Поиск патентов

05-01-2012 дата публикации

Bone-like prosthetic implants

Номер: US20120003185A1

Автор: Shai Meretzki

Принадлежит: Individual

A prosthetic implant comprising a biocompatible three-dimensional scaffold and at least two cell types selected from the group consisting of osteoblasts, osteoclasts, and endothelial cells or progenitors thereof.

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Номер записи: 1

17-05-2012 дата публикации

Nanotopographic compositions and methods for cellular organization in tissue engineered structures

Номер: US20120122222A1

Автор: David Carter, Jeffrey T. Borenstein, Joseph P. Vacanti

Принадлежит: Charles Stark Draper Laboratory Inc, General Hospital Corp

The present invention relates to tissue engineered compositions and methods comprising nanotopographic surface topography (“nanotopography”) for use in modulating the organization and/or function of multiple cell types.

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Номер записи: 2

07-06-2012 дата публикации

Umbilical cord amniotic membrane products

Номер: US20120141595A1

Автор: Amy Tseng, Ek Kia Tan, Scheffer Tseng

Принадлежит: TissueTech Inc

Disclosed herein, in certain instances, are tissue grafts derived from UCAM. Further disclosed herein, in certain instances, are use for tissue grafts derived from UCAM.

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Номер записи: 3

13-09-2012 дата публикации

Tissue transplant compositions and methods for use

Номер: US20120230966A1

Автор: John M. Garvey, Keith D. Crawford, Pamela Layton

Принадлежит: Brigham and Womens Hospital Inc, PARCELL LABS LLC

Provided are transplants and methods for augmenting formation and restoration of organ and tissue, for example, bone formation, by administering autologous or allogeneic human embryonic-like adult stem cells (ELA cells). Also provided is a method for augmenting formation of tissues and organs by administering a transplant having ELA stem cells or combination of ELA stem cells.

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Номер записи: 4

27-09-2012 дата публикации

Mesh enclosed tissue constructs

Номер: US20120244617A1

Автор: Arash Kheradvar, Seyedhamed Alavi

Принадлежит: UNIVERSITY OF CALIFORNIA

Described is a scaffold that is strong enough to resist forces that exist inside a body, while possessing biocompatible surfaces. The scaffold is formed of a layer of mesh (e.g., Stainless Steel or Nitinol) that is tightly enclosed by a multi-layer biological matrix. The biological matrix can include three layers, such a first layer (smooth muscle cells) formed directly on the metal mesh, a second layer (fibroblast/myofibroblast cells) formed on the first layer, and a third layer (endothelial cells) formed on the second layer. The scaffold can be formed to operate as a variety of tissues, such as a heart valve or a vascular graft. For example, the mesh and corresponding biological matrix can be formed as leaflets, such that the scaffold is operable as a tissue heart valve.

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Номер записи: 5

03-01-2013 дата публикации

Artificial skin

Номер: US20130006355A1

Автор: Eijiro Adachi, Kenichi Umishio, Makoto Tsunenaga, Shinji Inomata, Shunsuke Iriyama

Принадлежит: Shiseido Co Ltd

The present invention relates to a method for producing artificial skin, comprising: adding a matrix metalloproteinase inhibitor and a heparanase inhibitor to an artificial skin formation culture medium comprising human epidermal keratinocytes and human dermal fibroblasts, culturing the cells in the artificial skin formation culture medium, and forming artificial skin.

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Номер записи: 6

25-04-2013 дата публикации

Method For Restoring Alveolar Bone Via Transplant of a Regenerated Tooth Unit

Номер: US20130101951A1

Автор: Kazuhisa Nakao, Masamitsu Oshima, Takashi Tsuji

Принадлежит: Organ Technologies Inc

The object of the present invention is to provide a method for restoring the alveolar bone of a mammal with a missing tooth. The present invention provides a method for restoring the alveolar bone in a mammal with a missing tooth comprising a step of transplanting a regenerated tooth unit to the said missing site. The regenerated tooth unit is characterized in that it has a periodontal tissue portion in addition to a tooth crown portion.

