’- nitro-phenylamino)hexanoate (sulpho-SANPAH). The ECM gel layer may comprise extracellular matrix proteins selected from collagen, fibronectin, laminin and/or hyaluronic acid. The contractile ...

Adipose tissue matrices

The present disclosure provides tissue products produced from adipose tissues, as well as methods for producing such tissue products. The tissue products can include acellular extracellular matrices. In addition, the present disclosure provides systems and methods for using such products.

Method for preparing a degradable polymer network

The present invention relates to methods for preparing a degradable polymer network. The methods for preparing a degradable polymer network comprise a) preparing a polymer composition comprising monomers of cyclic carbonates and/or cyclic esters and/or linear carbonates and/or linear esters and/or cyclic ethers and/or linear hydroxycarboxylic acids at a temperature between 20°C and 200 °C; b) adding a cross-linking reagent comprising at least one double or triple C-C bond and/or a cross-linking radical initiator; c) processing the polymer composition (that contains the crosslinking reagentj into a desired shape; d) Crosslinking by irradiating the mixture. Further, the present invention relates to a degradable polymer network. Furthermore, the present invention relates to the use of the degradable polymer network.

Polymer-based material having covalently bonded, enzymatically degradable peptide sequences

The invention relates to a polymer-based material having covalently bonded enzymatically degradable peptide sequences which are not degradable by the biological and metabolic activity of cells and tissues, wherein the peptide sequences each consist of two to fifteen amino acids and are incorporated into the polymer-based material or conjugated onto the polymer-based material. The peptide sequence can accordingly either be part of a three-dimensional or two-dimensional structure of the polymer-based material. By means of an enzyme-addition-controlled degradation of a covalent bond in the peptide sequence either a bioorthogonal degradation of the three-dimensional structure, or in the case of a conjugation of the peptide sequence onto the polymer-based material the liberation of at least a part of the molecule, is effected. The invention further relates to the use of such a polymer-based material for an ...

Polymer-based material having covalently bonded, enzymatically degradable peptide sequences

The invention relates to a polymer-based material having covalently bonded enzymatically degradable peptide sequences which are not degradable by the biological and metabolic activity of cells and tissues, wherein the peptide sequences each consist of two to fifteen amino acids and are incorporated into the polymer-based material or conjugated onto the polymer-based material. The peptide sequence can accordingly either be part of a three-dimensional or two-dimensional structure of the polymer-based material. By means of an enzyme-addition-controlled degradation of a covalent bond in the peptide sequence either a bioorthogonal degradation of the three-dimensional structure, or in the case of a conjugation of the peptide sequence onto the polymer-based material the liberation of at least a part of the molecule, is effected. The invention further relates to the use of such a polymer-based material for an ...

METHODS TO GENERATE POLYMER SCAFFOLDS HAVING A GRADIENT OF CROSSLINKING DENSITY

The present invention is directed to a method of making a live cell construct or a support, comprising: (a) providing a non-cellular organic polymer support having a top surface, a bottom surface, and an intermediate portion there between, and (b) contacting a cross-linking agent to one surface of said support for a time sufficient to generate a gradient of cross-linking of said polymer in said intermediate portion. Also provided are live cell constructs, supports, and methods of use of the supports and live cell constructs.

SURFACE FUNCTIONALIZATION

CA 3069742 Abstract The invention pertains to methods of functionalizing the surface of an enclosed microfluidic channel. The methods comprise exposing a portion of an unmodified surface of the microfluidic channel to a bifunctional crosslinker, activating said crosslinker to create a crosslinked surface, and exposing the crosslinked surface of a surface hydrophobicity modifying molecule to create a functionalized surface. Date Recue/Date Received 2021-01-08 ...

ENCAPSULATED LIVER TISSUE

The present disclosure provides an encapsulated liver tissue that can be used in vivo to improve liver functions, in vitro to determine the hepatic metabolism and/or hepatotoxicity of an agent and ex vivo to remove toxic compounds from patients' biological fluid. The encapsulated liver tissue comprises at least one liver organoid at least partially covered with a biocompatible cross-linked polymer. Processes for making the encapsulated liver tissue are also provided.

A NANOFIBRILLAR CELLULOSE PRODUCT AND A METHOD FOR MANUFACTURING THEREOF

The present application provides a method for preparing nanofibrillar cellulose product, the method comprising providing nanofibrillar cellulose, providing multivalent cations, contacting the nanofibrillar cellulose with the multivalent cations, and allowing reacting for a period of time to obtain cross-linked nanofibrillar cellulose product. The present application also provides a nanofibrillar cellulose product comprising nanofibrillar cellulose and multivalent cations, wherein the nanofibrillar cellulose is crosslinked by the multivalent cations.

LUNG DISEASE MODELS ON A CHIP

The presently disclosed subject matter provides a biomimetic lung disease model, and methods of its production and use. In one exemplary embodiment, the biomimetic lung disease model can include a first and second microchannel with a membrane coated with airway epithelial cells disposed between the microchannels and at least one device coupled to the biomimetic model that delivers an agent to at least one microchannel. In certain embodiments, the agent is cigarette smoke.

COMPOSITIONS AND METHODS OF USING LIVING AND NON-LIVING BIOACTIVE DEVICES WITH COMPONENTS DERIVED FROM SELF- RENEWING COLONY FORMING CELLS CULTURED AND EXPANDED IN VITRO

The invention relates to methods and uses of cells for the prevention and treatment of a wide variety of diseases and disorders and the repair and regeneration of tissues and organs using low passage and extensively passaged in vitro cultured, self-renewing, colony forming somatic cells (CF-SC). For example, adult bone marrow-derived somatic cells (ABM-SC), or compositions produced by such cells, are useful alone or in combination with other components for treating, for example, cardiovascular, neurological, integumentary, dermatological, periodontal, and immune mediated diseases, disorders, pathologies, and injuries.

MULTIPOTENTIAL CELLS MOTHER OF THE EXTRAHEPATIC BILIARY TREE AND METHODS OF ISOLATION OF THE SAME

Una célula madre multipotencial, poblaciones de células multipotenciales y una poblacion de células multipotenciales enriquecida, cada una presente en el tejido biliar fetal, neonatal, pediátrico y de adultos y hasta 72 horas de post-mortem (aunque con preferencia dentro de las 10 horas de post-mortem) y con capacidad de madurar en multiples tejidos endodérmicos que incluyen los tejidos hepáticos, biliares y pancreáticos. La célula madre/progenitora multipotencial y las poblaciones de células se encuentran en las glándulas peribiliares, y la progenie descendiente de las mismas está presente en todo el árbol biliar, inclusive en la vesícula biliar. Existe una gran cantidad de glándulas peribiliares en las ubicaciones ramificadas del árbol biliar tal como el hilio, el dueto hepático comun, el dueto cístico, el dueto comun, el dueto hepato-pancreático comun y la vesícula biliar. Hay células multipotenciales relacionadas, poblaciones de células multipotenciales y sus progenitores descendientes ...

SYSTEM AND METHOD FOR MAGNETIC SELF-ASSEMBLY

METHOD AND MATERIAL FOR DIFFERENTIATED SEQUESTRATION OF SUBSTANCES OF DIFFERENT SUBSTANCE GROUPS WITH THE AID OF HYDROGELS CONTAINING SULPHATED OR SULPHONATED COMPONENTS

A method is disclosed for the differentiated sequestration of substances of different substance groups A and B in a sulfated and/or sulfonated hydrogel while simultaneously releasing substances of substance group A or B from the sulfated and/or sulfonated hydrogel into the biofluid. The sulfated and/or sulfonated hydrogel is selected from a group of hydrogels of Type 1, 2, 3, 4 and consist of uncharged and charged components. The charged components are characterized by calculating the number of sulfated or sulfonated groups per repeat unit divided by the molecular mass of the repeat unit, for each of Type 1 2 3 and 4. The swollen hydrogels have a concentration of sulfated or sulfonated groups in mmol/ml for Type 1, Type 2, Type 3 and Type 4. The concentration of substances of each substance group A and group B in the biofluid is influenced by the selection of the type of hydrogel. 137.-. (canceled)38. A method for differentiated sequestration of substances of different substance groups in a sulfated and/or sulfonated hydrogel comprising:sequestration of substances of groups A and B and depletion of substances of a group A from a biofluid with simultaneous differentiated release of substances of group A or B from the sulfated and/or sulfonated hydrogel into the biofluid or the reduced binding of substances of group B in the sulfated and/or sulfonated hydrogel,wherein the sulfated and/or sulfonated hydrogel include type 1, type 2, type 3 and type 4 hydrogels and the hydrogels are composed of uncharged building blocks (UGB) and charged building blocks (GB),calculating a parameter of the charged building blocks from the number of sulfate and/or sulfonate groups per repeat unit divided by the molar mass of the repeat unit of 0.0040-0.0060 mole/g for type 1, of 0.0025-0.0040 mole/g for type 2, of 0.0005-0.0025 mole/g for type 3, and of 0040 to 0.0100 mole/g for type 4, wherein swollen hydrogels have a storage module of less than 20 kPa and the swollen hydrogels have a ...

ADHESIVE CELL TISSUE GELS

Described herein is a cell tissue gel cross-linked with a cross-linking agent, and a quenching agent bound to a reactive group of the cross-linking agent.

SURFACE FUNCTIONALIZATION

This invention is in the field of surface modification. In particular, the invention relates to the surface modification of microfluidic devices to alter surface hydrophobicity characteristics.

DISSOLVABLE MICROCARRIERS FOR CULTURING CELLS AND RELATED METHODS

CELL ATTACHMENT MATERIALS, DEVICES AND USES THEREOF

СПОСОБ ПРИВИВКИ КЛЕТОК ПЕЧЕНИ СУБЪЕКТУ С ЗАБОЛЕВАНИЕМ ИЛИ ДИСФУНКЦИЕЙ ПЕЧЕНИ

Группа изобретений относится к медицине, а именно к трансплантологии, и может быть использована для трансплантации клеток печени субъекту, имеющему заболевание или дисфункцию печени. Для этого непосредственно в или на печень субъекта вводят смесь, содержащую клетки печени и один или несколько биоматериалов, полученных из модифицированной тиолом карбоксиметил НА (CMHA-S), причем клетки печени содержат одну или несколько комбинаций одной или нескольких эпителиальных клеток и одного или нескольких из мезенхимальных линейных клеточных партнеров. Также предложен способ введения в или на печень субъекта смеси, содержащей клетки печени и один или несколько биоматериалов, причем клетки печени содержат один или несколько предшественников клеток печени, и по меньшей мере один или несколько биоматериалов произведены из модифицированной тиолом карбоксиметил НА (CMHA-S), при этом смесь получают как гидрогель, содержащий клетки, смешивая CMHA-S, полиэтиленгликольдиакрилат (PEG-DA) и клетки с последующим ...

Kationisierte, proteinbasierte, makroporöse Gerüststrukturen und deren Verwendung zur Kultivierung von Zellen

Die vorliegende Erfindung betrifft eine dreidimensionale makroporöse Gerüststruktur, umfassend vernetztes kationisiertes Rinderserumalbumin. Weiterhin betrifft die vorliegende Erfindung ein Herstellungsverfahren für die dreidimensionale makroporöse Gerüststruktur, ein Verfahren zur Kultivierung von Zellen in der dreidimensionalen makroporösen Gerüststruktur und ein Kit, das die vorstehende dreidimensionale makroporöse Gerüststruktur umfasst.

Method for stem cell culture and cells derived therefrom

Fibrosis model on a chip

Compositions and methods of cell attachment

Systems and methods for immobilizing extracellular matrix material on organ on chip, multilayer microfluidics microdevices, and three-dimensional cell culture

Matrix in ball form as a cell carrier

The invention relates to a matrix in ball form comprising cross-linked fibrinogen, the matrix being free from fibrin, as well as to a method for preparing such a matrix, comprising the following steps: (a) providing an initial composition comprising fibrinogen and a platelet factor, (b) injecting said initial composition into an oil heated to a temperature of 50 °C to 80 °C so as to form an emulsion, (c) mixing the emulsion thus obtained at a temperature of 50 °C to 80 °C until a matrix in ball form is obtained, and (d) isolating the matrix thus obtained. The matrix is used as a cell carrier.

Phase separated composite

A composite is disclosed. The composite comprises a first conjugate of a polymer and a first phenol-containing moiety, and a second conjugate of a gelatin or collagen and a second phenol-containing moiety, wherein the polymer is selected so that the first conjugate is less cell-adhesive than the second conjugate, at least one of the first and second conjugates is crosslinked to form a matrix, and the composite comprises discrete regions that are rich in one of said first and second conjugates. A method of forming such composite is also disclosed. The method comprises mixing precursors for the first and second conjugates in a solution for forming said composite, and dispersing a catalyst in the solution to catalyze crosslinking of at least one of the first and second conjugates to form the matrix. The composite may be used to grow cells.

Method for Preparing a Degradable Polymer Network

The present invention relates to methods for preparing a degradable polymer network. The methods for preparing a degradable polymer network comprise a) preparing a polymer composition comprising monomers of cyclic carbonates and/or cyclic esters and/or linear carbonates and/or linear esters and/or cyclic ethers and/or linear hydroxycarboxylic acids at a temperature between 20° C. and 200° C.; b) adding a cross-linking reagent comprising at least one double or triple C—C bond and/or a cross-linking radical initiator; c) processing the polymer composition (that contains the crosslinking reagentj into a desired shape; d) Crosslinking by irradiating the mixture. Further, the present invention relates to a degradable polymer network. Furthermore, the present invention relates to the use of the degradable polymer network.

Thermally Induced Gelation Of Collagen Hydrogel And Method Of Thermally Inducing Gelling A Collagen Hydrogel

The present invention relates to collagen hydrogels. Particularly, the invention relates to hydrogels comprising a telopeptide collagen (“telo-collagen”) and an atelopeptide collagen (“atelo-collagen”); hydrogels comprising collagen and chitosan; methods of making the hydrogels; methods of reducing gelation of a hydrogel mixture at room temperature; methods of reducing compaction of cells; and methods of culturing cells on such hydrogels.

Stimuli Responsive Nanofibers

A stimuli responsive nanofiber that includes a stimuli responsive polymer, such as a thermally responsive polymer, and a cross-linking agent having at least two latent reactive activatable groups. The nanofiber may also include a biologically active material or a functional polymer. The stimuli responsive nanofiber can be used to modify the surface of a substrate. When the nanofiber includes a thermally responsive polymer, the physical properties of the surface can be controlled by controlling the temperature of the system, thus controlling the ability of the surface to bind to a biologically active material of interest.

HOLLOW CELLULAR MICROFIBRE AND METHOD FOR PRODUCING SUCH A HOLLOW CELLULAR MICROFIBRE

The invention relates to a hollow cell microfibre comprising successively, organized around a lumen, at least one endothelial cell layer, at least one smooth muscle cell layer, an extracellular matrix layer, and optionally an outer hydrogel layer. The invention also relates to a process for fabricating such a hollow cell microfibre. 116-. (canceled)17. An artificial hollow cell microfibre comprising successively , organized around a lumen:at least one endothelial cell layer;at least one smooth muscle cell layer;an extracellular matrix layer; and optionallyan outer hydrogel layer.18. The artificial hollow cell microfibre according to claim 17 , wherein the outer hydrogel layer is present and comprises alginate.19. The artificial hollow cell microfibre according to claim 17 , wherein the ratio in cmof endothelial cells to smooth muscle cells in the hollow cell microfibre is between 3:1 and 2:1.20. The artificial hollow cell microfibre according to claim 17 , wherein the endothelial cells are selected from the groip consisting in mammalian umbilical vein endothelial cells (UVEC) claim 17 , dermal microvascular endothelial cells (DMEC) claim 17 , dermal blood endothelial cells (DBEC) claim 17 , dermal lymphatic endothelial cells (DLEC) claim 17 , cardiac mirovascular endothelial cells (CMEC) claim 17 , pulmonary microvascular endothelial cells (PMEC) and uterine microvascular endothelial cells (UtMEC).21. The artificial hollow cell microfibre according to claim 17 , wherein the smooth muscle cells are selected from the group consisting in mammalian vascular smooth muscle cells claim 17 , lymphatic smooth muscle cells claim 17 , digestive tract smooth muscle cells claim 17 , bronchial smooth muscle cells claim 17 , kidney smooth muscle cells claim 17 , bladder smooth muscle cells claim 17 , dermal smooth muscle cells claim 17 , uterine smooth muscle cells and ciliary smooth muscle cells.22. The artificial hollow cell microfibre according to claim 17 , wherein the ...

System and Method for a Piezoelectric Collagen Scaffold

The present invention provides novel methods for poling piezoelectric materials, e.g., collagen, which are carried out in the absence of liquid media and at a relatively low temperature. The present invention also provides electroactive scaffolds comprising poled collagen for promoting cell growth and differentiation. 1. A method of poling piezoelectric material , said method comprising exposing said piezoelectric material to a constant electric field;wherein said method is carried out at a temperature of about 80° C. or less.2. The method of claim 2 , wherein said method is carried out in the absence of a liquid medium.3. The method of claim 1 , wherein said method is carried out at a temperature of about 25° C. to about 80° C.4. The method of claim 3 , wherein said method is carried out at a temperature of about 50° C.5. The method of claim 1 , wherein said method comprises exposing said piezoelectric material to a constant electric field of about 0.5×10to about 10V/m.6. The method of claim 1 , wherein said method comprises exposing said piezoelectric material to a constant electric field of about 4.4×10V/m.7. The method of claim 1 , wherein said method comprises applying to the piezoelectric material an electric voltage of about 1 kV to about 50 kV.8. The method of claim 1 , wherein the piezoelectric material is sandwiched between Teflon and steel plates during exposure to the constant electric field.9. The method of claim 1 , wherein the piezoelectric material comprises a polymer.10. The method of claim 9 , wherein said polymer is a naturally derived polymer.11. The method of claim 9 , wherein said polymer is biocompatible claim 9 , biodegradable or both.12. The method of claim 9 , wherein said polymer is selected from the group consisting of collagen claim 9 , gelatin claim 9 , zein claim 9 , elastin claim 9 , silk claim 9 , chitosan claim 9 , chitin claim 9 , alginate claim 9 , starch claim 9 , cellulose claim 9 , proteoglycans and a glycosaminoglycan.13. The ...

Hydrogel Comprising A Scaffold Macromer Crosslinked With A Peptide And A Recognition Motif

Methods of forming, dissolving, and functionalizing an extracellular matrix gel on demand based on cross-linking, modification, and dissolution of hydrogels using transpeptidase (e.g. sortase) are disclosed. Also provided are hydrogels comprising one or more macromers crosslinked to a mixture of peptides, wherein all or a portion of the peptides in the mixture comprise a recognition motif cleavable by a transpeptidase (e.g., sortase). 1. A hydrogel comprising one or more scaffold macromers crosslinked to a mixture of peptides , wherein all or a portion of the peptides in the mixture comprise a recognition motif cleavable by a transpeptidase.2. The hydrogel of claim 1 , wherein the transpeptidase is a sortase or a sortase variant.3. The hydrogel of claim 1 , wherein the recognition sequence comprises a motif selected from the group consisting of: LPXSG claim 1 , LPXTG claim 1 , and LAXTG.4. The hydrogel of any of claim 1 , wherein 0.001% to 80% of the peptides in the mixture comprise a recognition motif cleavable by a first transpeptidase.5. The hydrogel of claim 4 , wherein each peptide that comprises a first recognition sequence cleavable by the first transpeptidase does not comprise a second recognition motif cleavable by a second transpeptidase.6. The hydrogel of any of claim 1 , wherein the peptide further comprises a sequence cleavable by a protease.7. The hydrogel of claim 6 , wherein the protease is an endopeptidase or a metalloprotease.8. The hydrogel of claim 1 , wherein the peptide comprises the amino acid sequence GCRDLPRTGGPQGIWGQDRCG.9. The hydrogel of claim 1 , wherein a portion of the peptides in the mixture is crosslinked to a macromer at its N-terminus claim 1 , and is free at its C-terminus.10. The hydrogel of claim 1 , wherein the hydrogel encapsulates a cell claim 1 , a tissue claim 1 , or an organ.11. The hydrogel of claim 1 , wherein the scaffold macromer is selected from any one or more of polyethyleneglycol (PEG) claim 1 , a dextran claim 1 , ...

MATRIX IN BALL FORM AS A CELL CARRIER

The invention relates to a matrix in ball form comprising cross-linked fibrinogen, the matrix being free from fibrin, as well as to a method for preparing such a matrix, comprising the following steps: (a) providing an initial composition comprising fibrinogen and a platelet factor, (b) injecting said initial composition into an oil heated to a temperature of 50° C. to 80° C. so as to form an emulsion, (c) mixing the emulsion thus obtained at a temperature of 50° C. to 80° C. until a matrix in ball form is obtained, and (d) isolating the matrix thus obtained. The matrix is used as a cell carrier. 1. A matrix in ball form comprising cross-linked fibrinogen wherein the matrix is free from fibrin.2. The matrix according to claim 1 , wherein it is porous.3. The matrix according to claim 2 , wherein it has pores with a diameter smaller than 1 μm.4. The matrix according to claim 1 , wherein the fibrinogen is cross-linked via a platelet factor.5. The matrix according to claim 1 , wherein it has a diameter comprised between 20 μm and 2 mm claim 1 , in particular between 50 μm and 1000 μm.6. The matrix according to claim 1 , wherein it further comprises at least one bioactive agent such as a cell claim 1 , a protein claim 1 , for example a growth factor claim 1 , a medicinal product claim 1 , a hormone claim 1 , a cytokine or a combination thereof.7. The matrix according to claim 6 , wherein the protein is a growth factor such as IGF-1.8. The matrix according to claim 1 , on the surface of which cells are adhered.9. A method for preparing a matrix according to claim 1 , comprising the following steps:(a) providing an initial composition comprising fibrinogen and a platelet factor,(b) injecting said initial composition into an oil heated to a temperature of 50° C. to 80° C. so as to form an emulsion,(c) mixing the emulsion thus obtained at a temperature of 50° C. to 80° C. until a matrix in ball form is obtained, and(d) isolating the matrix thus obtained.10. The method ...

DEVICES AND METHODS FOR SINGLE CELL ANALYSIS

The present disclosure provides systems, methods, and devices for the simultaneous determination of a single cell's response to a stimuli and characterization of its cell response. The present disclosure further provides methods for detection of disease state, clinical management of a subject suffering from a disease, drug screening, prediction of drug response, and stands to help direct drug and diagnostic development for the treatment of disease. 1. (canceled)2. A method of agent transfer comprising:providing a plurality of cells from a biological sample comprising a heterogenous population of cells from a patient positioned on a surface of a first solid substrate at a plurality of cell-philic sites;immobilizing a portion of the cells in a hydrogel concentration at their respective cell-philic sites thereby creating a plurality of three-dimensional cell microenvironments comprising the hydrogel composition and the cells, the hydrogel composition of each three-dimensional cell microenvironment being sized and positioned so as to extend upward with a dome shape from the surface of the solid substrate;dispending an agent onto an agent transfer device comprising a plurality of agent transfer array elements positioned on a surface of a second solid substrate; andcontacting the plurality of agent transfer array elements to the plurality of three-dimensional cell microenvironments, such that each agent transfer array element corresponds to a three-dimensional cell microenvironment, wherein the contacting allows the agent to be transferred to the plurality of three-dimensional cell microenvironments,3. The method of claim 2 , wherein the agent transfer device transfers at least 50% of the original concentration of the agent on the agent transfer device to the plurality of three-dimensional cell microenvironments.4. The method of claim 2 , wherein the plurality of cells comprise a clinical sample.5. The method of claim 2 , wherein the plurality of cells comprise a tumor ...

METHOD FOR STEM CELL CULTURE AND CELLS DERIVED THEREFROM

There is described a method of promoting the attachment, survival and/or proliferation of a stem cell in culture, the method comprising culturing a stem cell on a positively-charged support surface. There are also provided a cell composition prepared according to the method of the invention. 1. A cell culture system comprising substantially undifferentiated stem cells cultured on a positively-charged support surface.2. The cell culture system of claim 1 , wherein the support surface comprises a positively-charged molecule bound thereto and wherein the positively charged molecule is tri-methylamine.3. The cell culture system of claim 1 , wherein the support surface is selected from the group consisting of a tissue culture plate claim 1 , a microscope slide claim 1 , a multi-well plate claim 1 , a flask claim 1 , a bottle claim 1 , a bioreactor claim 1 , a two- or three-dimensional scaffold claim 1 , a tube claim 1 , a suture claim 1 , a membrane claim 1 , a film claim 1 , a microcarrier bead claim 1 , a tissue and an organ.4. The cell culture system of claim 3 , wherein the support surface is the surface of a microcarrier bead.5. The cell culture system of claim 1 , further comprising an extracellular matrix component.6. The cell culture system of claim 5 , wherein the extracellular matrix component is selected from the group consisting of elastin claim 5 , fibronectin claim 5 , vitronectin claim 5 , tenascin claim 5 , laminin claim 5 , entactin claim 5 , aggrecan claim 5 , decorin claim 5 , collagen I claim 5 , collagen III claim 5 , collagen IV claim 5 , and collagen VI claim 5 , biologically active fragments or variants of said proteins claim 5 , or combinations thereof.7. The cell culture system of claim 1 , wherein the substantially undifferentiated stem cells are passaged and maintained as single-cell culture.8. The cell culture system of claim 1 , wherein the substantially undifferentiated stem cells are human stem cells.9. The cell culture system of claim 1 , ...

COMPOSITIONS AND METHODS OF CELL ATTACHMENT

Compositions, devices and methods are described for improving adhesion, attachment, and/or differentiation of cells in a microfluidic device or chip. In one embodiment, one or more ECM proteins are covalently coupled to the surface of a microchannel of a microfluidic device. The microfluidic devices can be stored or used immediately for culture and/or support of living cells such as mammalian cells, and/or for simulating a function of a tissue, e.g., a liver tissue, muscle tissue, etc. Extended adhesion and viability with sustained function over time is observed. 1. A method of culturing cells , comprising: a) providing a microfluidic device comprising a surface; b) covalently attaching one or more proteins or peptides to said surface at a selected area or pattern using a crosslinker so as to create a treated surface; c) seeding viable cells on said treated surface so as to create attached cells; and d) culturing said attached cells.2. The method of claim 1 , wherein said microfluidic device comprises a microchannel claim 1 , said surface disposed within said microchannel claim 1 , and wherein said microchannel is in fluidic communication with a fluidic source comprising fluid claim 1 , the method further comprising flowing fluid from said fluid source through said microchannel so as to create flow conditions claim 1 , and wherein culturing in d) further comprises culturing said attached cells under said flow conditions.3. The method of claim 1 , wherein said crosslinker comprises at least one light-reactive portion claim 1 , at least one chemically reactive portion.4. The method of claim 1 , wherein said crosslinker further comprises at least one spacer portion.5. The method of claim 3 , wherein said at least one light-reactive portion is selected from the group consisting of a nitrophenyl claim 3 , a diazirine and an azides.6. The method of claim 3 , wherein said at least one chemically reactive portion is selected from the group consisting of NHS-ester claim 3 , ...

Compositions and methods of cell attachment

Compositions, devices and methods are described for improving adhesion, attachment, and/or differentiation of cells in a microfluidic device or chip. In one embodiment, one or more ECM proteins are covalently coupled to the surface of a microchannel of a microfluidic device. The microfluidic devices can be stored or used immediately for culture and/or support of living cells such as mammalian cells, and/or for simulating a function of a tissue, e.g., a liver tissue, muscle tissue, etc. Extended adhesion and viability with sustained function over time is observed.

METHODS AND SYSTEMS FOR CELL AND BEAD PROCESSING

The present disclosure provides methods and systems for cell and bead processing or analysis. A method for processing a cell or bead may comprise subjecting a bead to conditions sufficient to change a first characteristic or set of characteristics (e.g., cell or bead size). Such a method may further comprise subjecting the cell or bead to conditions sufficient to change a second characteristic or set of characteristics. In some cases, crosslinks may be formed within the cell or bead. 182.-. (canceled)83. A method of processing a cell , comprising: (i) change a cross-section of said cell from a first cross-section to a second cross-section, which second cross-section is less than said first cross-section, and', '(ii) form crosslinks within said cell having said second cross-section; and, '(a) subjecting said cell to conditions sufficient to(b) providing said cell having said second cross-section in an aqueous fluid.84. The method of claim 83 , wherein said crosslinks are formed upon cross-linking one or more cross-linkable molecules within said cell.85. The method of claim 84 , wherein said one or more cross-linkable molecules are one or more polymers.86. The method of claim 83 , wherein said crosslinks are formed upon polymerizing a plurality of monomers within said cell.87. The method of claim 83 , wherein said cross-section of said cell is changed from said first cross-section to said second cross-section concurrently with formation of said crosslinks within said cell.88. The method of claim 83 , wherein said crosslinks are formed subsequent to changing said cross-section from said first cross-section to said second cross-section.89. The method of claim 83 , wherein said second cross-section is substantially maintained in said aqueous fluid.90. The method of claim 83 , wherein said aqueous fluid is in a droplet as part of an emulsion.91. The method of claim 90 , wherein the volume of said droplet is less than 10 claim 90 ,000 pL.92. The method of claim 83 , ...

MICROPARTICLES

The invention provides a self-assembled microparticle having an acid having two or more acid groups and an organic base in a solvent. The microparticles may form into a macrostructure and provide a scaffold for cell culture. The particle is of micron scale. The microparticle may be obtained by contacting a bis-acid and organic base in a hydrophilic solvent, wherein the acid is insoluble or sparingly soluble in the hydrophilic solvent and the organic base is soluble in a hydrophilic solvent. The microparticles have antimicrobial activity and may be used in a wide range of consumer product applications, cell culture and medical products, such as wound dressings. 1. A self-assembled microparticle comprising an acid having two or more acid groups and an organic base.2. A microparticle according to having a particle size of 0.5 to 10 microns.3. A microparticle according to in which the molar ratio of acid groups to basic groups in the acid and base is from 0.6 to 1.4:1.4. (canceled)5. A method of making a microparticle according to suitable for use as a particulate support comprising contacting a bis-acid and an organic base in a hydrophilic solvent claim 1 , wherein the acid is insoluble or sparingly soluble in the hydrophilic solvent and the organic base is soluble in a hydrophilic solvent.67-. (canceled)8. A microparticle according to wherein the acid comprises a bis-acid.911-. (canceled)12. A microparticle according to wherein the acid comprises a compound of general formula HOOC—(CH)—COOH wherein n is sufficiently large that the bis acid is sparingly soluble or insoluble in water.13. A microparticle according to wherein n is at least 5 and not more than 40.14. A microparticle according to wherein the acid comprises brassylic acid claim 1 , sebacic acid and/or azelaic acid.15. A microparticle according to wherein the organic base comprises an aliphatic amine or an aromatic amine having a basic character or other nitrogen-containing base.16. (canceled)17. A ...

THERMALLY RESPONSIVE CELL CULTURE SURFACES

A stimuli responsive nanofiber that includes a stimuli responsive polymer, such as a thermally responsive polymer, and a cross-linking agent having at least two latent reactive activatable groups. The nanofiber may also include a biologically active material or a functional polymer. The stimuli responsive nanofiber can be used to modify the surface of a substrate. When the nanofiber includes a thermally responsive polymer, the physical properties of the surface can be controlled by controlling the temperature of the system, thus controlling the ability of the surface to bind to a biologically active material of interest. 152.-. (canceled)53. A cell culture article comprising a surface and a coating composition in contact with the surface , the coating composition comprising:(a) a thermally responsive polymer, and(b) a monomeric or polymeric crosslinking agent having at least two latent photoreactive groups capable of forming covalent bonds when the coating composition is subjected to electromagnetic energy, thereby coupling the thermally responsive polymer to the surface of the cell culture article in a manner in which at least some of the latent photoreactive groups remain in an inactive state.54. The article according to wherein the latent photoreactive groups are capable of forming a covalent bond with the surface.55. The article according to wherein the covalent bond is formed by carbon or nitrogen bond insertion claim 54 , hydrogen abstraction followed by radical recombination claim 54 , or dimerization.56. The article according to wherein the latent photoreactive groups are aryl ketones.57. The article according to wherein the aryl ketones are selected from acetophenones claim 56 , benzophenones claim 56 , anthraquinones claim 56 , anthrones claim 56 , and anthrone-like heterocycles.58. The article according to wherein the crosslinking agent is a compound having a formula selected from (a) to (g):{'sup': 1', '2', '3', '4, 'sub': 'm', 'claim-text': wherein L is ...

THREE-DIMENSIONAL STRUCTURE FOR CARDIAC MUSCULAR TISSUE REGENERATION AND MANUFACTURING METHOD THEREFOR

The present invention provides a preparation method of a three-dimensional construct for regenerating a cardiac muscle tissue comprising; a step of forming a three-dimensional construct by printing and crosslinking the first bioprinting composition comprising a tissue engineering construct forming solution containing decellularized extracellular matrix and a crosslinking agent, and cardiac progenitor cells, and the second bioprinting composition comprising the tissue engineering construct forming solution, mesenchymal stem cells and a vascular endothelial growth factor, to arrange the first bioprint layer and the second bioprint layer alternately; and a step of obtaining a crosslink-gelated three-dimensional construct by thermally gelating the crosslinked three-dimensional construct, and a three-dimensional construct for regenerating a cardiac muscle tissue, and the preparation method according to the present invention not only equally positions the cardiac progenitor cells in the construct but also implements a vascular network composed of vascular cells in the construct, so that the viability of cells can be maintained for a long time and the cell transfer efficiency into the myocardium can be significantly improved. 1. A method of preparing a three-dimensional construct for regenerating a cardiac muscle tissue comprising ,(a) forming a three-dimensional construct by printing a first bioprinting composition comprising a tissue engineering construct forming solution containing decellularized extracellular matrix and cardiac progenitor cells, and a second bioprinting composition comprising the tissue engineering construct forming solution, mesenchymal stem cells and a vascular endothelial growth factor, to arrange the first bioprint layer and the second bioprint layer alternately; and(b) carrying out the thermal gelation for the three-dimensional construct,wherein the (a) step is performed at a temperature at which no thermal gelation occurs, and the (b) step is ...

Polymer-based material having covalently bonded enzymatically degradable peptide sequences

A polymer-based material having covalently bonded enzymatically degradable peptide sequences not degradable by the biological and metabolic activity of cells and tissues is disclosed, wherein the peptide sequences are incorporated into the polymer-based material or conjugated to the polymer-based material. The peptide sequence can be part of the three-dimensional or two-dimensional structure of the polymer-based material. A controlled degradation of a covalent bond in the peptide sequence is effected. Use of such polymer-based material for an in vitro production of cell cultures or tissues or organs, for an in vivo stabilization of donated cells, tissues or organs is also disclosed. An adhesive bond between the material and the sample, i.e. cells, tissues, or organs is controlledly degradable without destroying the integrity of the sample.

Decellularized Tissue as a Microcarrier for Cell Culture and Expansion

A microcarrier for cell culture and expansion is provided. The microcarrier includes decellularized mammalian tissue. Further, the microcarrier has an average particle size ranging from about 10 micrometers to about 600 micrometers. A method of forming a decellularized mammalian tissue microcarrier for cell culture and expansion is also provided, along with a method for treating a mammalian tissue defect via a decellularized mammalian tissue microcarrier on which cells from the same tissue type as the decellularized mammalian tissue are expanded. 1. A microcarrier for cell culture and expansion comprising decellularized mammalian tissue , wherein the microcarrier has an average particle size ranging from about 10 micrometers to about 600 micrometers.2. The microcarrier of claim 1 , wherein the decellularized mammalian tissue originates from a human donor claim 1 , a specific human patient claim 1 , or a non-human mammal.3. The microcarrier of claim 1 , wherein the decellularized mammalian tissue originates from embryonic tissue claim 1 , neonatal tissue claim 1 , natal tissue claim 1 , juvenile tissue claim 1 , or adult tissue.4. The microcarrier of claim 1 , wherein the decellularized mammalian tissue originates from articular cartilage tissue claim 1 , bone tissue claim 1 , heart tissue claim 1 , liver tissue claim 1 , skin tissue claim 1 , or gall bladder tissue.5. The microcarrier of claim 1 , wherein the microcarrier is compatible with cells harvested from mammalian tissue of a same type as the decellularized mammalian tissue.6. The microcarrier of claim 1 , wherein the decellularized mammalian tissue is micronized.7. The microcarrier of claim 1 , wherein the decellularized mammalian tissue is digested and functionalized.8. The microcarrier of claim 7 , wherein the decellularized mammalian tissue is cross-linked.9. The microcarrier of claim 1 , wherein the microcarrier has a honeycomb microstructure.10. The microcarrier of claim 1 , wherein the microcarrier ...

FUNCTIONALIZED SUBSTRATE TO MANIPULATE CELL FUNCTION AND DIFFERENTIATION

The invention relates to a scaffold for steering cells into a predetermined direction of cell functionality, preferably a cell differentiation scaffold for steering cells into a predetermined direction of cell differentiation. The scaffold comprises a polydimethylsiloxane (PDMS)-, or rubber-, or silicone-based polymeric surface, and one or more cell functionality-inducing stimuli, preferably one or more cell differentiation-inducing stimuli, coupled to the polymeric surface.

TWO AND THREE DIMENSIONAL DECELLULARIZED ECM CONSTRUCTS AND USES THEREFOR

A microfabricated multi-tissue system for in vitro drug toxicity testing having a plurality of layers, each of which is formed of decellularized tissue extracellular matrix (ECM) including parenchymal cells and non-parenchymal cells attached thereto. Also disclosed is a method for producing a decellularized ECM paste, and methods for producing an ECM construct and a porous 3-D scaffold from the decellularized ECM paste. 1. A microfabricated multi-tissue system for in vitro drug toxicity testing , comprising a plurality of layers , each of which is formed of decellularized tissue extracellular matrix (ECM) and has a thickness of 10 μm to 2 mm , wherein at least a first layer has parenchymal cells attached thereto and at least a second layer has non-parenchymal cells attached thereto , each layer contains only a single cell type , and the first layer is stacked on the second layer such that the non-parenchymal cells extend survival of the parenchymal cells and maintain a differentiated state thereof.2. The microfabricated multi-tissue system of claim 1 , wherein the parenchymal cells are hepatocytes claim 1 , cardiomyocytes claim 1 , kidney epithelial cells claim 1 , enterocytes claim 1 , beta cells claim 1 , or cortical neurons.3. The microfabricated multi-tissue system of claim 1 , wherein the non-parenchymal cells are macrophages claim 1 , fibroblasts claim 1 , epithelial cells claim 1 , adipocytes claim 1 , or endothelial cells.4. The microfabricated multi-tissue system of claim 1 , wherein the plurality of layers are arranged in a tubular structure having a lumen and an exterior surface.5. The microfabricated multi-tissue system of claim 4 , wherein the ECM is decellularized tissue from lung claim 4 , liver claim 4 , heart claim 4 , kidney claim 4 , intestine claim 4 , tendon claim 4 , pancreas claim 4 , brain claim 4 , skin claim 4 , fat claim 4 , cartilage claim 4 , spleen claim 4 , bone claim 4 , or tumor.6. The microfabricated multi-tissue system of claim 5 , ...

PROTEINASE-FREE COATINGS FOR COLONY PASSAGING

A cell culture article includes a substrate having a polymer coating that is conducive to colony passaging of cells cultured on the coating. Example polymer coatings are formed from polygalacturonic acid (PGA), alginate, or combinations thereof. Cells cultured on the polymer coating can be separated from the substrate as a colony or layer of cells by exposing the polymer coating to (i) a chelating agent, (ii) a proteinase-free enzyme, or (iii) a chelating agent and a proteinase-free enzyme. 1. A substrate for culturing cells , comprising:a polymer coating disposed on a surface of the substrate, wherein the polymer coating is cross-linked or grafted to the substrate and comprises at least one of PGA and alginate.2. The substrate according to claim 1 , wherein the polymer coating is cross-linked with calcium ions.3. The substrate according to claim 1 , wherein the polymer coating thickness ranges from 10 nm to 1000 microns.4. The substrate according to claim 1 , wherein the substrate is selected from the group consisting of microcarriers claim 1 , dishes claim 1 , bottles claim 1 , beakers and flasks.5. The substrate according to claim 1 , wherein the degree of cross-linking is uniform across the polymer coating thickness.6. The substrate according to claim 1 , wherein the degree of cross-linking decreases across the polymer coating thickness in the direction of the substrate.7. The substrate according to claim 1 , further comprising a cell adhesion layer on the polymer coating.8. The substrate according to claim 1 , further comprising a cell adhesion layer on the polymer coating selected from the group consisting of ECM proteins and synthetic molecules.9. A method for making an article for culturing cells claim 1 , comprising:forming a polymer coating on a substrate surface, wherein the polymer coating is cross-linked or grafted to the substrate and comprises at least one of PGA and alginate.10. The method according to claim 9 , wherein the degree of cross-linking is ...