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Номер записи: 7

27-06-2013 дата публикации

PLATFORM FOR ENGINEERED IMPLANTABLE TISSUES AND ORGANS AND METHODS OF MAKING THE SAME

Номер: US20130164339A1

Автор: Dorfman Scott, Khatiwala Chirag, Murphy Keith, Presnell Sharon, Shepherd Benjamin

Принадлежит: ORGANOVO, INC.

Disclosed are engineered tissues and organs comprising one or more muscle cell-containing layers, the engineered tissue or organ consisting essentially of cellular material, provided that the engineered tissue or organ is implantable in a vertebrate subject and not a vascular tube. 1. A living , three-dimensional engineered tissue or organ comprising one or more layers , the one or more layers characterized by one or more of: a) substantially scaffold-free at the time of use; and b) bioprinted , the one or more layers suitable for implantation in a vertebrate subject upon sufficient maturation; provided that at least one layer of the engineered tissue or organ comprises muscle cells and that the engineered tissue or organ is not a vascular tube.2. The tissue or organ of claim 1 , wherein at least one layer comprises a plurality of cell types claim 1 , the cell types spatially arranged relative to each other to create a planar geometry.3. The tissue or organ of claim 2 , wherein at least one layer is at least 100 μm thick in its smallest dimension at the time of fabrication.4. The tissue or organ of claim 1 , comprising a plurality of layers claim 1 , at least one layer compositionally or architecturally distinct from at least one other layer to create a laminar geometry.5. The tissue or organ of claim 4 , wherein at least one layer is at least 100 μm thick in its smallest dimension at the time of fabrication.6. The tissue or organ of claim 1 , wherein the tissue or organ is a sac claim 1 , sheet claim 1 , or tube claim 1 , wherein said tube is not a vascular tube.7. The tissue or organ of claim 1 , wherein the tissue or organ is substantially free of any pre-formed scaffold at the time of use.8. The tissue or organ of claim 1 , wherein the tissue or organ is bioprinted.9. The tissue or organ of claim 1 , wherein the one or more layers generates an extracellular matrix.10. The tissue or organ of claim 1 , wherein the muscle cells are smooth muscle cells.11. The ...

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Номер записи: 8

15-08-2013 дата публикации

HAIR FOLLICLE NEOGENESIS

Номер: US20130209427A1

Автор: Darling Thomas N., LI Shaowei, Thangapazham Rajesh

Принадлежит:

This invention provides a skin substitute comprising epithelial cells and modified mesenchymal cells, wherein the modified mesenchymal cells have decreased TSC1/TSC2 function, increased mTORCI function, and/or decreased mTORC2 function compared to wild type mesenchymal cells, and methods for using the same. This invention also provides a method for transplanting cells capable of inducing hair follicles, comprising subdermally or intradermally delivering to a patient modified mesenchymal cells, wherein the modified mesenchymal cells have decreased TSC1/TSC2 function, increased mTORCI function, and/or decreased mTORC2 function compared to wild type mesenchymal cells. 1. A skin substitute comprising epithelial cells and modified mesenchymal cells , wherein , compared to wild type mesenchymal cells , the modified mesenchymal cells have:(a) a decreased TSC1/TSC2 complex function and/or(b) an increased mTORC1 function, a decreased mTORC2 function, or both, through mimetics of decreased TSC1/TSC2 function.2. The skin substitute of claim 1 , wherein the modified mesenchymal cell comprises:(a) a downregulated TSC1 or TSC2;(b) an upregulated inhibitory protein that inhibits TSC1/TSC2 function or acts as a mimetic of decreased TSC1/TSC2 function; or(c) a downregulated stimulatory protein that stimulates TSC1/TSC2 function or acts as a mimetic of increased TSC1/TSC2 function.3. The skin substitute of claim 2 , wherein at least one of Ras claim 2 , Raf claim 2 , Mek claim 2 , Erk claim 2 , Rsk1 claim 2 , PI3K claim 2 , Akt1 claim 2 , Akt2 claim 2 , Akt3 claim 2 , Rheb claim 2 , mTOR claim 2 , Raptor claim 2 , Rictor claim 2 , mLST8 claim 2 , S6K1 claim 2 , ribosomal protein S6 claim 2 , SKAR claim 2 , SREBP1 claim 2 , elF4e claim 2 , IKKbeta claim 2 , Myc claim 2 , Runx1 claim 2 , or p27 is upregulated claim 2 , and/orat least one of TSC1, TSC2, CYLD, FLCN, MEN1, NF1, PTEN, PRAS40, 4E-BP1, GSK3, or Deptor is down-regulated.4. The skin substitute of claim 3 , wherein TSC2 is down ...