SYSTEMS AND METHODS FOR CULTURING CELLS IN SUSPENSION

A method of culturing adherent cells in suspension is provided that includes culturing adherent cells on a first substrate in a first suspension, harvesting the adherent cells from the first substrate, and transfecting the harvested adherent cells using electro-poration. The method also includes, after the step of transfecting, suspending the transfected adherent cells in a second suspension. A dissolution process for dissolving the second microcarrier particle to harvest the cells or cell products is also provided. This dissolution process includes adding a chelator, such as EDTA, to the second suspension for a predetermined time to separate the cells from the second microcarrier; and isolating the cells or cell products from a remainder of the second suspension after the predetermined time. The dissolution process is performed without enzymes such as pectinase or protease. 1. A method of culturing adherent cells in suspension , comprising:culturing adherent cells on a first substrate in a first suspension;harvesting adherent cells from the first substrate;transfecting the harvested adherent cells using electroporation;after the step of transfecting, suspending the transfected adherent cells in a second suspension.2. The method of claim 1 , wherein claim 1 , after electroporation claim 1 , the cells are recovered on a second substrate in suspension or in another suspension format.3. The method of claim 1 , the method further comprising harvesting the cells or products of the cells from the second suspension.4. The method of claim 1 , wherein the first substrate comprises a first microcarrier particle.5. The method of claim 1 , wherein the transfected adherent cells are suspended in the second suspension on a second substrate.6. The method of claim 5 , wherein the second substrate comprises a second microcarrier particle.7. The method of claim 6 , the method further comprising a dissolution process for dissolving the second microcarrier particle to harvest the cells ...

PROTEINASE-FREE COATINGS FOR COLONY PASSAGING

A cell culture article includes a substrate having a polymer coating that is conducive to colony passaging of cells cultured on the coating. Example polymer coatings are formed from polygalacturonic acid (PGA), alginate, or combinations thereof. Cells cultured on the polymer coating can be separated from the substrate as a colony or layer of cells by exposing the polymer coating to (i) a chelating agent, (ii) a proteinase-free enzyme, or (iii) a chelating agent and a proteinase-free enzyme. 18-. (canceled)9. A method for making an article for culturing cells , comprising:forming a polymer coating on a substrate surface, wherein the polymer coating is cross-linked with calcium ions and comprises at least one of polygalacturonic acid (PGA) and alginate; andforming a cell adhesion layer on the polymer coating, the cell adhesion layer comprising at least one of extracellular matrix (ECM) proteins and synthetic molecules.10. The method according to claim 9 , wherein the degree of cross-linking is uniform across the polymer coating thickness.11. (canceled)12. The method according to claim 9 , comprising cross-linking the polymer coating after forming the polymer coating on the substrate.13. (canceled)14. The method according to claim 12 , wherein the degree of cross-linking decreases across the polymer coating thickness in the direction of the substrate.15. A method for culturing cells claim 12 , comprising:forming a polymer coating on a substrate surface, wherein the polymer comprises at least one of PGA and alginate;forming a cell adhesion layer on the polymer coating;culturing cells on the cell adhesion layer; andseparating the cells from the cell adhesion layer as a colony or layer of cells by exposing the polymer coating to (i) a chelating agent, (ii) a proteinase-free enzyme, or (iii) a chelating agent and a proteinase-free enzyme.16. The method according to claim 15 , wherein the chelating agent is EDTA.17. The method according to claim 15 , wherein the proteinase- ...

COACERVATE MICRO AND/OR NANO DROPLETS AND HYDROGELS

A composition includes a plurality of coacervate micro and/or nanodroplets of oxidized alginate and a methacrylated gelatin. 120-. (canceled)21. A method for promoting tissue growth in a subject comprising:administering a coacervate hydrogel to a target site in the subject, the coacervate hydrogel comprising: crosslinked oxidized alginate and methacrylated gelatin that form a hydrogel matrix and a plurality of coacervate microdroplets and/or nanodroplets suspended in the matrix, wherein the oxidized alginate has an oxidation percentage of at least 10% of uronic acid units of alginate and the methacrylated gelatin has a methacrylation percentage of about 10% to about 99% of amine groups of gelatin.22. The method of claim 21 , wherein at least one bioactive agent is incorporated in the coacervate microdroplets and/or nanodroplets and/or matrix.23. The method of claim 21 , wherein the oxidized alginate has an oxidation percentage of up to 50% of uronic acid units of alginate.24. The method of claim 21 , wherein the oxidized alginate is methacrylated and has a methacrylation percentage up to 45% of alginate carboxylic acid reactive groups.25. The method of claim 22 , wherein the hydrogel matrix includes a plurality of cells and the plurality of coacervate microdroplets and/or nanodroplets provide controlled release of the bioactive agent to the plurality of cells.26. The method of claim 25 , wherein the bioactive agent comprises BMP-2 and the cells comprise hMSCs.27. The method of claim 21 , wherein the coacervate hydrogel is administered to a tissue defect.28. The method of claim 27 , wherein the tissue defect is a bone and/or cartilage defect.29. A method for promoting tissue growth in a subject comprising:administering a coacervate hydrogel to a target site in the subject, the coacervate hydrogel comprising: a crosslinked oxidized methacrylated alginate and a methacrylated gelatin that form a hydrogel matrix and a plurality of coacervate microdroplets and/or ...

Chitin Whisker-Enhanced Hyaluronic Acid Cell Scaffold and Preparation Method Thereof

Provided are a chitin whisker-enhanced hyaluronic acid cell scaffold and a preparation method thereof. Components of the cell scaffold include chitin whiskers and cross-linked hyaluronic acid. The chitin whisker-enhanced hyaluronic acid cell scaffold is obtained by dispersing chitin whiskers into deionized water using ultrasound, followed by addition of hyaluronic acid and uniform mixing to obtain an aqueous solution, adjusting a pH value of the aqueous solution to be in a range of 4.0 to 6.0, subjecting the aqueous solution to a cross-linking reaction, dialyzing a reaction product in a phosphate buffer solution, and freeze drying a resulting product. The chitin whisker-enhanced hyaluronic acid cell scaffold and the preparation method thereof can increase a mechanical property and a resistance to degradation of a scaffold material and expand an application scope of hyaluronic acid cell scaffolds.

BLOOD VESSEL MIMIC AND METHOD FOR CULTURING BLOOD VESSEL MIMIC

A method for culturing a blood vessel mimic according to an embodiment of the present invention comprises the steps of: printing a lower structure of a chamber; printing a blood vessel mimic on the lower structure; printing an upper structure of the chamber on the lower structure and the blood vessel mimic; connecting, to both ends of the blood vessel mimic, tubes connected to a circulating pump, respectively; and operating the circulating pump to circulate a fluid through the blood vessel mimic. 1. A method for culturing a blood vessel mimic , which comprises the steps of:printing a blood vessel mimic, such that a solution in which calcium ions are dissolved forms a core layer; a tubular first layer that encompasses the core layer is formed using a first bioink in which vascular endothelial cells and alginate are mixed with a decellularized extracellular matrix isolated from a blood vessel tissue; and a tubular second layer that encompasses the first layer is formed using a second bioink, in which smooth muscle cells and alginate are mixed with a decellularized extracellular matrix isolated from a blood vessel tissue;connecting, to both ends of the blood vessel mimic, tubes connected to a circulating pump, respectively; andoperating the circulating pump to circulate a fluid through the blood vessel mimic through the core layer.2. The method of claim 1 , wherein claim 1 , in the printing a blood vessel mimic claim 1 , the first layer and the second layer are crosslinked by reacting with the calcium ions.3. The method of claim 1 , wherein the method further comprises controlling the perfusion pressure of the fluid by controlling the circulating pump claim 1 , such that the first layer is cultured with vascular endothelial cells and the second layer is cultured with smooth muscle cells claim 1 , andthe vascular endothelial cells are arranged such that the flow direction of the fluid becomes the long axis, and the smooth muscle cells are arranged such that a direction ...

Tumor model for breast cancer cell migration studies and related methods

A method for creating a tumor model includes encapsulating cancer cells in a first solution, disposing the first solution on a spacer, cross-linking the first solution and creating one or more high stiffness constructs, disposing a second solution around the one or more high stiffness constructs, and cross-linking the second solution and creating a low stiffness matrix surrounding the one or more low stiffness constructs.

ADIPOSE TISSUE MATRICES

The present disclosure provides tissue products produced from adipose tissues, as well as methods for producing such tissue products. The tissue products can include acellular extracellular matrices. In addition, the present disclosure provides systems and methods for using such products. 1. A tissue product , comprising:a decellularized adipose extracellular tissue matrix, wherein the tissue matrix has been formed into a sponge, and wherein the tissue matrix is partially cross-linked to maintain a porous structure of the sponge.2. The product of claim 1 , wherein the tissue matrix has been processed to remove at least some lipids.3. The product of claim 1 , wherein the tissue matrix is freeze-dried.4. The product of claim 1 , wherein the tissue matrix maintains the porous structure when implanted in a body.5. The product of claim 1 , wherein the tissue matrix maintains the porous structure when contacted with an aqueous environment.6. The product of claim 1 , wherein the tissue matrix maintains the porous structure when compressed.7. The product of claim 1 , wherein the tissue matrix contains hyaluronic acid and chondroitin sulfate.8. A tissue product claim 1 , comprising:an adipose extracellular tissue matrix comprising particles of decellularized adipose tissue formed into a sponge, and wherein the tissue matrix is partially cross-linked to maintain a porous structure of the sponge.9. The product of claim 8 , wherein the particles of decellularized adipose tissue are produced by cutting claim 8 , grinding claim 8 , or blending adipose tissue.10. The product of claim 8 , wherein the particles of decellularized adipose tissue are freeze-dried.11. The product of claim 8 , wherein the tissue matrix maintains the porous structure when implanted in a body.12. The product of claim 8 , wherein the tissue matrix maintains the porous structure when contacted with an aqueous environment.13. The product of claim 8 , wherein the tissue matrix maintains the porous structure ...

HYDROGEL BIOMIMETIC FOR INVASIVE DISEASES

An extracellular biomimetic for assessing and analyzing cell invasion includes hydrogel matrix and a first peptide crosslinked to the hydrogel matrix, where the first peptide is responsive to a first substance released by diseased cells upon invasion into the biomimetic. The biomimetic further includes at least one modulating agent enabling cell invasion independent from said first substance. The hydrogel matrix can comprise hyaluronate modified with furanyl functional groups, and the modulating agent can be viscoelastic polymer forming reversible crosslinks within the hydrogel matrix. Examples of the viscoelastic polymer include methyl cellulose, or functionalized methyl cellulose, for example, with thiol functional groups. The first substance released by diseased cells is an enzyme, for example, matrix metalloproteinase (MMP). The biomimetic can be used for drug screening to identify compounds that reduce the invasion and viability of the diseased cells, for example, cells from the lung, brain, breast, prostate, and human pluripotent stem cells. 1. An extracellular biomimetic for culturing diseased cells , comprising:hydrogel matrix,a first extracellular matrix protein-mimetic peptide crosslinked to the hydrogel matrix, said first extracellular matrix protein-mimetic peptide being responsive to a first substance released by diseased cells upon invasion into the extracellular biomimetic, andat least one modulating agent enabling cell invasion independent from said first substance.2. The extracellular biomimetic according to claim 1 , wherein the hydrogel matrix comprises hyaluronate or hyaluronic acid claim 1 , modified with furanyl functional groups.3. The extracellular biomimetic according to claim 2 , wherein the furanyl functional groups are furan claim 2 , or furan substituted with alkyl- claim 2 , aryl- claim 2 , or electron-donating functional groups.4. The extracellular biomimetic according to claim 1 , wherein the modulating agent is at least one ...

Polymeric Carriers and Methods

Provided are methods of controlling disassociation of cells from a carrier, compositions, and methods of collecting cells. The methods of controlling disassociation of cells from a carrier may include contacting a polymeric carrier with one or more digesting agents to disassociate at least a portion of a plurality of cells from the polymeric carrier. The polymeric carrier may be crosslinked with a crosslinker including at least one of a redox sensitive moiety, a UV light sensitive moiety, a pH sensitive moiety, and a temperature sensitive moiety. 1. A method of controlling disassociation of cells from a carrier , the method comprising:providing a polymeric carrier and a plurality of cells adhered to the polymeric carrier; andcontacting the polymeric carrier with one or more digesting agents to disassociate at least a portion of the plurality of cells from the polymeric carrier;wherein the polymeric carrier is crosslinked with a crosslinker comprising at least one redox sensitive moiety.2. The method of claim 1 , wherein the at least one redox sensitive moiety comprises a disulfide bond.13. A method of controlling disassociation of cells from a carrier claim 1 , the method comprising:providing a polymeric carrier and a plurality of cells adhered to the polymeric carrier; andcontacting the polymeric carrier with one or more digesting agents to disassociate at least a portion of the plurality of cells from the polymeric carrier;wherein the polymeric carrier is crosslinked with a crosslinker comprising at least one of a UV light sensitive moiety, a pH sensitive moiety, and a temperature sensitive moiety.14. The method of claim 13 , wherein the crosslinker comprises the UV light sensitive moiety claim 13 , and the UV light sensitive moiety is a photoreversibly dimerizable moiety or a photocleavable moiety.19. The method of claim 14 , wherein the crosslinker comprises the photocleavable moiety claim 14 , and the photocleavable moiety comprises an o-nitrobezene based ...

Photodegradable hydrogel, culture device, method for forming tissue, and method for separating cells

Provided are a photodegradable hydrogel in which cells can be embedded in the photodegradable gel without causing cytotoxicity when the cells are embedded in the photodegradable gel by allowing the cells to coexist at the time of preparation of the photodegradable gel, and which contains a protein as one of the main components; a culture device using the same; a method for forming tissue; and a method for separating cells. A photodegradable hydrogel is obtained by condensation of an alkyne group contained in a cyclooctyne ring or an azacyclooctyne ring of the following compound A with an azido group of the following compound B. (Compound A) A compound is a photocleavable crosslinker which contains a main chain having a linear type- or a branched type- (of three or more branches) polyethylene glycol structure, a photodegradable nitrobenzyl group disposed at both terminals or a branched terminal of the main chain, and a group having a cyclooctyne ring or an azacyclooctyne ring disposed at a terminal side of the nitrobenzyl group. (Compound B) A compound is an azide-modified protein in which a main chain is a protein and at least some of an amino group present at lysine and arginine side chains of the main chain and an amino group present at a terminal of the main chain are modified with the azido group.

Three Dimensional Matrix for Cancer Stem Cells

Synthetic inert 3D gel culture systems are described that can be finely tuned to exhibit desired and predetermined physical, chemical, mechanical, and biochemical properties. The culture system can be utilized to study the effect of microenvironmental factors on cancer cell response, and in particular on cancer stem cell (CSC) response. Cancer cells can be encapsulated in a crosslinked gel system having a narrow range of predetermined gel stiffness. One or more biochemical factors including peptides that can affect the growth, development, and/or proliferation of CSCs can be incorporated in the system to examine the effects of the factor(s) on the encapsulated cells with regard to growth, proliferation, size, etc. 1. A three dimensional hydrogel matrix comprising a crosslinked inert synthetic polymer that is absent of ligands that can interact with cell surface receptors , the hydrogel matrix further comprising a peptide conjugated to the matrix , the three dimensional hydrogel matrix having an elastic modulus of from 2 kilopascals to 70 kilopascals.2. The three dimensional hydrogel matrix of claim 1 , wherein the three dimensional hydrogel matrix has an elastic modulus of from about 2.5 kilopascals to about 10 kilopascals.3. The three dimensional hydrogel matrix of claim 1 , the peptide affecting the growth claim 1 , development claim 1 , and/or proliferation of a cancer stem cell.4. The three dimensional hydrogel matrix of claim 1 , wherein the peptide comprises a CD44 binding peptide or a mutant thereof claim 1 , an integrin binding peptide or a mutant thereof claim 1 , or a heparin binding peptide or a mutant thereof.5. The three dimensional hydrogel matrix of claim 1 , wherein the peptide comprises RLVSYNGIIFFLK (SEQ ID NO.: 17) claim 1 , VLFGFLKIYSRIN (SEQ ID NO.: 18) claim 1 , GRGDS (SEQ ID NO.: 19) claim 1 , GRDGS (SEQ ID NO.: 20) claim 1 , WQPPRARI (SEQ ID NO.: 21) claim 1 , or RPQIPWAR (SEQ ID NO.: 22).6. The three dimensional hydrogel matrix of further ...

BIOFUNCTIONALIZED HYDROGEL FOR CELL CULTURE

Provided are biomaterials useful for cell culture, method of preparation thereof, and use thereof. The present biomaterial comprises a crosslinked hydrogel and a peptide chemically attached to the hydrogel, wherein the peptide comprises a histidine-alanine-valine (HAV) sequence. In particular, the present biomaterial may be useful for culturing neurons, brain endothelial cells, and/or glial cells, supporting the formation of synaptically connected neural networks, and growing stem cell-derived organoids that more closely resemble human organs.

POROUS CELLULAR SCAFFOLD COMPRISING SERUM-DERIVED PROTEIN, AND PRODUCTION METHOD THEREFOR

Provide are a porous cell scaffold including a serum-induced protein and a method of manufacturing the same. A porous cell scaffold according to an embodiment may stably and continuously incubate cells, show a culture pattern suitable for the characteristics of each cell to simulate actual tissues, and have a stable culture and high in vivo engraftment rate. Accordingly, the porous cell scaffold can be usefully used in the evaluation of drug activity and toxicity using organoids, for use in cell therapy products, or in the production of a target protein. 1. A porous cell scaffold comprising a serum-induced protein obtained in such a manner that a serum or plasma protein aqueous solution is treated with a cross-linking agent to cross-link proteins therein and then a reducing agent is used to cause a reduction reaction.2. The porous cell scaffold of claim 1 , wherein the serum-induced protein is obtained by homogenizing a reaction product after reduction with the reducing agent.3. The porous cell scaffold of claim 1 , wherein the cross-linking agent comprises one selected from dextran dialdehyde claim 1 , 1-ethyl-3-[3-dimethylaminopropyl]carbodiimide hydrochloride claim 1 , vinylamine claim 1 , 2-aminoethyl methacrylate claim 1 , 3-aminopropyl methacrylamide claim 1 , ethylene diamine claim 1 , ethylenfor exampleycol dimethacrylate claim 1 , methyl methacrylate claim 1 , N claim 1 ,N′-methylene-bisacrylamide claim 1 , N claim 1 ,N′-methylenebis-methacrylamide claim 1 , diallyltartardiamide claim 1 , allyl(meth)acrylate claim 1 , lower alkylenfor exampleycol di(meth)acrylate claim 1 , poly lower alkylenfor exampleycol di(meth)acrylate claim 1 , lower alkylene di(meth)acrylate claim 1 , divinyl ether claim 1 , divinyl sulfone claim 1 , divinylbenzene claim 1 , trivinylbenzene claim 1 , trimethylolpropane tri(meth)acrylate claim 1 , pentaerythritol tetra(meth)acrylate claim 1 , bisphenol A di(meth)acrylate claim 1 , methylenebis(meth)acrylamide claim 1 , triallyl ...

OSTEOPOROSIS MODEL COMPRISING CALCIUM PHOSPHATE HYDROGEL COMPOSITION AND USE THEREOF

Provided is a method of preparing a hydrogel composition including a uniform content of calcium phosphate, wherein a hydrogel composition prepared by the method has a uniform content of calcium phosphate, and thus may be used to quantify phosphates contained in the hydrogel composition. Provided is an in-vitro 3D osteoporosis model including a calcium phosphate hydrogel composition, wherein osteoblasts and osteoclasts may be three-dimensionally co-cultured inside a biogel, such that the osteoporosis model may be fabricated according to an intended use or clinical stage. Further, the model contains a calcium phosphate hydrogel with a uniform content of phosphate and thus enables quantification of calcium phosphate through measurement of phosphates, and therefore, the model may be used to screen candidate compounds for an osteoporosis drug and may effectively predict therapeutic effects of the drug on osteoporosis. 1. A method comprising:preparing a first composition by dissolving chitosan in a gelatin solution; preparing a second composition by dispersing calcium phosphate in a calcium chloride solution; andmixing the first composition with the second composition, to thereby prepare a calcium phosphate hydrogel composition.2. The method of preparing a hydrogel composition of claim 1 , further comprising: preparing a hydrogel bead composition by adding dropwise the hydrogel composition into an alkaline solution.3. The method of preparing a hydrogel composition of claim 1 , wherein the chitosan is included in an amount of 0.1 wt % to 10 wt % in the first composition.4. The method of preparing a hydrogel of claim 1 , wherein the calcium phosphate is included in an amount of 0.1 wt % to 10 wt % in the second composition.5. The method of preparing a hydrogel of claim 1 , wherein the preparation of the second composition further comprises conducting sonification subsequent to dispersal of the calcium phosphate in the calcium chloride solution.6. The method of preparing a ...

CELL CULTURE SCAFFOLD MATERIAL, RESIN FILM, CELL CULTURE VESSEL, AND METHOD FOR CULTURING A CELL

To provide a cell culture scaffold material capable of enhancing adhesiveness of cells. The cell culture scaffold material according to the present invention contains a peptide-conjugated acrylic resin, in which the peptide-conjugated acrylic resin has a first structural part having no peptide portion in a side chain and a second structural part having a peptide portion in a side chain, and solubility parameter calculated by Okitsu's equation for the first structural part is 9.7 (cal/cm)or more and 10.7 (cal/cm)or less. 1. A cell culture scaffold material comprising a peptide-conjugated acrylic resin , whereinthe peptide-conjugated acrylic resin has a first structural part having no peptide portion in a side chain and a second structural part having a peptide portion in a side chain, and{'sup': 3', '1/2', '3', '1/2, "solubility parameter calculated by Okitsu's equation for the first structural part is 9.7 (cal/cm)or more and 10.7 (cal/cm)or less."}2. The cell culture scaffold material according to claim 1 , wherein the first structural part has a poly(meth)acrylic acid ester skeleton.3. The cell culture scaffold material according to claim 1 , wherein the number of amino acid residues in the peptide portion in the second structural part is 10 or less.4. A resin film formed of the cell culture scaffold material according to .5. The resin film according to claim 4 , wherein compressive elastic modulus at a frequency of 1 Hz measured in ion exchange water after immersing the resin film in the ion exchange water at 37° C. for 24 hours in accordance with ISO14577-1 using a nanoindenter device is 1 GPa or more.6. The resin film according to claim 4 , which has a water swelling ratio of 70% or less.7. The resin film according to claim 4 , which has a sea-island structure claim 4 , wherein an island portion in the sea-island structure contains the peptide portion.8. A cell culture vessel equipped with the resin film according to in at least a part of cell culture area.9. A ...

CULTURED CELL LEAFLET MATERIAL

A prosthetic heart valve provided herein can include a cultured cell tissue leaflet. In some cases, a prosthetic heart valve can include a plurality of leaflets secured together and retained within the expandable tubular member. The cultured cell tissue can be obtained by culturing fibroblast cells, smooth muscle cells, or a combination thereof to form a sheet of cultured cells and chemically cross-linking the fibroblast cells while under tension. In some cases, the cultured cell tissue can be radially tensioned. In some cases, the cultured cell tissue can be bi-axially tensioned. 1. A prosthetic heart valve comprising a plurality of leaflets secured together and retained within the expandable tubular member , each leaflet comprising radially or biaxially oriented and chemically cross-linked cultured cell tissue material.2. The prosthetic heart valve of claim 1 , wherein the cultured cell material is cultured from fibroblast cells.3. The prosthetic heart valve of claim 2 , wherein the fibroblast cells are dermal fibroblast cells.4. The prosthetic heart valve of claim 3 , wherein the dermal fibroblast cells are bovine dermal fibroblast cells.5. The prosthetic heart valve of claim 1 , wherein the cultured cell material is cultured from cells including smooth muscle cells.6. The prosthetic heart valve of claim 5 , wherein the smooth muscle cells are bovine smooth muscle cells.7. The prosthetic heart valve of claim 1 , wherein the cultured cell material is cultured from a mixture of fibroblasts and smooth muscle cells.8. The prosthetic heart valve of claim 7 , wherein the fibroblast cells and fibroblast cells are in a ratio of between 20:80 and 80:20.9. The prosthetic heart valve of claim 1 , wherein the cultured cell tissue is cross-linked with glutaraldehyde.10. The prosthetic heart valve of claim 1 , wherein the cultured cells are cultured for at least 3 weeks.11. The prosthetic heart valve of claim 10 , wherein the cultured cells are cultured for at least 5 weeks.12 ...

EXTRACELLULAR MATRIX-SYNTHETIC SKIN SCAFFOLD

The present invention provides a process or preparing an extracellular matrix composition which comprises: (a) mixing an aqueous solution of fibrinogen with a coagulating agent and a bulking agent and a foaming agent; (b) causing the mixture to foam and coagulate; (c) incubating the mixture obtained in step (b) with a cross-linking agent; and (d) washing the cross-linked composition obtained in step (c) to remove the cross-linking agent. Wherein the foaming agent consists of or comprises one or more surfactant agent(s) from the class of sugar-surfactants. The invention also relates to the formulation mixture as such, and to the products of the process. 1. A process for preparing an extracellular matrix composition which comprises:(a) mixing an aqueous solution of fibrinogen with a coagulating agent and a bulking agent and a foaming agent;(b) causing the mixture to foam and coagulate;(c) incubating the mixture obtained in step (b) with a cross-linking agent; and(d) washing the cross-linked composition obtained in step (c) to remove the cross-linking agentwherein the foaming agent consists of or comprises one or more surfactant agent(s) from the class of sugar-surfactants.2. A process according to wherein the fibrinogen is present at a purity level of greater than one of 75% claim 1 , 80% claim 1 , 85% claim 1 , 90% claim 1 , 95% claim 1 , 97% or 99%.3. A process according to wherein the aqueous solution of fibrinogen is essentially free of other protein.4. A process according to wherein fibrinogen is present as truncated forms of fibrinogen claim 1 , such as fibrin A claim 1 , fibrin B claim 1 , fibrin C claim 1 , fibrin D claim 1 , fibrin X and fibrin Y.5. A process according to wherein the truncated form of fibrinogen is fibrin E.6. A process according to wherein fibrinogen is present as an aqueous solution buffered to a pH of between 4 and 10 claim 1 , wherein preferably the buffer is MES/NaCl or HEPES buffered saline.7. A process according to wherein the mixture ...

Porous Polymer Scaffold Useful for Tissue Engineering in Stem Cell Transplantation

The present invention relates to the synthesis of porous polymer scaffold from polyethyleneglycol-polyurethane having castor oil linkages under controlled conditions and their use as stem cell delivery vehicles thereby accelerating the tissue regeneration process. The present invention further studies the biodegradability, stability and biocompatibility of porous polymer scaffolds in varios cell lines and primary bone marrow stem cells. Particularly the present invention further relates to the physio-chemical characterization of the porous polymer scaffolds. 1. A porous polymer scaffold for tissue engineering in stem cell transplantation consisting of a crosslinker , polyether backbone , an isocyanate containing compound , and a secondary component.2. The porous polymer scaffold of claim 1 , wherein the crosslinker is a triglyceride selected from the group consisting of castor oil claim 1 , palm oil claim 1 , soybean oil claim 1 , cotton seed oil claim 1 , and linseed oil.3. The porous polymer scaffold of claim 2 , wherein the crosslinker is a triglyceride of castor oil.4. The porous polymer scaffold of claim 1 , wherein the polyether backbone is selected from the group consisting of di-hydroxyl claim 1 , di-amine claim 1 , and di-carboxyl terminated compounds.5. The porous polymer scaffold of claim 1 , wherein the polyether backbone is selected from the group consisting of polyethylene glycol (PEG) claim 1 , polypropylene glycol (PPG) claim 1 , polytetramethylene glycol (PTMG) claim 1 , block copolymers thereof claim 1 , branched/graft copolymers thereof claim 1 , and combinations thereof.6. The porous polymer scaffold of claim 5 , wherein the polyether backbone is polyethylene glycol (PEG) with molecular weight of 400-10000 Daltons.7. The porous polymer scaffold of claim 1 , wherein the isocyanate containing compound is selected from the group consisting of methylene diphenylene diisocyanate (MDI) claim 1 , polymeric methylene diphenylene diisocyanate (p-MDI) ...

CARRIER FOR CELL CULTURING AND A METHOD OF PREPARATION THEREOF

A carrier for cell culturing that contains a multiwell plate, where at least one of the wells of the multiwell plate has a porous substrate having the porosity of ≥90% and adapted for cell culturing, and the porous substrate adheres to the surface of the well. A method for preparation of the carrier for cell culturing is also provided. 1. A carrier for cell culturing , which contains a multiwell plate , wherein at least one of the wells of the said multiwell plate contains a porous substrate , preferably having the porosity of ≥90% and adapted for cell culturing , and wherein the said porous substrate adheres to the surface of the said well.2. The carrier according to claim 1 , wherein the porous substrate is provided in at least 25% of the wells claim 1 , more preferably in at least 50% of the wells or in all the wells of the multiwell plate.3. The carrier according to claim 1 , wherein the multiwell plate is made of a material selected from the group consisting of plastics claim 1 , glass claim 1 , ceramics claim 1 , metals claim 1 , and combinations of these materials.4. The carrier according to claim 1 , wherein the porous substrate is composed of at least two layers which differ mutually in at least one of: material composition claim 1 , presence or absence of additives claim 1 , composition of additives claim 1 , porosity claim 1 , pore size claim 1 , pore connectivity.5. The carrier according to claim 1 , wherein the pore size of the porous substrate is within the range from 0.1 to 1000 μm claim 1 , preferably between 5 and 1000 μm or between 100 and 2000 nm or within the range from 50 to 600 μm.6. The carrier according to claim 1 , wherein the material of the porous substrate is selected from the group consisting of proteins of the extracellular matrix (ECM); structural proteins such as collagens claim 1 , fibrin claim 1 , silk fibroin claim 1 , elastin or gelatine; polysaccharides such as hyaluronic acid and its derivatives claim 1 , chitosan and its ...

ENGINEERED SUBSTRATES FOR HIGH-THROUGHPUT GENERATION OF 3D MODELS OF TUMOR DORMANCY, RELAPSE AND MICROMETASTASES FOR PHENOTYPE SPECIFIC DRUG DISCOVERY AND DEVELOPMENT

Methods to form a novel aminoglycoside based hydrogel for high-throughput generation of 3D dormant, relapsed and micrometastatic tumor microenvironments are disclosed. In addition, methods of screening agents against tumor cells grown in the 3D environments disclosed herein that include, for example, screening of lead drugs and therapies for an effect on dormant, relapsed and/or micrometastatic tumor cells. 2. The hydrogel of claim 1 , wherein a mole ratio between said aminoglycoside and said polymeric compound is from about 1:1.5 to 1:3.3. The hydrogel of claim 1 , wherein said aminoglycoside is (2S)-4-amino-N-[(1R claim 1 ,2S claim 1 ,3S claim 1 ,4R claim 1 ,5 S)-5-amino-2-[(2S claim 1 ,3R claim 1 ,4S claim 1 ,5S claim 1 ,6R)-4-amino-3 claim 1 ,5-dihydroxy-6-(hydroxymethyl)oxan-2-yl]oxy-4-[(2R claim 1 ,3R claim 1 ,4S claim 1 ,5S claim 1 ,6R)-6-(aminomethyl)-3 claim 1 ,4 claim 1 ,5-trihydroxyoxan-2-yl]oxy-3-hydroxycyclohexyl]-2-hydroxybutanamide claim 1 , and/or salt or hydrate thereof.7. The hydrogel of claim 2 , further comprising a mechanical stiffness of about 7 kilopascals (KPa) to about 100 KPa.8. The hydrogel of claim 2 , further comprising a non-adhesive surface.9. A method to generate a 3D tumor microenvironment (3DTM) using the cross-linked hydrogel of claim 1 , comprising overlaying a first plurality of cancer cells and culturing said cancer cells under conditions and for a duration sufficient to form a spheroidal 3DTM.10. The method of claim 9 , wherein the plurality of cancer cells comprises a seeding density of 1 claim 9 ,000 to 50 claim 9 ,000 cells.11. The method of claim 9 , wherein a size of the spheroidal 3DTM is dependent on the seeding density of the plurality of cancer cells.12. The method of claim 9 , wherein the plurality of cancer cells is selected from the group consisting of T24 bladder cancer cells claim 9 , PC3 prostate cancer cells claim 9 , PC3-eGFP prostate cancer cells claim 9 , and MDA-MB-231 breast cancer cells.13. The method of ...

Visible light polymerization of polyethylene glycol (peg) hydrogels

Provided herein are compositions and methods for generating visible light photopolymerized hydrogels to support cell viability, expansion, and encapsulation. The present disclosure provides a composition, comprising a visible light harvesting complex, a photoinitiator, a co-initiator, a di-thiol-terminated crosslinker, and at least one cysteine-containing peptide. The present disclosure provides a method of generating a visible light photopolymerized hydrogel. In further embodiments that method comprises generating a 3-dimensional endothelial network comprising the visible light photopolymerized hydrogel. In additional embodiments the method comprises generating a hydrogel network comprising the visible light photopolymerized hydrogel comprising at least one cell.

CELLULAR RESPONSE TO SURFACE WITH NANOSCALE HETEROGENEOUS RIGIDITY

An elastomeric substrate comprises a surface with regions of heterogeneous rigidity, wherein the regions are formed by exposing the elastomeric substrate to an energy source to form the regions such that the regions include a rigidity pattern comprising spots. 1. An elastomeric substrate comprising a surface with regions of heterogeneous rigidity , wherein the regions are formed by exposing the elastomeric substrate to an energy source to form the regions such that the regions include a rigidity pattern comprising spots.2. The elastomeric substrate of claim 1 , wherein the regions provide for a differential functional response from cells cultured upon the rigidity pattern of the regions.3. The elastomeric substrate of claim 2 , wherein the differential functional response comprises at least one of: differential focal adhesion of the cells; differential cell differentiation of the cells; differential immune response; or growth of the cells.4. The elastomeric substrate of claim 2 , wherein the cells comprise at least one of stem cells claim 2 , T-cells claim 2 , cancer cells claim 2 , nerve cells claim 2 , osteoblasts claim 2 , and muscle cells.5. The elastomeric substrate of claim 2 , wherein at least some of the spots include a lateral dimension that is greater than or equal to 250 nanometers.6. The elastomeric substrate of claim 2 , wherein at least some of the spots include a lateral dimension that is less than or equal to 250 nanometers.7. The elastomeric substrate of claim 1 , wherein the energy source comprises at least one of a focused electron beam or deep ultraviolet light.8. The elastomeric substrate of claim 1 , wherein the elastomeric substrate comprises poly(dimethylsiloxane) or a poly(dimethylsiloxane)-based polymer.9. The elastomeric substrate of claim 1 , wherein the regions of heterogeneous rigidity are formed at at least one of a microscale or a nanoscale so that the spots comprise micrometer or submicrometer scale spots.10. A method of culturing ...

PHOTOPOLYMER COMPOSITION AND APPLICATION THEREOF

The present disclosure provides a photopolymer composition and the applications thereof. The photopolymer composition comprises: 5 weight percent to 15 weight percent of gelatin methacrylate (GelMA), 0.1 weight percent to 5 weight percent of silanized biologically active additive, 0.1 weight percent to 5 weight percent of photoinitiator, and 75 weight percent to 95 weight percent of a solvent. Compared to a conventional hydrogel, the hydrogel prepared from the photopolymer composition of the present disclosure has improved compressive strength, mechanical strength and stability. Accordingly, the hydrogel is applicable to biomedical research and tissue repair. 1. A photopolymer composition , comprising:5 weight percent to 15 weight percent of gelatin methacrylate (GelMA);0.1 weight percent to 5 weight percent of silanized biologically active additive;75.1 weight percent to 5 weight percent of photoinitiator; and75 weight percent to 95 weight percent of a solvent.2. The photopolymer composition according to claim 1 , wherein the silanized biologically active additive comprises silanized hydroxyapatite claim 1 , silanized β-tricalcium phosphate (β-TCP) or silanized bio-active glass.3. The photopolymer composition according to claim 1 , the photoinitiator comprises 2 claim 1 ,2′-Azobis[2-Methyl-N-(2-hydroxyethyl) propionamide].4. The photopolymer composition according to claim 1 , wherein the photoinitiator can be excited by light with wavelength in a range from 400 nm to 800 nm so as to induce photopolymerization.5. The photopolymer composition according to claim 1 , wherein the solvent comprises water claim 1 , phosphate buffered saline (PBS) claim 1 , conditioned media from cell line or cell culture media.6. A three-dimensional cell culture media claim 1 , comprising the photopolymer composition according to .7. A tissue repair composition claim 1 , comprising the photopolymer composition according to .8. A method for preparing a three-dimensional cell culture media ...

COMPOSITIONS AND METHODS OF MAKING AND USING PROTEIN-FUNCTIONALIZED HYDROGELS

Among the various aspects of the present disclosure is the provision of a hydrogel-based substrate comprising an aldehyde-containing component, such as N-ethanal acrylamide. The hydrogel component allows for functionalization of a hydrogel through conjugation of proteins (e.g., collagen) to the hydrogel in the absence of a post hoc crosslinking component. 1. A substrate comprising a polyacrylamide (PA) hydrogel comprising an aldehyde-containing acrylamide suitable for protein functionalization , wherein protein functionalization of the PA hydrogel enables protein fiber formation of a tunable protein fiber length.3. The substrate of claim 1 , wherein the PA hydrogel further comprises an acrylamide co-polymer and a bis-acrylamide monomer crosslinker.4. The substrate of claim 1 , wherein the PA hydrogel comprises:(i) between about 1% and about 20% acrylamide by volume;(ii) between about 0.05% and about 5% bis-acrylamide by volume; or "the PA hydrogel has a Young's modulus or stiffness between about 0.1 kPa and about 200 kPa.", '(iii) between about 0.5% and about 2% N-ethanal acrylamide by volume, wherein,'}5. The substrate of claim 1 , wherein an extracellular matrix (ECM) protein claim 1 , optionally collagen claim 1 , comprising an N-termini (ϵ-amino groups) region claim 1 , is bound to an aldehyde group of the aldehyde-containing acrylamide.6. The substrate of claim 1 , wherein the substrate does not comprise an intermediate post hoc crosslinker claim 1 , optionally claim 1 , sulfosuccinimidyl 6-[4′-azido-2′-nitro-phenylamino]hexanoate (sulfo-SANPAH) claim 1 , or N-Hydroxysuccinimide (NHS)-ethyl (dimethylaminopropyl) carbodiimide (EDC) for protein functionalization.7. The substrate of claim 1 , wherein(i) the tunable protein fiber length average is between about 0.1 μm and 100 μm; or(ii) the substrate is a stiff substrate if a Young's moduli of the substrate is more than about 2 kPa or the substrate is a soft substrate if a Young's moduli of the substrate is less ...

ENCAPSULATION AND CARDIAC DIFFERENTIATION OF hiPSCs IN 3D PEG-FIBRINOGEN HYDROGELS

The present invention relates to the production of cell cultures and tissues from undifferentiated pluripotent stem cells using three-dimensional biomimetic materials. The resultant cell cultures or tissues can be used in any of a number of protocols including testing chemicals, compounds, and drugs. Further, the methods and compositions of the present invention further provide viable cell sources and novel cell delivery platforms that allow for replacement of diseased tissue and engraftment of new cardiomyocytes from a readily available in vitro source. The present invention includes novel methods required for the successful production of cell cultures and tissues, systems and components used for the same, and methods of using the resultant cell and tissue compositions. 1. A method of producing a three-dimensional cell culture or tissue comprising:combining a population of pluripotent stem cells (PSCs) with a biomimetic material to form a biomimetic-PSC suspension;treating said biomimetic-PSC suspension to produce a three-dimensional biomimetic-PSC microenvironment; andculturing said biomimetic-PSC microenvironment to differentiate the PSCs into at least one type of somatic cell.2. The method of wherein the biomimetic material is a hydrogel.3. The method of wherein the hydrogel is a covalently-linkable hydrogel.4. The method of wherein the covalently-linkable hydrogel is a PEG-based hydrogel.5. The method of wherein the PEG-based hydrogel comprises PEG-fibrinogen.6. The method of wherein said treating said biomimetic-PSC suspension further comprises placing said biomimetic-PSC suspension into a mold.7. The method of wherein said microenvironment is selected from the group consisting of microislands claim 1 , cardiac discs claim 1 , strings claim 1 , macrotissues claim 1 , and microspheres claim 1 , and combinations thereof.8. The method of wherein said treating said biomimetic-PSC suspension to produce a three-dimensional biomimetic-PSC microenvironment comprises ...

Methods and compositions for t cell activation

Among the various aspects of the present disclosure is the provision of methods, synthetic DC, and compositions for T cell activation. The present disclosure provides for synthetic dendritic cells (DCs), methods of generating synthetic dendritic cells (DCs), methods of generating T cell-encapsulated gelatin microspheres and microcapsules, methods of activating T cells using synthetic DCs, methods for expanding T cells against individualized antigen-specific mutational antigens using synthetic DCs, and methods of treating a chronic disease (e.g., HIV, HPV) or cancer using the synthetic DCs.

Thermally Induced Gelation Of Collagen Hydrogel And Method Of Thermally Inducing Gelling A Collagen Hydrogel

The present invention relates to collagen hydrogels. Particularly, the invention relates to hydrogels comprising a telopeptide collagen (“telo-collagen”) and an atelopeptide collagen (“atelo-collagen”); hydrogels comprising collagen and chitosan; methods of making the hydrogels; methods of reducing gelation of a hydrogel mixture at room temperature; methods of reducing compaction of cells; and methods of culturing cells on such hydrogels.