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Номер записи: 9

26-12-2013 дата публикации

Methods of using regenerative cells in the treatment of renal diseases and disorders

Номер: US20130344035A1

Автор: Eric Daniels, John K. Fraser, Marc H. Hedrick

Принадлежит: Cytori Therapeutics Inc

Cells present in processed lipoaspirate tissue are used to treat patients, including patients with renal conditions, diseases or disorders. Methods of treating patients include processing adipose tissue to deliver a concentrated amount of stem cells obtained from the adipose tissue to a patient. The methods may be practiced in a closed system so that the stem cells are not exposed to an external environment prior to being administered to a patient. Accordingly, in a preferred method, cells present in processed lipoaspirate are placed directly into a recipient along with such additives necessary to promote, engender or support a therapeutic renal benefit.

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Номер записи: 10

27-03-2014 дата публикации

COMPOSITIONS AND METHODS FOR PROMOTING TISSUE REGENERATION

Номер: US20140086891A1

Автор: Robertson Brooklyn, Sandstad Jesse H.

Принадлежит: PROGENICARE, LLC

Provided are compositions for promoting bone and cartilage growth. In certain embodiments, tissue graft compositions comprising a polymeric scaffold (e.g., PLGA), hyaluronic acid, and substantially purified mononucleated cells derived from bone marrow aspirate. In various embodiments, the tissue graft composition may comprise thrombin. The tissue grafts may be used to promote bone growth, e.g., in a spinal fusion operation. 1. A tissue graft material comprising:(i) a natural or synthetic scaffold;(ii) hyaluronic acid or hylauronate;(iii) substantially purified or concentrated cells, wherein the cells are mononucleated cells derived from bone marrow or cells from adipose tissue; and(iv) substantially purified or concentrated platelets.2. The tissue graft of claim 1 , wherein the composition comprises about 1 to 50% hyaluronic acid.3. The tissue graft of claim 2 , wherein the composition comprises about 7 to 20% hyaluronic acid.4. The tissue graft of claim 3 , wherein the composition comprises about 8 to 14% hyaluronic acid.5. The tissue graft of claim 1 , wherein the tissue graft material further comprises thrombin.6. The tissue graft of claim 5 , wherein the thrombin is selected from the group consisting of thrombin/CaCland thrombin/NaCl.7. The tissue graft of claim 6 , wherein the thrombin is thrombin/CaCl.8. The tissue graft of claim 5 , wherein the thrombin is selected from the group consisting of bovine thrombin claim 5 , procine thrombin claim 5 , and autologous human thrombin.9. The tissue graft of claim 5 , wherein the composition comprises from about 1 u/mL to about 500 u/mL.10. The tissue graft of claim 9 , wherein the composition comprises from about 50 u/mL to about 150 u/mL.11. The tissue graft of claim 1 , wherein the mononuclear cells comprise purified or concentrated endothelial progenitor cells claim 1 , hematopoietic stem cells claim 1 , or mesenchymal stem cells.12. The tissue graft of claim 11 , wherein the mononuclear cells comprise purified or ...

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Номер записи: 11

03-01-2019 дата публикации

COMPOSITIONS AND METHODS FOR THE GENERATION OF MELANOCYTES THROUGH DIRECT REPROGRAMMING

Номер: US20190002827A1

Автор: Xu Xiaowei, Yang Ruifeng

Принадлежит:

Compositions and methods for generating melanocytes through direct reprogramming are disclosed. Also disclosed are methods of use of such compositions for the treatment of vitiligo and other hypopigmentation disorders. In accordance with the present invention, a method for producing melanocytes suitable for use in human patients is provided. An exemplary method comprises providing cells capable of transdifferentiation into melanocytes, culturing said cells in a chemically defined culture medium, introducing at least two of microphthalmia-associated transcriptiokn factor (MITF), SRY-related HMG-box (SOX10) transcription factor and paired box-3 (PAX-3) transcription factor and paired box-3 (PAX-3) transcription factor, or nucleic acids encoding said transcription factors into said cells, wherein expression of said factors induces the cells to transdifferentiae into melanocytes expressing melanocyte markers TYR, DCT, S-100 and Melan-A. 1. A method for producing melanocytes comprising:a) providing cells capable of transdifferentiation into melanocytes;b) culturing said cells in a chemically defined culture medium;c) introducing at least two of microphthalmia-associated transcription factor (MITF), SRY-related HMG-box (SOX10) transcription factor and paired box-3 (PAX-3) transcription factor, or nucleic acids encoding said transcription factors into said cells, thereby inducing said cells to transdifferentiae into melanocytes expressing melanocyte markers TYR, DCT, S-100 and Melan-A; and, optionallyd) isolating said melanocytes.2. The method of claim 1 , wherein all three transcription factors are introduced and said cells are fibroblasts.3. The method of claim 1 , wherein said cells are mammalian in origin.4. The method of claim 3 , wherein said cells are human in origin.5. The method of claim 2 , wherein said cells are fetal or adult fibroblasts.6. (canceled)7. The method of claim 1 , wherein said transcription factors are encoded by one or more recombinant expression ...

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Номер записи: 12

20-01-2022 дата публикации

Dermal substitutes and engineered skin with rete ridges

Номер: US20220016321A1

Автор: Britani Blackstone, Heather Powell, John Bailey

Принадлежит: Ohio State Innovation Foundation

Disclosed herein are dermal substitutes comprising: fibroblasts positioned in a biologically compatible matrix, the biologically compatible matrix comprising a plurality of protrusions on at least one surface; wherein the plurality of protrusions comprise a length and width sufficient to improve a dermal graft outcome. Also disclosed are methods of treating a skin wound on a subject, the method comprising: contacting a skin wound with a herein disclosed dermal substitute. Also disclosed are methods of preparing a dermal graft for transplantation, the method comprising: culturing fibroblasts positioned in a biologically compatible matrix in a scaffold comprising a plurality of protrusions on at least one surface; wherein the scaffold comprises a plurality of protrusions comprising a length and width sufficient to improve a dermal graft outcome.

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Номер записи: 13

14-01-2021 дата публикации

IMPLANT MATERIALS FOR TMJ REPAIR, METHODS OF MAKING THE IMPLANT MATERIALS FOR TMJ REPAIR, AND METHOD OF USING IMPLANT MATERIALS FOR TMJ REPAIR

Номер: US20210007850A1

Автор: McFetridge Peter S.

Принадлежит:

In accordance with the purpose(s) of the present disclosure, as embodied and broadly described herein, embodiments of the present disclosure, in one aspect, relate to TMJ implantation materials and implants (e.g., temporomandibular joint (TMJ) disc), methods of making TMJ implantation materials and implants, methods of forming a TMJ implantation material or an implant, and the like. 1. A temporomandibular joint (TMJ) disc , comprising:a TMJ scaffold structure comprising a freeze-dried or previously freeze-dried, decellularized fibrocartilage tissue from a subject animal, the TMJ scaffold structure having a plurality of drilled holes in the scaffold structure.2. The TMJ disc of claim 1 , wherein the TMJ scaffold structure has a compressive modulus and a peak stress value less than that of a corresponding sodium dodecyl sulfate (SDS) decellularized fibrocartilage tissue that has never been freeze-dried.3. The TMJ disc of claim 1 , further comprising one or more populations of added cells claim 1 , wherein a portion of the cells are in the holes of the TMJ scaffold structure.4. The TMJ disc of claim 3 , wherein the population of cells is selected from the group consisting of: stem cells claim 3 , endothelial cells claim 3 , smooth muscle cells claim 3 , fibroblasts claim 3 , and combinations thereof.5. The TMJ disc of claim 3 , wherein the population of cells is a homogeneous population of cells.6. The TMJ disc of claim 3 , wherein the population of cells is a heterogenous population of cells.7. The TMJ disc of claim 1 , wherein the TMJ scaffold structure is substantially free of non-TMJ tissue.8. The TMJ disc of claim 1 , wherein the holes have a diameter of about 1 to 500 micrometers.9. The TMJ disc of claim 1 , wherein one or more pairs of holes are spaced by about 1 micrometer to 10 millimeters.10. The TMJ disc of claim 1 , wherein the holes are through the scaffold structure claim 1 , the holes are only partially through the scaffold structure claim 1 , or a ...