CONSTRUCTS AND METHODS FOR ENGINEERING COMPLEX CELL SYSTEMS

This application provides constructs for use as complex cell systems of a desired shape and methods of preparing thereof. The constructs comprise cells contained within a biocompatible gel matrix deposited on a scaffold material optionally cut into defined patterns and impregnated with a crosslinking agent, wherein the biocompatible gel matrix crosslinks upon contact with the crosslinking agent on the scaffold. By stacking multiple alternating layers of the scaffold material cut into defined patterns and the biocompatible gel matrix deposited on the scaffold in defined patterns, complex 3D structures with features like embedded channels are be formed. These complex cell system constructs can be used as in vitro models of biological processes. 1. A construct comprising:a) at least one first layer comprising a scaffold, the scaffold comprising a crosslinking agent; and 'and wherein the scaffold comprises at least one pattern cut into the scaffold.', 'b) at least one second layer comprising a biocompatible gel, the biocompatible gel comprising a plurality of cells, wherein the biocompatible gel is crosslinked to the crosslinking agent,'}2. The construct of claim 1 , wherein the pattern defines at least one void.3. The construct of claim 1 , wherein the biocompatible gel is present in a pattern on the at least one second layer.4. The construct of claim 1 , wherein the construct is a three-dimensional structure comprised of a plurality of alternating layers of the first layer and the second layer claim 1 , wherein the layers are joined by crosslinking of the biocompatible gel with the crosslinking agent of an adjacent scaffold layer.5. The construct of claim 4 , comprising at least one three-dimensional void claim 4 , wherein the three-dimensional void is defined by at least one pattern cut into at least one scaffold.6. The construct of claim 5 , wherein the three-dimensional void is defined by a plurality of patterns cut into a plurality of scaffolds.7. The construct of ...

BIOMIMETIC NETWORKS COMPRISING POLYISOCYANOPEPTIDE HYDROGELS

A polymer hydrogel having a polymer formed by the crosslinking reaction of a polymeric unit A according to formula (I), 2. The polymer hydrogel according to claim 1 , wherein the amount of polymer in the hydrogel ranges between 0.01 wt. % and 1 wt. % claim 1 , more preferably between 0.02 wt. % and 0.5 wt. % claim 1 , wherein the amount of water in the hydrogel ranges between 90 and 99.99 wt. % relative to the total of the hydrogel.3. The polymer hydrogel according to claim 1 , wherein the concentration of functional groups FG ([FG]) ranges between 20-200 μM.4. The polymer hydrogel according to claim 1 , wherein the molar ratio between FG and functional groups F1 claim 1 , F2 claim 1 , F ranges between 0.5:1 and 2:1.5. The polymer hydrogel according to claim 1 , wherein the number of ethylene glycol units (m) ranges independently between 2 and 10 claim 1 , preferably the number of ethylene glycol units is 3 or 4 claim 1 , most preferably 3.6. The polymer hydrogel according to claim 1 , wherein k ranges between 0.02 and 0.04.7. The polymer hydrogel according to claim 1 , wherein functional groups F1 claim 1 , F2 claim 1 , F and functional groups FG that can give covalently couplings are selected from alkyne-azide coupling claim 1 , dibenzocyclooctyne-azide coupling claim 1 , bicyclo[6.1.0]non-4-yne-based-azide couplings claim 1 , vinylsulphone-thiol coupling claim 1 , maleimide-thiol coupling claim 1 , methyl methacrylate-thiol coupling claim 1 , ether coupling claim 1 , thioether coupling claim 1 , biotin-strepavidin coupling claim 1 , amine-carboxylic acid resulting in amides linkages claim 1 , alcohol-carboxylic acid coupling resulting in esters linkages claim 1 , tetrazine-trans-cyclooctene coupling and NHS-ester (N-hydroxysuccinimide ester)-amine coupling.8. The polymer hydrogel according to claim 7 , wherein the couplings are based on azide-alkene and/or azide-alkyn coupling such as dibenzocyclooctyne-azide coupling claim 7 , bicyclo[6.1.0]non-4-yne—based-azide ...

Method and device for forming a gel particle slurry

A method of forming a gel particle slurry includes providing a first solution that includes a cross-linkable hydrogel polymer macromer and an optional first crosslinker in a first depot and optionally a second solution in a second depot that is separated from the first depot by a mixing unit that includes a mixing element; and reversibly transferring the first solution and the optional second solution through the mixing unit between the first depot and the second depot such that the first solution and the optional second solution are mixed and agitated to form the gel particle slurry.

HYDROGEL PRECURSOR FORMULATION AND THE USE THEREOF

A hydrogel precursor formulation which is in the form of an unreacted powder. The formulation comprises an activating enzyme, preferably thrombin, a cross-linking enzyme, preferably a transglutaminase, and more preferably factor XIII transglutaminase. The cross-linking enzyme is activatable by the activating enzyme in water with or without a buffer, and at least one structural compound A. The structural compound is crosslinkable by a selective reaction mediated by the crosslinking enzyme to form a hydrogel, wherein the cross-linking enzyme is activated. 117-. (canceled)18. A hydrogel precursor formulation in the form of an unreacted powder comprising:an activating enzyme,a cross-linking enzyme, wherein the cross-linking enzyme is activatable by the activating enzyme in water with or without a buffer,at least one structural compound A,wherein said structural compound is crosslinkable by a selective reaction mediated by the crosslinking enzyme to form a hydrogel.19. The hydrogel precursor formulation according to claim 18 , wherein the precursor formulation is substantially deprived of divalent ions.20. The hydrogel precursor formulation according to claim 18 , wherein the at least one structural compound comprises at least two distinct reactive groups.21. The hydrogel precursor formulation according to claim 18 , wherein the at least one structural compound comprises an acyl moiety and an amine moiety.22. The hydrogel precursor formulation according to claim 18 , wherein the hydrogel precursor formulation comprises at least one further hydrogel compound.23. The hydrogel precursor formulation according to claim 18 , wherein the at least one structural compound is a multi-branched polyethylene glycol.24. A process for the production of a hydrogel precursor formulation in the form of an unreacted powder claim 18 , comprising: an activating enzyme,', 'a cross-linking enzyme, wherein the cross-linking enzyme is activatable by the activating enzyme in water, and', 'at ...

Thermally Induced Gelation Of Collagen Hydrogel And Method Of Thermally Inducing Gelling A Collagen Hydrogel

The present invention relates to collagen hydrogels. Particularly, the invention relates to hydrogels comprising a telopeptide collagen (“telo-collagen”) and an atelopeptide collagen (“atelo-collagen”); hydrogels comprising collagen and chitosan; methods of making the hydrogels; methods of reducing gelation of a hydrogel mixture at room temperature; methods of reducing compaction of cells; and methods of culturing cells on such hydrogels.

CELL CULTERING MATERIALS

A material for binding to a cell culturing protein is disclosed. The material contains a bulk-modified elastomer comprising a plurality of fatty acid moieties covalently bound to the elastomer bulk, wherein the carboxylic acid groups of said moieties are available to provide said binding. Also disclosed are a fluidic device module, a cell culturing scaffold, a fluidic device, the method of synthesizing such a material and a drug testing method. With such a material, a (monolithic) fluidic device module may be manufactured in as few as a single step injection molding process. 1. A material for binding to a cell culturing protein , the material comprising a bulk-modified elastomer ,wherein the bulk-modified elastomer comprises a plurality of fatty acid moieties covalently bound to the elastomer bulk,wherein the carboxylic acid groups of the moieties are available to provide the binding.2. The material of claim 1 , wherein each of the fatty acid moieties is covalently bound to the elastomer bulk through a cross-linking reaction between a vinyl or hydride functional group of the elastomer and an unsaturated carbon-carbon bond of an unsaturated fatty acid.3. The material of claim 2 , wherein the unsaturated fatty acid is selected from the group consisting of myristoleic acid claim 2 , palmitoleic acid claim 2 , sapienic acid claim 2 , oleic acid claim 2 , elaidic acid claim 2 , vaccenic acid claim 2 , linoleic acid claim 2 , linoeladic acid claim 2 , α-linolenic acid claim 2 , arachidonic acid claim 2 , eicospaentaenoic acid claim 2 , erucic acid and docosahexaenoic acid.4. The material of any of claim 1 , wherein the elastomer comprises a polybutadiene backbone or a silicone backbone.5. The material of claim 4 , wherein at least a fraction of the carboxylic acid groups within the silicone backbone is saponified.6. A cell culturing scaffold comprising the material of any of and a cell culturing protein bound to at least some of the carboxylic acid groups.7. The cell ...

3D STIMULATED TISSUE CONSTRUCTS AND METHODS OF MAKING THEREOF

This application discloses a method for preparing a construct comprising preparing a mixture of an extracellular matrix and a plurality of cells suspended in a first cell culture medium, applying a crosslinking or gelation agent to the mixture, depositing the mixture into a mold of a defined shape, allowing the extracellular matrix in the mixture to crosslink or gel for a duration of about 1 hour to about 4 hours, applying a second cell culture medium to the mixture containing crosslinked or gelled extracellular matrix, and allowing cell directed self-assembly of the mixture for a duration of about 2 hours to about 10 hours to form a construct, wherein the construct is a three-dimensional structure formed within the mold of the defined shape. Optionally, the method further comprises applying at least one stimuli to the mixture or the construct. Also provided are constructs prepared according to the methods disclosed herein. 1. A method for preparing a construct comprising:a) preparing a mixture of an extracellular matrix and a plurality of cells suspended in a first cell culture medium,b) applying a crosslinking or gelation agent to the mixture,c) depositing the mixture from b) into a mold of a defined shape,d) allowing the extracellular matrix in the mixture in c) to crosslink or gel for a duration of about 1 hour to about 4 hours,e) applying an additional cell culture medium to the mixture containing crosslinked or gelled extracellular matrix from d), andf) allowing cell directed self-assembly of the mixture from e) for a duration of about 2 hours to about 10 hours to form a construct,wherein the construct is a three-dimensional structure formed within the mold of the defined shape.2. The method of claim 1 , further comprising removing the construct from the mold.3. The method of claim 1 , wherein the construct retains the defined shape after removal from the mold.4. The method of claim 1 , wherein the extracellular matrix comprises a hydrogel claim 1 , collagen ...

TRANSGLUTAMINASE MEDIATED HIGH MOLECULAR WEIGHT HYALURONAN HYDROGELS

The invention relates to a process for forming a hyaluronan hydrogel, comprising the steps of 2. A process for forming a hyaluronan hydrogel , comprising the steps ofa. providing an aqueous solution of a first hyaluronan peptide conjugate comprising transglutaminase donor peptides and a second hyaluronan peptide conjugate comprising transglutaminase acceptor peptides,b. adding a thrombin polypeptide to said aqueous solution and allowing equilibration of the resulting mixture;c. subsequently, adding a factor XIII polypeptide.3. The process according to any one of the preceding claims ,wherein the aqueous solution of step a. additionally comprises heparin or heparan sulfate, particularly at a concentration from 0.05% to 0.5% (w/v relative to the gel), andwherein the heparin or heparan sulfate comprises covalently attached transglutaminase donor and/or acceptor peptides, particularly wherein 10% to 20% of carboxylic acid groups present in said heparin or heparan sulfate are covalently modified, more particularly covalently modified to contain a modification described by general formula (II) as laid out above, with L, S and Pep having the meaning indicated above.4. The process according to any one of the preceding claims , wherein the concentration of the sum of said first hyaluronan peptide conjugate and said second hyaluronan peptide conjugate is 0.25% (w/v) to 5% (w/v) , particularly 0.75% to 0.95% or from 0.5% to 3% , 0.5% to 2% , or 0.5% to 1.5%.5. A process for modification of a hyaluronan polymer , wherein said hyaluronan polymer is composed of n dimers of D-glucuronic acid moieties and D-N-acetylglucosamine moieties , and wherein said D-glucuronic acid moieties bear reactive carboxylic acid moieties , and said process comprises the steps of:a. thiolation of 5% to 20%, particularly 8-12%, more particularly approximately 10% of said reactive carboxylic acid moieties to yield partially thiolated hyaluronan;b. reacting said partially thiolated hyaluronan with ...

THREE DIMENSIONAL MATRIX FOR CANCER STEM CELLS

Synthetic inert 3D gel culture systems are described that can be finely tuned to exhibit desired and predetermined physical, chemical, mechanical, and biochemical properties. The culture system can be utilized to study the effect of microenvironmental factors on cancer cell response, and in particular on cancer stem cell (CSC) response. Cancer cells can be encapsulated in a crosslinked gel system having a narrow range of predetermined gel stiffness. One or more biochemical factors including peptides that can affect the growth, development, and/or proliferation of CSCs can be incorporated in the system to examine the effects of the factor(s) on the encapsulated cells with regard to growth, proliferation, size, etc. 1. A method of forming a three dimensional hydrogel matrix for supporting a cancer cell , the method comprising:combining an inert synthetic polymer with a crosslinking agent to form a precursor solution;crosslinking the inert synthetic polymer via the crosslinking agent to form the three dimensional hydrogel matrix, wherein the concentration of the crosslinking agent and/or the concentration of the inert synthetic polymer is predetermined in the precursor solution such that the three dimensional hydrogel matrix has a predetermined elastic modulus; andconjugating a peptide to the matrix, the peptide affecting the growth, development, and/or proliferation of a cancer stem cell.2. The method of claim 1 , wherein the inert synthetic polymer comprises polyethylene glycol claim 1 , polyhydroxyethyl methacrylate claim 1 , polyvinylolypyrrolidone claim 1 , or polyvinyl alcohol.3. The method of claim 1 , wherein the inert synthetic polymer is combined with and reacted with the crosslinking agent prior to crosslinking the polymer.4. The method of claim 1 , further comprising encapsulating a population of cells in the three dimensional hydrogel matrix claim 1 , the population of cells comprising cancer stem cells.5. The method of claim 4 , the population of cells ...

PHOTODEGRADABLE CROSS-LINKING AGENT, PHOTODEGRADABLE GEL, CELL CULTURE INSTRUMENT, CELL ARRANGEMENT-SORTING APPARATUS, CELL ARRANGEMENT METHOD, CELL SORTING METHOD, TISSUE FORMING METHOD, AND TISSUE

The present invention provides a photodegradable cross-linking agent capable of manufacturing a photodegradable gel, which has appropriate moisture content and water solubility as a cell carrier and has strength that makes it possible to construct a complicated three-dimensional microstructure. The photodegradable cross-linking agent of the present invention includes a main chain which is composed of branched polyethylene glycol having three or more branched chains and a photodegradable benzyl group which is disposed on the terminus of the branched chains, in which the benzyl group has an active ester group , which is reactive with an amino group or a hydroxyl group, and one or more nitro groups in a benzene ring. 1. A photodegradable cross-linking agent comprising:a polyethylene glycol main chain which has three or more branched chains; anda photodegradable benzyl group which is disposed on the terminus of the polyethylene glycol main chain having the branched chains,the benzyl group having an active ester group, which is reactive with an amino group or a hydroxyl group, and one or more nitro groups in a benzene ring of the benzyl group.2. The photodegradable cross-linking agent according to claim 1 ,wherein the active ester group is a derivative of N-hydroxysuccinimide.3. The photodegradable cross-linking agent according to claim 1 ,wherein the average repetition number of ethylene glycol in the branched chains is within a range of 20 to 500.4. The photodegradable cross-linking agent according to claim 1 ,wherein the number of the branched chains is 4 or 8.5. The photodegradable cross-linking agent according to claim 1 ,wherein the polyethylene glycol main chain has a neopentyl skeleton.6. A photodegradable gel characterized in that it is obtained by reacting the photodegradable cross-linking agent according to with a polymer compound having a total of two or more amino groups or hydroxyl groups in a molecule claim 1 ,the amino groups or the hydroxyl groups in the ...

DRYING FORMULATON FOR HYDROGEL MICROCARRIERS

A method of making a cell culture article is provided. The method includes forming a microcarrier from a microcarrier composition comprising a polygalacturonic acid compound or an alginic acid compound, infiltrating the microcarrier with a drying formulation to form an infiltrated microcarrier, and drying the infiltrated microcarrier to form a dried microcarrier, wherein the drying formulation comprises at least one of a saccharide and a monovalent cation. 1. A method of making a cell culture article , the method comprising:forming a microcarrier from a microcarrier composition comprising a polygalacturonic acid compound or an alginic acid compound;infiltrating the microcarrier with a drying formulation to form an infiltrated microcarrier; anddrying the infiltrated microcarrier to form a dried microcarrier, wherein the drying formulation comprises at least one of a saccharide and a monovalent cation.2. The method according to claim 1 , further comprising sterilizing the dried microcarrier to form a sterilized dried microcarrier.3. The method according to claim 2 , wherein sterilizing the dried microcarrier comprises exposing the dried microcarrier to gamma radiation.4. The method according to claim 1 , further comprising rehydrating the microcarrier.5. The method according to claim 1 , wherein infiltrating the microcarrier with a drying formulation comprises soaking the microcarrier in a solution of the drying formulation.6. The method claim 1 , wherein infiltrating the microcarrier with a drying formulation comprises simultaneously spraying the microcarrier composition and the drying formulation.7. The method according to claim 1 , wherein the drying formulation comprises 1 to 50 wt. % saccharide.8. The method according to claim 1 , wherein the drying formulation comprises 10 to 500 mM monovalent cation.9. The method according to claim 1 , wherein the drying formulation comprises 1 to 50 wt. % saccharide and 10 to 500 mM monovalent cation.10. The method according ...

TISSUE SCAFFOLD

There is provided a tissue scaffold and a method for making a tissue scaffold. The tissue scaffold comprises elastin and optionally fibrin and/or collagen. The elastin in the scaffold may be cross-linked. The elastin that is cross-linked preferably comprises solubilised elastin and is unfractionated. 1. A method for forming a tissue scaffold , comprising cross-linking a composition , the composition comprising elastin , wherein the elastin is unfractionated and comprises solubilised elastin.2. A method according to claim 1 , comprising a step of solubilising elastin.3. A method for forming a tissue scaffold claim 1 , comprising cross-linking a composition comprising unfractionated solubilised elastin.4. A method according to claim 3 , comprising a step of solubilising elastin to form the composition comprising unfractionated solubilised elastin.5. A method according to any preceding claim claim 3 , wherein the elastin is claim 3 , or has been claim 3 , solubilised by contacting with oxalic acid.6. A method according to any preceding claim claim 3 , wherein the elastin is claim 3 , or has been claim 3 , solubilised at a temperature less than 100° C.7. A method according to claim 6 , wherein the step of solubilising the elastin is claim 6 , or has been claim 6 , carried out at a temperature less than or equal to 50° C.8. A method according to claim 7 , wherein the step of solubilising the elastin is claim 7 , or has been claim 7 , carried out at a temperature of 15 to 30° C.9. A method according to any preceding claim claim 7 , wherein the composition that is cross-linked comprises insoluble elastin.10. A method for forming a tissue scaffold claim 7 , comprising cross-linking a composition claim 7 , the composition comprising soluble elastin and insoluble elastin.11. A method according to any preceding claim claim 7 , wherein the composition that is cross-linked comprises collagen and/or fibrin.12. A method according to or claim 7 , or any claim dependent on or claim ...

ENGINEERED SUBSTRATES FOR HIGH-THROUGHPUT GENERATION OF 3D MODELS OF TUMOR DORMANCY, RELAPSE AND MICROMETASTASES FOR PHENOTYPE SPECIFIC DRUG DISCOVERY AND DEVELOPMENT

Methods to form a novel aminoglycoside based hydrogel for high-throughput generation of 3D dormant, relapsed and micrometastatic tumor microenvironments are disclosed. In addition, methods of screening agents against tumor cells grown in the 3D environments disclosed herein that include, for example, screening of lead drugs and therapies for an effect on dormant, relapsed and/or micrometastatic tumor cells. 2. The hydrogel of claim 1 , wherein a mole ratio between said aminoglycoside and said polymeric compound is from about 1:1.5 to 1:3.3. The hydrogel of claim 1 , wherein said aminoglycoside is (2S)-4-amino-N-[(1R claim 1 ,2S claim 1 ,3S claim 1 ,4R claim 1 ,5S)-5-amino-2-[(2S claim 1 ,3R claim 1 ,4S claim 1 ,5S claim 1 ,6R)-4-amino-3 claim 1 ,5-dihydroxy-6-(hydroxymethyl)oxan-2-yl]oxy-4-[(2R claim 1 ,3R claim 1 ,4S claim 1 ,5S claim 1 ,6R)-6-(aminomethyl)-3 claim 1 ,4 claim 1 ,5-trihydroxyoxan-2-yl]oxy-3-hydroxycyclohexyl]-2-hydroxybutanamide claim 1 , and/or salt or hydrate thereof.7. The hydrogel of claim 2 , further comprising a mechanical stiffness of about 7 kilopascals (KPa) to about 100 KPa.8. The hydrogel of claim 2 , further comprising a non-adhesive surface.9. A method to generate a 3D tumor microenvironment (3DTM) using the cross-linked hydrogel of claim 1 , comprising overlaying a first plurality of cancer cells and culturing said cancer cells under conditions and for a duration sufficient to form a spheroidal 3DTM.10. The method of claim 9 , wherein the plurality of cancer cells comprises a seeding density of 1 claim 9 ,000 to 50 claim 9 ,000 cells.11. The method of claim 9 , wherein a size of the spheroidal 3DTM is dependent on the seeding density of the plurality of cancer cells.12. The method of claim 9 , wherein the plurality of cancer cells is selected from the group consisting of T24 bladder cancer cells claim 9 , PC3 prostate cancer cells claim 9 , PC3-eGFP prostate cancer cells claim 9 , and MDA-MB-231 breast cancer cells.13. The method of ...

DRYING FORMULATION FOR HYDROGEL MICROCARRIERS

A method of making a cell culture article is provided. The method includes forming a microcarrier from a microcarrier composition comprising a polygalacturonic acid compound or an alginic acid compound, infiltrating the microcarrier with a drying formulation to form an infiltrated microcarrier, and drying the infiltrated microcarrier to form a dried microcarrier, wherein the drying formulation comprises at least one of a saccharide and a monovalent cation. 113-. (canceled)14. A cell culture article comprising:a polygalacturonic acid compound or an alginic acid compound; anda drying formulation comprising at least one of a saccharide and a monovalent cation,wherein the cell culture article is free of water.15. The cell culture article according to claim 14 , wherein the drying formulation comprises 1 to 50 wt. % saccharide.16. The cell culture article according to claim 14 , wherein the drying formulation comprises 0.5 to 20 wt. % monovalent cation.17. The cell culture article according to claim 14 , wherein the drying formulation comprises 1 to 50 wt. % saccharide and 0.5 to 20 wt. % monovalent cation.18. The cell culture article according to claim 14 , wherein the drying formulation comprises a non-volatile liquid material.19. The cell culture article according to claim 18 , wherein the non-volatile liquid material is selected from the group consisting of DMSO and a low molecular weight polyethylene glycol.20. The cell culture article according to claim 14 , wherein the polygalacturonic acid compound or the alginic acid compound is cross-linked with calcium.21. The cell culture article of claim 14 , wherein the cell culture article comprises a microcarrier comprising the polygalacturonic acid compound or the alginic acid compound claim 14 , wherein the drying formulation is infiltrated into the microcarrier.22. The cell culture article of claim 14 , wherein the drying formulation comprises 10 to 500 mM monovalent cation.23. The cell culture article of claim 14 , ...

Crosslinked Peptide Hydrogels

The present invention relates to hydrogels comprising a plurality of amphiphilic peptides and/or peptoids capable of self-assembling into three-dimensional macromolecular nanofibrous networks, which entrap water and form said hydrogels, wherein at least a portion of said plurality of amphiphilic peptides and/or peptoids is chemically cross-linked. The present invention further relates to methods for preparing such hydrogels and to various uses of such hydrogels, e.g. as cell culture substrates, for drug and gene delivery, as wound dressing, as an implant, as an injectable agent that gels in situ, in pharmaceutical or cosmetic compositions, in regenerative medicine, in tissue engineering and tissue regeneration, or in electronic devices. It also relates to a method of tissue regeneration or tissue replacement using a hydrogel in accordance with the present invention. 149.-. (canceled)50. A hydrogel prepared by a method comprising steps of: {'br': None, 'sub': p', 'n', 'm', 'thiol', 'q, 'Z—(X)—(Y)-AA-Z′,'}, 'dissolving amphiphilic peptides and/or peptoids having the general formulawhereinZ is an N-terminal protecting group,X is, at each occurrence, independently selected from an aliphatic amino acid,Y is, at each occurrence, independently selected from a hydrophilic amino acid,{'sub': 'thiol', 'AAis an amino acid comprising a thiol group, wherein the amino acid comprising a thiol group is preferably selected from cysteine and homocysteine,'}Z′ is a C-terminal protecting group,n is an integer selected from 2 to 6, preferably 2 to 5,m is selected from 0, 1 and 2, preferably 0 and 1,and p and q are independently selected from 0 and 1, wherein, preferably, p is 1,in an aqueous solution,wherein the aqueous solution comprises an oxidizing agent orwherein the method further comprises the step of exposing the ready-made hydrogel to a solution of an oxidizing agent.51. (canceled)52. (canceled)53. A cell culture substrate claim 50 , preferably a cell culture substrate for 3-D ...

BIOPAPERS AS A SUBSTRATE FOR TISSUE CULTURE

A biocompatible membranes made by electrospinning a polymer, having living cells on both surfaces of the membrane, and/or is free of a non-biodegradable structural component. The membranes may be attached to a frame and span a hole in the frame. A method of: providing a biocompatible membrane made by electrospinning a polymer and depositing living cells both surfaces of the membrane and/or attaching the membrane to a frame and spanning a hole in the frame. Different types of cells are deposited on each surface of the membrane. 1. An article comprising:a biocompatible membrane made by electrospinning a polymer; and 'wherein the membrane is attached to the rigid component and spans the hole.', 'a rigid component having a hole;'}2. The article of claim 1 , wherein the membrane comprises a biodegradable material.3. The article of claim 2 , wherein the membrane is free of a non-biodegradable structural component.4. The article of claim 2 , wherein the membrane comprises a structural component comprising a second biodegradable material that degrades slower that the biodegradable material.5. The article of claim 1 , wherein the membrane comprises non-biodegradable fibers.6. The article of claim 1 , wherein the membrane comprises a non-biodegradable structural component.7. The article of claim 1 , wherein the membrane comprises gelatin.8. The article of claim 7 , wherein the gelatin is crosslinked.9. The article of ;wherein rigid components has a plurality of holes; andwherein the membrane spans each of the plurality of holes.10. The article of claim 9 , wherein the portion of the rigid component between the plurality of holes is the same material as the portion of the rigid component surrounding the plurality of holes.11. The article of claim 9 , wherein the portion of the rigid component between the plurality of holes comprises a biodegradable material.12. The article of claim 1 , wherein the article further comprises:living cells one or both surfaces of the membrane.13. ...

GRAPHENE OXIDE-BASED POROUS 3D MESH

A method of making a porous three-dimensional graphene mesh includes combining a graphene-containing material and a polymer having a plurality of hydroxyl groups in an alcohol solvent to form a mixture, adding a salt to the mixture, heating the mixture to form a gel, and washing the gel with water to remove the salt from the gel, leaving behind stable pores to form a scaffold. A three-dimensional porous graphene mesh includes a graphene-containing material and a polymer. The polymer is crosslinked with the graphene-containing material such that the Young's Modulus of the mesh is at least about 5 GPa. 1. A stable three-dimensional material matrix comprising:a graphene-containing material;a polymer, wherein the polymer is crosslinked with the graphene-containing material; andsalt crystals integrated with the graphene-containing material and polymer.210. The three-dimensional material matrix of claim , wherein the crosslinked graphene-containing material and polymer form a scaffold around the salt crystals.3. A three-dimensional porous graphene mesh comprising:a graphene-containing material; anda polymer, wherein the polymer is crosslinked with the graphene-containing material such that the Young's Modulus of the mesh is at least about 5 GPa.412. The three-dimensional graphene mesh of claim , wherein the mesh has a porosity between about 50% and about 90%.512. The three-dimensional graphene mesh of claim , wherein an average pore size of the mesh is between about 5 μm and about 50 μm. This application is a divisional of U.S. application Ser. No. 16/774,921 filed Jan. 28, 2020 for “GRAPHENE OXIDE-BASED POROUS 3D MESH” by Y. Zhang, J. Zhao, and D. Darland, which in turn claims the benefit of and is a continuation of U.S. application Ser. No. 15/917,045 filed Mar. 9, 2018 for “GRAPHENE OXIDE-BASED POROUS 3D MESH” by Y. Zhang, J. Zhao, and D. Darland, now U.S. Pat. No. 10,808,220, which in turn claims the benefit of U.S. Provisional Application No. 62/469,367 filed Mar. 9, ...

CELL CULTURE

The disclosure relates to the fabrication of a three dimensional [3-D] cell culture membrane comprising one or more functionalized surfaces adapted to provide cell culture conditions suitable for the analysis of proliferation, differentiation or function of cells, typically eukaryotic or prokaryotic cells. 1. A three dimensional cell culture substrate comprising: a perforated membrane comprising a cured polymer adapted for cell culture characterized in that said membrane has at least two modified cell culture surfaces wherein the first surface comprises at least one cell culture agent and the second surface comprises a second different cell culture agent , wherein said membrane enhances the proliferation and/or differentiation or function of cells associated with said membrane.2. The substrate according to wherein said membrane comprises a plurality of perforations wherein said perforations are at least 5-1000 μm in diameter.3. The substrate according to claim 2 , wherein the perforations have an aspect ratio not greater than 2.4. The substrate according to claim 1 , wherein said curable polymer is UV curable.5. The substrate according to wherein said UV curable polymer is an acrylate based polymer.6. The substrate according to claim 1 , wherein said cell culture agent and/or said membrane is further modified by inclusion of a cross-linking agent that facilitates the cross-linking of the cell culture agent to said membrane to provide a modified cell culture surface.7. The substrate according to claim 1 , wherein said membrane has a refractive index of between about 1.30 to about 1.50.8. The substrate according to claim 1 , wherein said cell substrate comprises a network of interconnected cell culture microwells.9. The substrate according to wherein the network comprises a plurality of elongate cell culture microwells adapted to provide at least said first and second modified cell culture surfaces.1011.-. (canceled)12. A process for the micro-fabrication of a cell ...

ENCAPSULATION AND CARDIAC DIFFERENTIATION OF hiPSCs IN 3D PEG-FIBRINOGEN HYDROGELS

The present invention relates to the production of cell cultures and tissues from undifferentiated pluripotent stem cells using three-dimensional biomimetic materials. The resultant cell cultures or tissues can be used in any of a number of protocols including testing chemicals, compounds, and drugs. Further, the methods and compositions of the present invention further provide viable cell sources and novel cell delivery platforms that allow for replacement of diseased tissue and engraftment of new cardiomyocytes from a readily available in vitro source. The present invention includes novel methods required for the successful production of cell cultures and tissues, systems and components used for the same, and methods of using the resultant cell and tissue compositions. 120-. (canceled)21. A method of producing a three-dimensional cardiac tissue comprising:combining a population of pluripotent stem cells (PSCs) with a hydrogel precursor solution to form a PSC suspension, the hydrogel precursor solution comprising an acrylate component and a natural hydrogel-forming component chosen from a naturally occurring protein, a naturally occurring polysaccharide, a naturally occurring protein derivative, or a naturally occurring polysaccharide derivative;treating the PSC suspension by cross-linking to produce a three-dimensional PSC microenvironment; andculturing the three-dimensional PSC microenvironment to differentiate the PSCs into a cardiac tissue.22. The method of claim 21 , wherein treating the PSC suspension further comprises placing the PSC suspension into a mold prior to cross-linking.23. The method of claim 21 , wherein the three-dimensional PSC microenvironment is selected from the group consisting of microislands claim 21 , cardiac discs claim 21 , strings claim 21 , macrotissues claim 21 , and microspheres claim 21 , and combinations thereof.24. The method of claim 21 , wherein treating the PSC suspension to produce a three-dimensional PSC microenvironment ...

THREE DIMENSIONAL SOY PROTEIN-CONTAINING SCAFFOLDS AND METHODS FOR THEIR USE AND PRODUCTION

Porous soy protein-based scaffolds and methods for making the scaffolds using 3D printing techniques are provided. Also provided are tissue growth scaffolds comprising the porous soy protein-based scaffolds and methods for growing tissue on the tissue growth scaffolds. The porous soy protein-containing scaffold comprises a plurality of layers configured in a vertical stack, each layer comprising a plurality of strands comprising denatured soy proteins. 1. A method of forming a porous biopolymer-containing scaffold , the method comprising:extruding a slurry comprising a biopolymer in the form of a first layer, the first layer comprising a plurality of strands; andextruding the slurry in the form of one or more additional layers, each additional layer being vertically stacked upon the previously extruded layer and comprising a plurality of strands,wherein the mass flow rate of the slurry is maintained at a substantially constant rate during extrusion by adjusting one or both of the extrusion pressure and extrusion speed during extrusion.2. The method of claim 1 , wherein the extrusion is accomplished via extrusion-based rapid prototyping.3. The method of claim 1 , wherein the biopolymer is denatured soy protein.4. The method of claim 3 , wherein the amount of the denatured soy protein in the slurry is in the range of from about 15 wt % to about 20 wt % and further wherein claim 3 , the slurry further comprises a plasticizer.5. The method of claim 4 , wherein the amount of the plasticizer in the slurry is about 4 wt %.6. The method of claim 3 , wherein the mass flow rate is about 0.0072 g/s.7. The method of claim 1 , wherein the extrusion is carried out at a temperature in the range of from about room temperature to about 40° C.8. The method of claim 1 , wherein the slurry further comprises a growth factor or a drug.9. The method of claim 1 , further comprising solidifying the extruded porous biopolymer-containing scaffold via a post-extrusion treatment.10. The method ...

AZLACTONE BASED THERMALLY CROSSLINKABLE POLYMER COATING FOR CONTROLLING CELL BEHAVIOR

Random copolymers, crosslinked thin films of the random copolymers and cell culture substrates comprising the crosslinked thin films are provided. Also provided are methods of making and using the copolymers, thin films and substrates. The copolymers are polymerized from glycidyl methacrylate monomers and vinyl azlactone monomers. The crosslinked thin films are substrate independent, in that they need not be covalently bound to a substrate to form a stable film on the substrate surface. 2. The cell culture substrate of claim 1 , wherein the copolymer comprises from about 1 to about 15 mole percent of the monomers that provide covalent crosslinks between the backbone chains and from about 99 to about 85 mole percent of the polymerized monomers comprising covalently linked peptide chains.4. The cell culture substrate of claim 1 , wherein the film has a thickness no greater than about 30 nm.5. The cell culture substrate of claim 1 , wherein the substrate is a polymeric substrate.6. The cell culture substrate of claim 4 , wherein the film is not covalently bound to the substrate.7. A method of culturing stem cells using the cell culture substrate of claim 1 , the method comprising seeding the stem cells onto the cell culture substrate and culturing the seeded stem cells in a cell culture medium under cell culturing conditions.9. The coated substrate of claim 8 , wherein the random copolymer comprises from about 1 to about 15 mole percent of the polymerized monomers that provide covalent crosslinks between the backbone chains claim 8 , from about 15 to about 60 mole percent of the polymerized 4 claim 8 ,4-dimethyl-2-vinylazlactone monomer claim 8 , from about 30 to about 85 mole percent of the polymerized polyethylene glycol methyl ether methacrylate monomer claim 8 , and no greater than about 30 mole percent of additional monomer.11. The cell culture substrate of claim 10 , wherein the random copolymer comprises from about 1 to about 15 mole percent of the polymerized ...

BLOOD BRAIN BARRIER MODEL AND METHODS OF MAKING AND USING THE SAME

Provided herein is an in vitro model of the blood brain barrier. In some embodiments, the model includes: an endothelial cell layer, and brain tissue layer comprising neuronal cells, and optionally one or more of astrocytes, pericytes, oligodendrocytes, and microglia. In some embodiments, the model further comprises a porous membrane between said endothelial cell layer and the neuronal cell layer. A microfluidic device comprising the same and methods of use thereof are also provided. 1. An in vitro model of a blood brain barrier , said model comprising:(a) an endothelial cell layer comprising astrocytes, pericytes and endothelial cells (optionally comprising a self-assembled organoid comprising said cells), and optionally smooth muscle cells; and(b) a neuronal cell layer comprising neuronal cells, and optionally oligodendrocytes and/or microglia,optionally wherein said in vitro model further comprises a porous membrane between said endothelial cell layer and said neuronal cell layer.2. The in vitro model of claim 1 , wherein the neuronal cells comprise primary neuronal cells or neuronal progenitor cells claim 1 , and optionally wherein said neuronal cell layer is electrically active.3. The in vitro model of claim 1 , wherein the endothelial cells comprise primary endothelial cells or endothelial progenitor cells.4. The in vitro model of claim 1 , wherein the astrocytes comprise primary astrocytes or astrocyte progenitor cells.5. The in vitro model of claim 1 , wherein the pericytes comprise primary pericytes or pericyte progenitor cells.6. The in vitro model of claim 1 , wherein the neuronal cells claim 1 , endothelial cells claim 1 , astrocytes and/or pericytes are human.7. The in vitro model of claim 1 , wherein the ratio of astrocytes claim 1 , pericytes and endothelial cells of the endothelial cell layer is about 3:1:1 by number of cells claim 1 , respectively.8. The in vitro model of claim 1 , wherein said porous membrane is present and comprises a polymeric ...

METHODS TO GENERATE POLYMER SCAFFOLDS HAVING A GRADIENT OF CROSSLINKING DENSITY

The present invention is directed to a method of making a live cell construct or a support, comprising: (a) providing a non-cellular organic polymer support having a top surface, a bottom surface, and an intermediate portion there between, and (b) contacting a cross-linking agent to one surface of said support for a time sufficient to generate a gradient of cross-linking of said polymer in said intermediate portion. Also provided are live cell constructs, supports, and methods of use of the supports and live cell constructs. 1. A method of making a live cell construct or a support , comprising:(a) providing a non-cellular organic polymer support having a top surface, a bottom surface, and an intermediate portion there between,(b) contacting a cross-linking agent to one surface of said support (e.g., under aqueous conditions) for a time sufficient to generate a gradient of cross-linking of said polymer in said intermediate portion;(c) optionally, Wherein said gradient of cross-linking in said intermediate portion produces a corresponding gradient of free amino and/or carboxy groups in said intermediate portion, coupling a compound of interest to said free amino and/or carboxy groups to produce a gradient of said compound of interest in said intermediate portion;(d) optionally contacting live undifferentiated epithelial cells to said non-cellular support, and(e) optionally propagating an undifferentiated and/or differentiated epithelial cell monolayer on said top surface.2. The method of claim 1 , wherein the cells in the monolayer comprise:(i) undifferentiated cells (e.g., stem or progenitor cells); and(ii) optionally, differentiated cells in combination with the undifferentiated cells.3. (canceled)4. The method of claim 1 , wherein the live undifferentiated epithelial cells are gastrointestinal epithelial cells claim 1 , urinary epithelial cells claim 1 , respiratory epithelial cells claim 1 , reproductive epithelial cells claim 1 , endocrine and endocrine gland ...

Systems and methods for immobilizing extracellular matrix material on organ on chip, multilayer microfluidics microdevices, and three-dimensional cell culture systems

The presently disclosed subject matter provides an approach to address the needs for microscale control in shaping the spatial geometry and microarchitecture of 3D collagen hydrogels. For example, the disclosed subject matter provides for compositions, methods, and systems employing N-sulfosuccinimidyl-6-(4′-azido-2′-nitro-phenylamino)hexanoate (“sulfo-SANPAH”), to prevent detachment of the hydrogel from the anchoring substrate due to cell-mediated contraction.

OPTICALLY TRANSPARENT SILK HYDROGELS

The present application relates to silk fibroin-based hydrogels, methods for making and using the same. 1. A silk fibroin-based hydrogel , having at least 60% transmittance in a visible spectrum.2. The silk fibroin-based hydrogel of claim 1 , having at least 70% transmittance in the visible spectrum.3. The silk fibroin-based hydrogel of claim 1 , having at least 75% transmittance in the visible spectrum.4. The silk fibroin-based hydrogel of claim 1 , having at least 80% transmittance in the visible spectrum.5. The silk fibroin-based hydrogel of claim 1 , having at least 85% transmittance in the visible spectrum.6. The silk fibroin-based hydrogel of claim 1 , having at least 90% transmittance in the visible spectrum.7. The silk fibroin-based hydrogel of claim 1 , having at least 95% transmittance in the visible spectrum.8. The silk fibroin-based hydrogel of any one of - claim 1 , comprising a plurality of crystalized silk fibroin spheres.9. The silk fibroin-based hydrogel of claim 8 , wherein the crystalized silk fibroin spheres have an average diameter ranging between about 10 nm and about 150 nm.10. The silk fibroin-based hydrogel of any one of - claim 8 , having a compressive modulus ranging between about 2 and about 20 kPa when measured with a crosshead speed of about 2.0 mm/hr.11. The silk fibroin-based hydrogel of any one of - claim 8 , wherein the silk fibroin is crosslinked.12. The silk fibroin-based hydrogel of claim 11 , wherein the silk fibroin is crosslinked with a crosslinking agent.13. The silk fibroin-based hydrogel of claim 12 , wherein the crosslinking agent is an amine-to-amine crosslinker claim 12 , amine-to-sulfhydryl crosslinker claim 12 , carboxyl-to-amine crosslinker claim 12 , photoreactive crosslinker claim 12 , sulfhydryl-to-carbohydrate crosslinker claim 12 , sulfhydryl-to-hydroxyl crosslinker claim 12 , sulfhydryl-to-sulfhydryl crosslinker claim 12 , or any combination thereof.14. The silk fibroin-based hydrogel of claim 12 , wherein the ...

Algae Beads

Algae-containing beads comprising a microorganism such as unicellular microalgae, an insoluble carbon source such as char, water, and a crosslinked organic matrix. The beads can further contain clay, such as kaolin. 1. An algal bead comprising unicellular microalgae , char , and a crosslinked organic matrix.2. The bead of claim 1 , further comprising a clay.3. The bead of claim 1 , wherein the organic matrix before crosslinking comprises a plurality of hydroxyl groups that react with a divalent cation to crosslink the matrix.4. The bead of claim 3 , wherein the organic matrix comprises a water soluble polysaccharide selected from the group consisting of alginate salts claim 3 , galactomannan claim 3 , gellan gum claim 3 , carrageenan claim 3 , agarose claim 3 , and mixtures thereof.5. The bead of claim 2 , wherein the clay comprises kaolin.6. The bead of claim 1 , wherein the char comprises a biochar.7. The bead of claim 6 , wherein the biochar is produced from algal biomass or rice hulls.8. The bead of claim 1 , further comprising soluble salts of cations selected from Na+ claim 1 , K+ claim 1 , Mg+2 claim 1 , Ca+2 claim 1 , Fe+3 claim 1 , Mn+2 claim 1 , Zn+2 claim 1 , Cu+2 claim 1 , and Co+2.9. The bead of claim 8 , comprising soluble salts of one or more anions selected from nitrates claim 8 , phosphates claim 8 , hydrogen phosphates claim 8 , dihydrogen phosphates claim 8 , sulfates claim 8 , chlorides claim 8 , EDTA claim 8 , carbonates claim 8 , bicarbonates claim 8 , and molybdates.10Chlorella, Spirulina, Dunaliella, Haematococcus, Crypthecodinium, Schizochytrium, Scenedesmus, Aphanizomenon, Arthrospira, Odontella, Isochrysis, Nannochloropsis, Tetraselmis, Phaeodactylum, Porphyridium,. The bead of claim 1 , wherein the microalgae are selected from the group consisting of and combinations thereof.11. The bead of claim 3 , wherein the divalent ion is selected from Be+2 claim 3 , Mg+2 claim 3 , Ca+2 claim 3 , Sr+2 claim 3 , and Ba+2.12. A method of making a bead ...

POLYMER GEL FOR MEDIUM, MEDIUM, AND METHOD AND KIT FOR CULTURING CELLS

Provided are: a polymer gel for a medium, and a medium in which the stiffness of the polymer gel can be easily and reversibly changed and the shape of cells can be controlled according to the stiffness of the gel; and a method for culturing cells using the medium. The polymer gel for a medium contains a solvent and a crosslinked structure that is crosslinked by reversible bonds. The stiffness of the polymer gel for a medium can be easily and reversibly changed. Accordingly, when the polymer gel for a medium according to the present invention is used, cell morphology and function can be reversibly controlled according to the stiffness of the gel. 2. (canceled)3. (canceled)4. (canceled)5. A medium comprising the cell culture substrate according to .6. A cell culture method comprising culturing cells in a medium claim 1 , the medium comprising a cell culture substrate comprising a polymer gel for a medium claim 1 , the polymer gel comprising a solvent and a crosslinked structure that is crosslinked by reversible bonds claim 1 , the method further comprising adding to the medium a competitive substance having a property of inhibiting formation of the reversible bonds claim 1 , so as to repeatedly perform an operation of increasing or decreasing the concentration of the competitive substance added to the medium.7. (canceled)8. (canceled)9. The cell culture method according to claim 6 , wherein the concentration of the competitive substance contained in the medium is adjusted to 10 mol/L or less.10. A kit comprising the medium according to .11. The cell culture method according to claim 6 , wherein the reversible bonds are at least one member selected from the group consisting of bonds between host groups and guest groups claim 6 , hydrophobic interactions claim 6 , hydrogen bonds claim 6 , ionic bonds claim 6 , coordinate bonds claim 6 , Π-electron interactions claim 6 , and intermolecular interactions other than these.12. The cell culture method according to claim 11 , ...

Rosin-based small molecular weight hydrogelator and its application

The present disclosure discloses a rosin-based small molecular weight hydrogelator and an application thereof, and belongs to the fields of supramolecular chemistry, surfactant science and chemical utilization of rosin. The rosin-based small molecular hydrogel of the present disclosure can gel water at a very low concentration, and the critical gelling concentration is only 0.176 wt %. On average, each gelling agent molecule can hold 13,889 water molecules, which exhibits extremely high gel efficiency and the formed small molecular hydrogel also exhibits extremely high stability. This small molecule hydrogel is derived from the natural product rosin and has a mild nature. It can be used in the fields of drug sustained-release, tissue engineering, daily chemicals, medicine and so on. At the same time, the rosin-based small molecular hydrogel 6-dehydroabietylamide amine oxide in the present disclosure can form a stable gel emulsion for most oils, and can be used in many fields such as food, medicine, daily chemicals, tissue engineering, environmental protection, and water pollution control. 3. A supramolecular hydrogel comprising the compound according to claim 1 , wherein the compound is a gelling factor for forming the supramolecular hydrogel.4. The supramolecular hydrogel according to claim 3 , wherein a concentration of the compound in the supramolecular hydrogel ranges from 3 mmol·Lto 1 claim 3 ,000 mmol·L.5. A sustained-release material comprising the compound according to claim 1 , and a sustained-release substance.6. A pharmaceutical wound dressing comprising a hydrogel claim 1 , wherein the hydrogel comprises the compound according to and an inflammatory or anti-bacterial ingredient claim 1 , wherein the compound is a gelling factor for forming the hydrogel.7. A water-soil moisturizing agent comprising the compound according to .8. A hydrogel mask comprising a hydrogel claim 1 , wherein the hydrogel comprises the compound according to claim 1 , wherein the ...

METHODS OF DIFFERENTIATING STEM CELLS INTO CHONDROCYTES

Disclosed herein are methods of producing chondrocytes from pluripotent stem cells. The invention further provides methods of regenerating cartilaginous tissue. 1. A method of producing a population of chondrogenic precursors , comprising culturing a plurality of mesenchymal stem cell (MSC)-like cells in three-dimensional culture , to generate a population of chondrogenic precursors , a) culturing a population of mechanically-dissected pluripotent cell aggregates (PCA) in a tissue culture-treated vessel until confluency in order to produce PCA-derived cells; and', 'b) passaging the PCA-derived cells at least two times, to generate MSC-like cells., 'wherein the MSC-like cells are produced by a process comprising2. The method of claim 1 , wherein the pluripotent cell aggregates are:a) less than 20% positive for CD73;b) positive for expression of Oct3/4; andc) lacking immunoreactivity to vimentin.3. The method of claim 1 , wherein culturing the plurality of MSC-like cells in three-dimensional culture comprises culturing in three-dimensional aggregate.4. The method of claim 1 , wherein the plurality of mesenchymal stem cell (MSC)-like cells are cultured in the presence of TGFβ3.5. The method of claim 1 , wherein the PCA-derived cells are passaged at least five times.6. (canceled)7. (canceled)8. (canceled)9. The method of claim 1 , wherein the induced pluripotent cell aggregates are derived from fibroblasts.10. The method of claim 1 , wherein the pluripotent cell aggregates are embryonic stem cells.11. The method of claim 1 , wherein the population of chondrogenic precursors express one or more markers selected from: aggrecan claim 1 , annexin A6 claim 1 , Capthesin B claim 1 , CD44 claim 1 , CD151 claim 1 , Collagen II claim 1 , collagen type 2A1 claim 1 , Collagen IV claim 1 , CRTAC1 claim 1 , DSPG3 claim 1 , FoxC1 claim 1 , FoxC2 claim 1 , Sialoprotein II claim 1 , ITM2A claim 1 , Matrilin-1 claim 1 , Matrilin-3 claim 1 , Matrilin-4 claim 1 , MIA claim 1 , Otoraplin ...

Bio-Ink For 3D Printing

The technology relates to a 3D printed hydrogel formed from a maleimide containing polymer cross-linked using a bis-thiol containing cross-linking agent having at least two thiol functional groups, processes for preparing the 3D printed hydrogel, and uses thereof. 1. A 3D printed hydrogel formed from a maleimide containing polymer cross-linked using a bis-thiol containing cross-linking agent having at least two thiol functional groups.2. The 3D printed hydrogel according to claim 1 , wherein the maleimide containing polymer is selected from the group consisting of maleimide containing polysaccharides claim 1 , including polymers containing fructose claim 1 , sucrose or glucose monomers; synthetic polymers claim 1 , including poly(ethylene glycol) (PEG) maleimide claim 1 , poly(hydroxyethyl methacrylate (PHEMA) maleimide claim 1 , poly(E-caprolactone) (PCL) maleimide claim 1 , poly(vinyl alcohol) (PVA) maleimide claim 1 , poly(vinylpyrrolidone) (PVP) maleimide claim 1 , poly(N-isopropylacrylamide) (NIPAAM) maleimide claim 1 , poly(propylene fumarate) (PPF) maleimide claim 1 , poly(ethyleneimine) (PEI) maleimide claim 1 , poly(3-methacrylamidopropyl) trimethylammonium (PMAETMA) maleimide claim 1 , poly(-lysine) (PLL) maleimide) claim 1 , poly(acrylic acid) (PAA) maleimide claim 1 , poly(styrene sulfonate) (PSS) maleimide) claim 1 , poly(acrylic acid-stat-dimethylaminoethyl methacrylamide) (P(AA-stat-DMAEMA)) maleimide claim 1 , and poly(arginine methacrylate) maleimide claim 1 , or derivatives thereof; maleimide containing biopolymers claim 1 , including gelatin maleimide claim 1 , cellulose maleimide claim 1 , hyaluronic acid maleimide and alginate maleimide; maleimide containing nucleobase polymers including maleimide containing polymers of adenine claim 1 , thymine claim 1 , guanine and/or cytosine repeating units; and any combination thereof.3. The 3D printed hydrogel according to claim 2 , wherein the maleimide containing polymer comprises a PEG maleimide.4. The ...

DEVICES AND METHODS FOR SINGLE CELL ANALYSIS

The present disclosure provides systems, methods, and devices for the simultaneous determination of a single cell's response to a stimuli and characterization of its cell response. The present disclosure further provides methods for detection of disease state, clinical management of a subject suffering from a disease, drug screening, prediction of drug response, and stands to help direct drug and diagnostic development for the treatment of disease. 1. A method for detecting a response of a live cell comprising:(a) contacting a live cell to a cell capture array device, wherein said cell capture array device comprises a cell microenvironment and an inducible agent;(b) capturing said live cell in said cell microenvironment;(c) inducing the release of said inducible agent into said cell microenvironment; and(d) detecting a response of said live cell.2. The method of claim 1 , wherein said cell microenvironment further comprises a cell capture moiety.3. The method of claim 1 , wherein said cell microenvironment comprises a hydrogel.4. The method of claim 3 , wherein said live cell is suspended in said hydrogel.5. The method of claim 3 , wherein said hydrogel is crosslinked.6. The method of claim 3 , wherein said hydrogel further comprises nutrients suitable to maintain cell viability.7. The method of claim 1 , wherein said cell microenvironment is suitable for maintaining viability of said live cell.8. The method of claim 1 , wherein said cell microenvironment is of a size suitable to accommodate an individual live cell.9. The method of claim 1 , wherein said cell microenvironment is of a size suitable to bind a target cell based on the size of said target cell.10. The method of claim 1 , wherein said cell microenvironment is at least 10 μm in diameter.11. The method of wherein said cell microenvironment is less than 100 μm in diameter.12. The method of claim 2 , wherein said cell capture moiety is selected from the group consisting of: a peptide claim 2 , a protein ...

METHOD FOR CULTIVATING CELLS IN ADHESION CULTURE BY USING A CELL CULTURE CARRIER IN CAPSULE FORM, AND CELL CULTURE CARRIER THEREFOR

The invention relates to a method for cultivating cells in adhesion culture, comprising at least the following steps: a) dissolving or suspending a cross-linkable, biocompatible material having adhesion points for cells in a cell culture medium; b) suspending cells in the cell culture medium, which contains the cross-linkable, biocompatible material, or in a medium that contains at least one component that is required for the cross-linking of the cross-linkable, biocompatible material; c) introducing the cell suspension into a medium in drops under conditions that initiate or permit the cross-linking of the biocompatible material, wherein either the cell suspension or the medium into which the cell suspension is introduced in drops contains the cross-linkable biocompatible material; d) forming stable, preferably porous capsules from cross-linked biocompatible material, which capsules contain incorporated adherent cells; e) proliferating the adherent cells in the capsules for a specified time period; f) breaking up the capsule material by means of a physical or chemical stimulus and releasing the cells as a cell suspension. In an especially preferred embodiment of the invention, the method is performed cyclically, in that the cells released in step f) are suspended anew in a cell culture medium that contains a cross-linkable, biocompatible material or in a medium that contains at least one component that is required for the cross-linking of the cross-linkable, biocompatible material and steps c)-f) are repeated at least once. 1. A method for cultivating cells in adhesion culture , comprising at least the following steps:a) dissolving or suspending a cross-linkable, biocompatible material with adhesion sites for cells in a cell culture medium,b) suspending cells in the cell culture medium which contains the cross-linkable, biocompatible material, or in a medium which contains at least one component which is required to cross-link the cross-linkable, biocompatible ...

CELL CULTURES AND USE THEREOF

The present disclosure provides an alginate-based 3D cell culture as an in vitro system for enriching and maintaining the stemness properties of a cancer cell line and a reliable in vitro system for the development and evaluation of CSC-targeting agents. 1. A method of treating cells to provide cells enriched with at least one stem-like characteristic comprising embedding cells in a cell culture, wherein the cell culture comprises at least one alginate and at least one crosslinker, and wherein the cells are enriched with at least one stem-like characteristic. The present application claims the benefit of priority under 35 U.S.C. § 119 of U.S. Provisional Patent Application No. 62/308,772 filed Mar. 15, 2016; the content of which is incorporated herein in its entirety by reference.According to recent statistics, about 14 million people are newly diagnosed as having cancer and about 8 million people die of cancer annually in the world. Anti-tumor agents, surgical operations, radiotherapy, immunotherapy, and the like are widely used to treat cancer. Of these, anti-tumor agents are used most often. Anti-tumor agents usually act on the metabolism of cancer cells. However, such metabolic processes occur in not only cancer cells, but also normal cells. As a result, many anti-tumor agents cause unintended side effects.Recent studies have discovered the presence of cancer stem cells. Cancer stem cells (CSCs) are a sub-population of cancer cells (found within tumors or hematological cancers) that possess characteristics normally associated with stem cells. These cells are tumorigenic (tumor-forming), in contrast to the bulk of cancer cells, which are non-tumorigenic. In human acute myeloid leukemia the frequency of these cells is less than 1 in 10,000. There is mounting evidence that such cells exist in almost all tumor types. However, as cancer cell lines are selected from a sub-population of cancer cells that are specifically adapted to growth in tissue culture, the ...

GRAPHENE OXIDE-BASED POROUS 3D MESH

A method of making a porous three-dimensional graphene mesh includes combining a graphene-containing material and a polymer having a plurality of hydroxyl groups in an alcohol solvent to form a mixture, adding a salt to the mixture, heating the mixture to form a gel, and washing the gel with water to remove the salt from the gel, leaving behind stable pores to form a scaffold. A three-dimensional porous graphene mesh includes a graphene-containing material and a polymer. The polymer is crosslinked with the graphene-containing material such that the Young's Modulus of the mesh is at least about 5 GPa. 1. A method of making a porous three-dimensional graphene mesh , the method comprising:combining a graphene-containing material and a polymer having a plurality of hydroxyl groups in an alcohol solvent to form a mixture;adding a salt to the mixture;heating the mixture to form a gel; andwashing the gel with water to remove the salt from the gel leaving behind stable pores to form a scaffold.2. The method of claim 1 , wherein the graphene-containing material comprises graphene oxide (GO).3. The method of claim 2 , wherein the graphene-containing material comprises a dispersion of graphene oxide (GO) in ethanol.4. The method of claim 1 , wherein the mixture is heated to a temperature between about 60° C. and about 85° C. for between about 1 hour and about 36 hours to form the gel.5. The method of claim 1 , further comprising:drying the gel at a temperature between about 40° C. and about 70° C. for between about 1 hour and about 24 hours.6. The method of claim 1 , wherein the graphene-containing material and the polymer are combined at a graphene:polymer weight ratio between 1:1 and 1:3.12.7. The method of claim 1 , wherein the scaffold has a porosity between about 50% and about 90%.8. The method of claim 1 , wherein an average pore size of the scaffold is between about 5 μm and about 50 μm.9. The method of claim 1 , wherein the alcohol solvent is methanol claim 1 , ethanol ...

THREE DIMENSIONAL HYDROGELS FOR CULTURING ORGANOIDS

The invention provides hydrogels and methods for three-dimensional (3D) culture of adult epithelial stem cells and uses thereof. 1. A method for obtaining an epithelial cell organoid , comprising culturing stem cells in a biofunctional 3D hydrogel , wherein:a) the cells comprise isolated tissue or organoid fragments and wherein the cells are cultured in conditions suitable for organoid formation; orb) the cells comprise single or clusters of stem cells, and wherein the cells are first cultured in conditions suitable for cell expansion and subsequently cultured in conditions suitable for organoid formation,wherein the hydrogel comprises a crosslinked hydrophilic polymer and a bioactive molecule, wherein the bioactive molecule is laminin-111 or a functional variant thereof, and wherein the hydrogel has a shear modulus between 0.05-0.5 kPa, preferably between 0.05-0.3 kPa, more preferably 0.08-0.3 kPa, or most preferably 0.2-0.3 kPa or most preferably 0.08-0.15 kPa.2. The method of wherein the hydrogel does not comprise an RGD-containing ligand in addition to laminin-111 or a functional variant thereof.3. A method for obtaining an epithelial cell organoid claim 1 , comprising culturing stem cells in a biofunctional 3D hydrogel claim 1 , wherein:a) the cells comprise isolated tissue or organoid fragments and wherein the cells are cultured in conditions suitable for organoid formation; orb) the cells comprise single or clusters of stem cells, and wherein the cells are first cultured in conditions suitable for cell expansion and subsequently cultured in conditions suitable for organoid formation,wherein the hydrogel comprises a crosslinked hydrophilic polymer and a bioactive molecule, and wherein the hydrogel has a shear modulus between 0.05-3.1 kPa.43. The method of claim b) wherein the shear modulus of the hydrogel decreases over time.5. The method of claim 4 , wherein the shear modulus of the hydrogel at the start of the method is 0.5 to 2.5 kPa claim 4 , preferably 1 ...

CELL CULTURE DEVICE AND CELL CULTURE METHOD

A cell culture device includes a hydrogel layer formed into a pattern on a substrate and a layer of cell culture part formed on the substrate to cover the hydrogel layer. The surface of the cell culture part functions as the plane for seeding a first cell species. The hydrogel layer is impregnated with a cell growth factor, and has a thickness which enables release of the cell growth factor from the hydrogel layer into the cell culture part throughout the cell culture period. 1. A cell culture device comprising ,a substrate,a hydrogel layer being formed into a pattern on the substrate, a layer of cell culture part being formed on the substrate to cover the hydrogel layer;a surface of the cell culture part functions as the plane for seeding a first cell species,the hydrogel layer is impregnated with a cell growth factor, andthe cell growth factor is gradually released from the hydrogel layer into the cell culture part.2. A cell culture device according to claim 1 , wherein the hydrogel layer has a thickness which enables continuous release of the cell growth factor from the hydrogel layer into the cell culture part for a period ranging from 2 days to 21 days.3. A cell culture device according to claim 1 , wherein the hydrogel layer is composed of a thermally cross-linked gelatin.4. A cell culture device according to claim 2 , wherein the hydrogel layer is composed of a thermally cross-linked gelatin.5. A cell culture device according to claim 1 , wherein the water content of a hydrogel constituting the hydrogel layer ranges from 70% to 99%.6. A cell culture device according to claim 2 , wherein the water content of a hydrogel constituting the hydrogel layer ranges from 70% to 99%.7. A cell culture device according to claim 4 , wherein the water content of a hydrogel constituting the hydrogel layer ranges from 70% to 99%.8. A cell culture device according to claim 1 , wherein the hydrogel layer has a thickness ranging from 1 μm to 30 mm.9. A cell culture method device ...

Azlactone based thermally crosslinkable polymer coating for controlling cell behavior

Random copolymers, crosslinked thin films of the random copolymers and cell culture substrates comprising the crosslinked thin films are provided. Also provided are methods of making and using the copolymers, thin films and substrates. The copolymers are polymerized from glycidyl methacrylate monomers and vinyl azlactone monomers. The crosslinked thin films are substrate independent, in that they need not be covalently bound to a substrate to form a stable film on the substrate surface.

GRAPHENE OXIDE-BASED POROUS 3D MESH

A method of making a porous three-dimensional graphene mesh includes combining a graphene-containing material and a polymer having a plurality of hydroxyl groups in an alcohol solvent to form a mixture, adding a salt to the mixture, heating the mixture to form a gel, and washing the gel with water to remove the salt from the gel, leaving behind stable pores to form a scaffold. A three-dimensional porous graphene mesh includes a graphene-containing material and a polymer. The polymer is crosslinked with the graphene-containing material such that the Young's Modulus of the mesh is at least about 5 GPa. 1. A method of making a porous three-dimensional graphene mesh , the method comprising:combining a graphene-containing material and a polymer having a plurality of hydroxyl groups in an alcohol solvent to form a mixture;adding a salt to the mixture;heating the mixture to form a gel; andwashing the gel with water to remove the salt from the gel leaving behind stable pores to form a scaffold.2. The method of claim 1 , wherein the graphene-containing material comprises graphene oxide (GO).3. The method of claim 2 , wherein the graphene-containing material comprises a dispersion of graphene oxide (GO) in ethanol.4. The method of claim 1 , wherein the polymer is polyethylene glycol (PEG).5. The method of claim 4 , wherein the PEG has a molecular weight between 6000 and 8000 daltons.6. The method of claim 1 , wherein the mixture is heated to a temperature between about 60° C. and about 85° C. for between about 1 hour and about 36 hours to form the gel.7. The method of claim 1 , further comprising:drying the gel at a temperature between about 40° C. and about 70° C. for between about 1 hour and about 24 hours.8. The method of claim 1 , wherein the graphene-containing material and the polymer are combined at a graphene:polymer weight ratio between 1:1 and 1:3.9. The method of claim 1 , wherein the salt is added to the mixture such that the salt to graphene-containing material ...

CELLULAR RESPONSE TO SURFACE WITH NANOSCALE HETEROGENEOUS RIGIDITY

An elastomeric substrate comprises a surface with regions of heterogeneous rigidity, wherein the regions are formed by exposing the elastomeric substrate to an energy source to form the regions such that the regions include a rigidity pattern comprising spots. 1. An elastomeric substrate comprising a surface with regions of heterogeneous rigidity, wherein the regions are formed by exposing the elastomeric substrate to an energy source to form the regions such that the regions include a rigidity pattern comprising spots. This application is a continuation of and claims the benefit of priority under 35 U.S.C. §120 to U.S. patent application Ser. No. 14/523,586, filed on Oct. 24, 2014, which claims the benefit of priority under 35 U.S.C. §119(e) to U.S. Provisional Application Ser. No. 61/895,068, filed on Oct. 24, 2013, and is a continuation-in-part under 35 U.S.C. §120 of U.S. patent application Ser. No. 12/936,025, which is a U.S. National Stage Filing under 35 U.S.C. §371 from International Application No. PCT/US2009/002069, filed Apr. 2, 2009 and published as WO 1009/123739 A1 on Oct. 8, 2009, which claimed priority under 35 U.S.C. §119(e) to U.S. Provisional Application Ser. No. 61/072,717, filed on Apr. 2, 2008, each of which are incorporated herein by reference in their entireties.This invention was made with Government support under CHE0641523 awarded by the National Science Foundation (NSF) and under PN2EY016586 awarded by the National Institutes of Health (NIH) Common Fund Nanomedicine program. The Government has certain rights in the invention.The physical properties of a cell's environment are important factors in determining cell behavior and ultimately, phenotype. Among these factors, matrix rigidity can affect cell growth, differentiation and adhesion and motility. Alteration of the cellular rigidity sensing mechanism can be implicated in malignant transformation and tumerogenesis. Many aspects of the cellular rigidity-sensing mechanism are of interest, ...

Cell culture container, cell culture system, cell culture kit, and cell culture method

To provide a cell culture container and a cell culture system that can perform cell sorting, culturing, cell processing, and the like in one space and a volume of the space can be varied to suit respective steps. A cell culture container includes first molecules each bondable to target cells to be cultured, being immobilized to the container via a stimulus degradable linker, the container having a variable volume. A cell culture system included a cell culture container, including first molecules each bondable to target cells to be cultured, being immobilized to the container via a stimulus degradable linker, the container having a variable volume, and a stimulus imparting device that imparts a stimulus to the stimulus degradable linker

METHOD FOR MANUFACTURING THREE-DIMENSIONAL CELL CULTURE SUPPORT HAVING DOUBLE CROSSLINK, AND CASTING TRAY FOR MANUFACTURING THREE-DIMENSIONAL CELL CULTURE SUPPORT

The present disclosure relates to a method for manufacturing a three-dimensional cell culture support having a double crosslink, and a casting tray for manufacturing the three-dimensional cell culture support, wherein the method for manufacturing the three-dimensional cell culture support having the double crosslink includes: producing a cell mixed hydrogel; manufacturing a casting gel mold in a three-dimensional shape; and manufacturing a structure gelated in a three-dimensional shape, and the casting tray for manufacturing the three-dimensional cell culture support includes: a tray part including a groove accommodating a gel solution; a mold part covering the tray part; and a mold protrusion provided on the mold part and inserted into the groove when the mold part covers the tray part. 1. A method for manufacturing a three-dimensional cell culture support having a double crosslink , comprising:producing a cell mixed hydrogel;manufacturing a casting gel mold in a three-dimensional shape; anddispersing the cell mixed hydrogel into the casting gel mold manufactured in the three-dimensional shape and gelating the cell mixed hydrogel to manufacture a structure gelated in a three-dimensional shape.2. The method of claim 1 , wherein the producing of the cell mixed hydrogel comprises:mixing gelatin with alginate to prepare a mixed solution;filtering the mixed solution to produce a hydrogel; andmixing the hydrogel with cells.3. The method of claim 2 , wherein the mixed solution is one selected from a group consisting of apatite claim 2 , cellulose claim 2 , gellan claim 2 , agarose claim 2 , chitosan claim 2 , keratin claim 2 , and collagen claim 2 , or claim 2 , a combination of two or more of apatite claim 2 , cellulose claim 2 , gellan claim 2 , agarose claim 2 , chitosan claim 2 , keratin claim 2 , and collagen.4. The method of claim 2 , wherein the mixed solution is one selected front a group consisting of a transforming growth factor (TGF) claim 2 , a vascular ...

Spontaneously beating cardiac organoid constructs and integrated body-on-chip apparatus containing the same

A method of making a cardiac construct is carried out by depositing a mixture comprising live mammalian cardiac cells (e.g., individual cells, organoids, or spheroids), fibrinogen, gelatin, and water on a support to form an intermediate cardiac construct; optionally co-depositing a structural support material (e.g., polycaprolactone) with the mixture in a configuration that supports the intermediate construct; and then contacting thrombin to the construct in an amount effective to cross-link the fibrinogen and produce a cardiac construct comprised of live cardiac cells that together spontaneously beat in a fibrin hydrogel. Constructs made and methods of using the same are also described.

HYDROGEL COMPOSITIONS FOR USE IN CELL EXPANSION AND DIFFERENTIATION

Hydrogel compositions and methods of using hydrogel compositions are disclosed. Advantageously, the hydrogel compositions offer the ability to promote cellular expansion and/or cellular differentiation of various cells. 1. A method of promoting cellular expansion , the method comprising:preparing a hydrogel composition, wherein the hydrogel composition comprises a polyethylene glycol functionalized with norbornene, a crosslinking peptide, and a cell adhesion peptide;contacting a cell the hydrogel composition; andculturing the cell.2. The method of wherein the polyethylene glycol functionalized with norbornene comprises an 8-arm claim 1 , 20 kDa polyethylene glycol functionalized with norbornene.3. The method of wherein the cell is a circulating angiogenic cell.4. The method of wherein the hydrogel composition comprises at least 1 mM cell adhesion peptide selected from the group consisting of CRGDS (SEQ ID NO: 2) claim 3 , Acetylated-GCYGRGDSPG (SEQ ID NO:31) claim 3 , cyclic RGD (SEQ ID NO:35) claim 3 , CRGD-(G)-PHSRN (SEQ ID NO:29) claim 3 , and CPHSRN-(SG)-RGD (SEQ ID NO:30).5. The method of wherein the hydrogel composition comprises a shear modulus range of from about 2 kPa to about 12 kPa.6. The method of wherein the cell is a human mesenchymal stem cell.7. The method of wherein the hydrogel composition comprises a shear modulus of from about 1.8 kPa to about 33 kPa.8. The method of wherein the hydrogel composition comprises at least 0.25 mM of cell adhesion peptide selected from the group consisting of CRGDS (SEQ ID NO: 2) claim 6 , Acetylated-GCYGRGDSPG (SEQ ID NO:31) claim 6 , cyclic RGD (SEQ ID NO:35) claim 6 , CRGD-(G)-PHSRN (SEQ ID NO:29) claim 6 , and CPHSRN-(SG)-RGD (SEQ ID NO:30).9. The method of wherein the cell is a human pluripotent stem cell selected from the group consisting of a human embryonic stem cell and human induced pluripotent stem cell.10. The method of wherein the hydrogel composition comprises at least 0.25 mM of cell adhesion peptide ...

APPARATUS FOR BUILDING COMPLEX 3D BIOMIMETIC SCAFFOLDS

A system and apparatus for constructing complex three-dimensional scaffolds that takes advantage of the physical and chemical properties of gelatin-sugar hydrogels. Novel apparatus for building complex three-dimensional scaffolds for biomimetic applications such as in vitro organ growth, using a gelatin/sugar/water gel, ultraviolet radiation, and heat or enzyme are described. The apparatus produce gelatin-sugar hydrogels demonstrating greater thermal stability, mechanical strength, and resistance to enzymatic degradation. The invention also provides a means to assemble the gelatin sugar hydrogel films into complex three-dimensional structures (scaffolds). To account for the native biochemical factors present in natural scaffolds, methods of conjugating such factors to the gelatin-sugar hydrogel are described. These scaffolds can then be applied for tissue culturing and organ growth. 1. An apparatus for building three dimensional biomimetic scaffolds comprising a plurality of processing units treating a mixture of gelatin and water with UV radiation to produce a biomimetic scaffold having a plurality of cross-linked gel layers.2. An apparatus for building three dimensional biomimetic scaffolds comprising a plurality of processing units treating a mixture of gelatin , sugar , and water with UV radiation to produce a biomimetic scaffold having a plurality of cross-linked gel layers.3. The apparatus of wherein each said processing unit performs one or more of the following steps: (a) selectively irradiating said mixture to form cross-linked gel layers having at least one non-irradiated region; (b) removing the non-irradiated material from the non-irradiated regions to leave cross-linked gel layers demonstrating a predetermined irregular shape; and (c) fusing a plurality of said cross-linked gel layers together to form a biomimetic scaffold.4. The apparatus of wherein one of the processing units performs the additional step of conjugating select biochemical factors to ...

Novel method for forming hydrogel arrays using surfaces with differential wettability

Patterned hydrogel arrays and methods of preparing patterned hydrogel arrays are disclosed. Advantageously, the methods used to prepare the patterned hydrogel arrays allow for controlling individual hydrogel spot conditions such as hydrogel spot modulus, hydrogel spot ligand identity and hydrogel spot ligand density, which allows for preparing a wide range of hydrogel spots in a single array format. Patterned hydrogel arrays can also be formed to include hydrogel-free pools surrounded by hydrogel. Additionally, the patterned hydrogel arrays of the present disclosure support the culture of a range of cell types. The patterned hydrogel arrays offer the ability to rapidly screen substrate components for influencing cell attachment, spreading, proliferation, migration, and differentiation.

Manufacturing Process for Polysaccharide Beads

The invention discloses a method of manufacturing polysaccharide beads, comprising the steps of: i) providing a water phase comprising an aqueous solution of a polysaccharide; ii) providing an oil phase comprising at least one water-immiscible organic solvent and at least one oil-soluble emulsifier; iii) emulsifying the water phase in the oil phase to form a water-in-oil (w/o) emulsion; and iv) inducing solidification of the water phase in the w/o emulsion, wherein the organic solvent is an aliphatic or alicyclic ketone or ether. 1. A method of manufacturing polysaccharide beads , comprising the steps of:i) providing a water phase comprising an aqueous solution of a polysaccharide;ii) providing an oil phase comprising at least one water-immiscible organic solvent and at least one oil-soluble emulsifier;iii) emulsifying said water phase in said oil phase to form a water-in-oil (w/o) emulsion; andiv) inducing solidification of said water phase in said w/o emulsion,wherein said at least one organic solvent is an aliphatic or alicyclic ketone or ether.2. A method of manufacturing polysaccharide beads , comprising the steps of:i) providing a water phase comprising an aqueous solution of a polysaccharide;ii) providing an oil phase comprising at least one water-immiscible organic solvent and at least one oil-soluble emulsifier;iii) emulsifying said water phase in said oil phase to form a water-in-oil (w/o) emulsion; andiv) inducing solidification of said water phase in said w/o emulsion,{'sup': 1/2', '1/2', '1/2', '1/2', '1/2', '1/2, 'wherein said at least one organic solvent does not contain halogens and has Hansen solubility parameter values in the ranges of δD=15.0-18.5 MPa, δP=3.5-8.5 MPaand δH=4.0-5.5 MPa, or wherein said oil phase comprises a mixture of halogen-free water-immiscible organic solvents, said mixture having Hansen solubility parameter values in the ranges of δD=15.0-18.5 MPa, δP=3.5-8.5 MPaand δH=4.0-5.5 MPa.'}3. The method of wherein said at least one ...

IN VITRO PLATFORM AND METHODS FOR CULTURING EMBRYOS FOR IMPLANTATION

A mammalian in vitro system for culturing an embryo includes a collagen or fibrin matrix and endometrial and/or stromal cells. The in vitro platforms and methods according to embodiments of the invention allow for in vitro embryonic development (including implantation) prior to transfer of the embryo complex in vivo for further development. 1. A method of culturing a mammalian embryo derived from a first uterus for implantation into a second uterus , the method comprising:adding endometrial cells harvested from the first uterus to a collagen or fibrin matrix to form an endometrial-collagen matrix or an endometrial-fibrin matrix; andadding an isolated embryo derived from the first uterus to the endometrial-collagen matrix or the endometrial-fibrin matrix to form an in vitro embryo culture complex.2. The method of claim 1 , wherein the isolated embryo is at mammalian embryological Stage 2 claim 1 , 3 claim 1 , or 4.3. The method of claim 1 , wherein the embryo is a blastocyst.4. The method of claim 1 , wherein the collagen matrix comprises a polymerized collagen gel or an insoluble collagen.5. The method of claim 4 , wherein the polymerized collagen gel comprises Type I claim 4 , Type III claim 4 , Type IV claim 4 , Type V collagen claim 4 , or combinations thereof.6. The method of claim 4 , wherein the insoluble collagen is a crosslinked collagen sheet.7. The method of claim 1 , wherein the endometrial cells harvested from the first uterus are harvested by trypsinization of an endometrium of the first uterus.8. The method of claim 1 , further comprising incubating the in vitro embryo culture complex until the isolated embryo attaches to the endometrial-collagen matrix or the endometrial-fibrin matrix to form an attached in vitro embryo complex.9. The method of claim 8 , wherein the incubating comprises immersing the in vitro embryo culture complex in media comprising serum.10. The method of claim 9 , wherein the serum is plasma-derived serum and/or cord blood serum. ...

ENCAPSULATION AND CARDIAC DIFFERENTIATION OF HIPSCS IN 3D PEG-FIBRINOGEN HYDROGELS

The present invention relates to the production of cell cultures and tissues from undifferentiated pluripotent stem cells using three-dimensional biomimetic materials. The resultant cell cultures or tissues can be used in any of a number of protocols including testing chemicals, compounds, and drugs. Further, the methods and compositions of the present invention further provide viable cell sources and novel cell delivery platforms that allow for replacement of diseased tissue and engraftment of new cardiomyocytes from a readily available in vitro source. The present invention includes novel methods required for the successful production of cell cultures and tissues, systems and components used for the same, and methods of using the resultant cell and tissue compositions. 120.-. (canceled)21. A three-dimensional , synchronously contracting cardiac tissue comprising;a hydrogel material comprising a covalently crosslinkable component and a natural hydrogel component, the natural hydrogel component comprising one or more of fibrinogen, collagen, gelatin, hyaluronic acid, elastin, fibronectin, laminin, fibrin, alginate, and decellularized cardiac extracellular matrix, andthree-dimensionally differentiated, PSC-derived cardiomyocytes encapsulated within the hydrogel material.22. The three-dimensional claim 21 , synchronously contracting cardiac tissue of claim 21 , wherein the synchronously contracting cardiac tissue contracts as a single unit.23. The three-dimensional claim 22 , synchronously contracting cardiac tissue of claim 22 , wherein the synchronously contracting cardiac tissue contracts spontaneously.24. The three-dimensional claim 23 , synchronously contracting cardiac tissue of claim 23 , wherein the synchronously contracting cardiac tissue contracts spontaneously without stimulation.25. The three-dimensional claim 23 , synchronously contracting cardiac tissue of claim 23 , wherein the spontaneous contraction frequency ranges from 0.59 to 1.53 Hertz.26. The ...

Encapsulated liver tissue

The present disclosure provides an encapsulated liver tissue that can be used in vivo to improve liver functions, in vitro to determine the hepatic metabolism and/or hepatotoxicity of an agent and ex vivo to remove toxic compounds from patients' biological fluid. The encapsulated liver tissue comprises at least one liver organoid at least partially covered with a biocompatible cross-linked polymer. Processes for making the encapsulated liver tissue are also provided.

EB Matrix Production from Fetal Tissues and its Use for Tissue Repair

A method of performing and preserving a bioremodelable, biopolymer scaffold material by subjecting animal tissue to chemical and mechanical processing. In addition to skin tissue, another source of EBM is a blood vessel. EBM may be used for hernia repair, colon, rectal, vaginal and or urethral prolapse treatment; pelvic floor reconstruction; muscle flap reinforcement; lung tissue support; rotator cuff repair or replacement; periosteum replacement; dura repair; pericardial membrane repair; soft tissue augmentation; intervertebral disk repair; and periodontal repair. EBM may also be used as a urethral sling, laminectomy barrier or spinal fusion device. 1. A method for producing and preserving a biopolymer scaffold material , comprising the steps of:a. harvesting tissue from an animal source;b. optionally extracting growth and differentiation factors from said tissue;c. inactivating infective agents of said tissue;d. mechanically expressing undesirable components from said tissue;e. delipidizing said tissue;f. washing said tissue for removal of chemical residues;g. optionally drying said tissue; andh. optionally cross-linking said tissue.231.-. (canceled) This application is a continuation-in-part application of U.S. application Ser. No. 09/871,518, filed May 31, 2001, the entire contents of which are herein incorporated by reference.This invention relates to the field of tissue engineering, and in particular to animal-derived, bioremodelable, biopolymer scaffold materials used to repair animal tissue. The term “bioremodelable” or “bioremodelability” refers to a material that lends itself to the breakdown by cells that occupy it and use it as a template for creating a replacement made up mainly of newly synthesized components secreted by the cells.Rebuilding the human body is a significant industry. Human tissue banks and synthetic polymers do not meet the need for repair or replacement of body parts. High on the list of alternative sources of material used to meet ...

Method of preparing polyvinyl alcohol nanofiber membrane enhancing cell specific adhesion

A method of preparing a polyvinyl alcohol nanofiber membrane includes a material for controlling cell specific adhesion, and a nanofiber membrane that can maintain cellular functions such as cell activity and growth is prepared by adding aqueous solutions containing a polyacrylic acid and a glutaraldehyde crosslinking agent in a polyvinyl alcohol and materials capable of enhancing or regulating cell adhesion, electrospinning, treating with hydrochloric acid vapor and dimethylformaldehyde solvent and treating with sodium hydroxide to control the cell adhesion.