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Номер записи: 14

11-01-2018 дата публикации

ADHERENT STROMAL CELLS DERIVED FROM PLACENTAS OF MULTIPLE DONORS AND USES THEREOF

Номер: US20180008649A1

Автор: Aberman Zami, Burger Ora, MERETZKI Shai

Принадлежит:

Pharmaceutical compositions comprising adherent stromal cells (ASCs) are provided. The ASCs are obtained from at least two donors. Articles of manufacture comprising the pharmaceutical compositions together with a delivery device for administering the ASCs to a subject are also provided. Also provided are methods of treating various diseases and conditions that are treatable by administering ASCs to a subject in need of treatment. 1. A method of treating at least one condition that can be treated by administration of placental-derived adherent stromal cells (ASCs) to a subject in need thereof , the method comprising administering to the subject an effective amount of adherent stromal cells (ASCs) , wherein the ASCs are negative for the marker CD200 , wherein the administered ASCs comprise ASCs from at least two donor placentas , wherein the at least two donors have at least two different HLA genotypes , and wherein the at least one condition is selected from stem cell deficiency , heart disease. a neurodegenerative disorder , cancer , stroke , burns , loss of tissue , loss of blood , anemia , an autoimmune disease , ischemia , skeletal muscle regeneration , neuropathic pain , a compromised hematopoietic system , geriatric diseases , and a medical condition requiring connective tissue regeneration and/or repair.2. The method of claim 1 , wherein the ASCs are obtained by a method comprising culturing placental-derived cells in a three-dimensional (3D) culture.3. The method of claim 2 , wherein the 3D culturing comprises culturing in a 3D bioreactor.4. The method of claim 3 , wherein cells in the 3D bioreactor are cultured under perfusion.5. The method of claim 3 , wherein the 3D bioreactor comprises at least one adherent material selected from a polyester and a polypropylene.6. The method of claim 1 , wherein the ASCs are positive for at least one marker selected from CD73 claim 1 , CD90 claim 1 , CD29 claim 1 , D7-FIB and CD105.7. The method of claim 6 , wherein the ...

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Номер записи: 15

21-01-2016 дата публикации

MICRO-TISSUE PARTICLES AND METHODS FOR THEIR USE IN CELL THERAPY

Номер: US20160015860A1

Автор: Kreutziger Kareen Louise, Murry Charles

Принадлежит:

In some embodiments, a micro-tissue particle comprising a scaffold-free population of aggregated cells is provided. The micro-tissue particle may have a diameter less than approximately 1 mm. In some aspects the diameter is less than approximately 500? m. The population of cells may include at least one terminally differentiated cell type. In one aspect, the population of cells may include cardiomyocytes, endothelial cells, smooth muscle cells, mesenchymal stem cells, or a combination thereof. The micro-tissue particle may be used to treat or regenerate an injured, degenerated or diseased tissue. For example, micro-tissue particles that include cardiomyocytes may be administered to myocardial tissue that has been injured due to a myocardial infarction.

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Номер записи: 16

17-01-2019 дата публикации

TISSUE-ENGINEERED GUT-SPHINCTER COMPLEXES AND METHODS OF MAKING THE SAME

Номер: US20190015190A1

Автор: BITAR Khalil

Принадлежит:

Methods are disclosed for forming tissue engineered, tubular gut-sphincter complexes from intestinal circular smooth muscle cells, sphincteric smooth muscle cells and enteric neural progenitor cells. The intestinal smooth muscle cells and neural progenitor cells can be seeded on a mold with a surface texture that induces longitudinal alignment of the intestinal smooth muscle cells and co-cultured until an innervated aligned smooth muscle sheet is obtained. The innervated smooth muscle sheet can then be wrapped around a tubular scaffold to form an intestinal tissue construct. Additionally, the sphincteric smooth muscle cells and additional enteric neural progenitor cells can be mixed in a biocompatiable gel solution, and the gel and admixed cells applied to a mold having a central post such that the sphinteric smooth muscle and neural progenitor cells can be cultured to form an innervated sphincter construct around the mold post. This innervated sphincter construct can also be transferred to the tubular scaffold such that the intestinal tissue construct and sphincter construct contact each other, and the resulting combined sphincter and intestinal tissue constructs can be further cultured about the scaffold until a unified tubular gut-sphincter complex is obtained. 1. A method of forming a tissue engineered , tubular gut-sphincter complex comprising:isolating intestinal circular smooth muscle cells from an intestinal donor source,isolating sphincteric smooth muscle cells from a sphincteric donor source,isolating enteric neural progenitor cells from at least one neural progenitor donor source,seeding the isolated intestinal circular smooth muscle cells on a mold with a surface texture that induces longitudinal alignment of the intestinal circular smooth muscle cells,adding the isolated enteric neural progenitor cells to the intestinal circular smooth muscle cells on the mold,co-culturing the intestinal circular smooth muscle cells and the enteric neural progenitor ...

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Номер записи: 17

17-01-2019 дата публикации

PATCH GRAFT COMPOSITIONS FOR CELL ENGRAFTMENT

Номер: US20190015556A1

Автор: Reid Lola M., Wauthier Eliane, Zhang Wencheng

Принадлежит: The University of North Carolina at Chapel Hill

Compositions and methods of transplanting cells by grafting strategies into solid organs (especially internal organs) are provided. These methods and compositions can be used to repair diseased organs or to establish models of disease states in experimental hosts. The method involves attachment onto the surface of a tissue or organ, a patch graft, a “bandaid-like” covering, containing epithelial cells with supporting early lineage stage mesenchymal cells. The cells are incorporated into soft gel-forming biomaterials prepared under serum-free, defined conditions comprised of nutrients, lipids, vitamins, and regulatory signals that collectively support stemness of the donor cells. The graft is covered with a biodegradable, biocompatible, bioresorbable backing used to affix the graft to the target site. The cells in the graft migrate into and throughout the tissue such that within a couple of weeks they are uniformly dispersed within the recipient (host) tissue. The mechanisms by which engraftment and integration of donor cells into the organ or tissue involve multiple membrane-associated and secreted forms of MMPs. 1. A method of treating a subject with a disease or disorder of the pancreas , the method comprising contacting the subject's pancreas with a patch graft comprising:(a) a mixed population having two or more cell types, at least one of which is at an early lineage stage that is capable of expressing membrane-associated and/or secreted matrix metalloproteinases (MMPs), said mixed population supported in a medium in a hydrogel having viscoelasticity sufficient to allow for migration of said mixed population towards and into a target tissue; and(b) a backing comprising a biocompatible, biodegradable material having a viscoelasticity sufficient to inhibit a migration of said mixed population in a direction away from the target tissue and through said backing or barrier, andallowing the cells contained in the patch graft to become incorporated into the pancreas, ...

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Номер записи: 18

28-01-2016 дата публикации

TISSUE ENGINEERED INTESTINE

Номер: US20160022873A1

Автор: Besner Gail E., JOHNSON Jed, Liu Yanchun

Принадлежит:

The invention provides for engineered intestinal construct and methods of making these constructs. The invention also provides for methods of treating short bowel syndrome or methods of repairing an intestine after resection comprising inserting an engineered intestinal construct into the intestine of a subject in need. 1. An engineered intestine construct comprising a nanofiber scaffold seeded with neural stem cells , smooth muscle cells and intestinal stem cells , and wherein the nanofiber scaffold comprises HB-EGF polypeptide or a fragment thereof.2. An engineered intestine construct comprising a nanofiber scaffold seeded with neural stem cells , smooth muscle cells and intestinal stem cells , wherein at least one of the neural stem cells , smooth muscle cells or intestinal stem cells overexpress HB-EGF polypeptide or a fragment thereof.3. An engineered intestine construct comprising a multilayer nanofiber scaffold ,wherein the multilayer nanofiber scaffold comprises at least an inner layer and an outer layer,wherein the outer layer comprises neural stem cells and smooth muscle cells, andwherein the inner layer comprises intestinal stem cells.4. The engineered intestine construct of wherein at least of the layers comprises HB-EGF polypeptide or a fragment.5. The engineered intestine construct of or wherein the construct further comprises at least one middle layer.65. The engineered intestine construct of any one of - wherein the nanofiber scaffold comprises Poly(glycolic acid)(PGA) nanofibers claims 1 , Poly(ε-caprolactone) (PCL) nanofibers claims 1 , Poly(-caprolactone-co-lactic acid) (PLC) nanofibers claims 1 , Poly(L-lactic acid) (PLLA) nanofibers claims 1 , Poly(D-lactic acid-co-glycolic acid) (PDLGA) nanofibers claims 1 , Poly(D-lactic acid-co-glycolic acid) (PLGA) nanofibers claims 1 , Polyurethane (PU) nanofibers claims 1 , Polydioxanone (PDO) nanofibers or a combination thereof.76. The engineered intestine construct of any one of - wherein the construct ...

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Номер записи: 19

31-01-2019 дата публикации

VASCULARIZED BIPHASIC TISSUE CONSTRUCTS

Номер: US20190030212A1

Автор: Cui Haitao, Zhang Lijie G., Zhu Wei

Принадлежит:

Biphasic tissue constructs that include a scaffold having one or more channels, a vascular portion comprising a hydrogel at least partially disposed in the one or more channels, and a first bioactive growth factor and a second bioactive growth factor different from the first bioactive growth factor, the first bioactive growth factor localized to the scaffold and the second bioactive growth factor localized to the vascular portion. The first bioactive growth factor may be bone morphogenetic protein 2 (BMP2) peptide and the second bioactive growth factor may be vascular endothelial growth factor (VEGF) peptide. 1. A biphasic tissue construct comprising:a scaffold having one or more channels;a vascular portion comprising a hydrogel, the vascular portion at least partially disposed in the one or more channels; anda first bioactive growth factor and a second bioactive growth factor different from the first bioactive growth factor, the first bioactive growth factor localized to the scaffold and the second bioactive growth factor localized to the vascular portion.2. The biphasic biomimetic tissue construct according to claim 1 , wherein the first bioactive growth factor is bone morphogenetic protein 2 (BMP2) peptide and the second bioactive growth factor is vascular endothelial growth factor (VEGF) peptide.3. The biphasic tissue construct according to claim 2 , wherein the bone morphogenetic protein 2 (BMP2) peptide is immobilized on a surface of the scaffold.4. The biphasic tissue construct according to claim 1 , wherein the scaffold comprises biodegradable polylactic acid (PLA) fibers claim 1 , polycaprolactone (PCL) claim 1 , poly(lactic-co-glycolic acid) (PLGA) claim 1 , and any combination thereof.5. The biphasic tissue construct according to claim 4 , wherein the scaffold is coated with polydopamine (pDA).6. The biphasic biomimetic tissue construct according to claim 1 , wherein the scaffold comprises a material having a compression modulus from about 0.03 to about 0 ...

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Номер записи: 20

04-02-2021 дата публикации

CELL PREPARATIONS FOR EXTEMPORANEOUS USE, USEFUL FOR HEALING AND REJUVENATION IN VIVO

Номер: US20210030805A1

Автор: DU TOIT Donald, TURZI ANTOINE

Принадлежит:

The present invention relates to new plasma or new platelet-rich plasma preparations, new cell dissociation methods, new cell associations or compositions, a method of preparation thereof, a use thereof, devices for the preparation thereof and preparations containing such a platelet-rich plasma preparation and cell associations or compositions. Specifically, the invention provides plasma or platelet-rich plasma alone or in cell composition preparations for use in tissue regeneration and bone regeneration and pain reduction. 130-. (canceled)31. A sterilized , vacuum sealed separator tube for preparing a therapeutic platelet concentrate from whole blood comprising:an inlet adapted to introduce whole blood;an anticoagulant composition comprising either: (i) a sodium citrate solution; or (ii) anhydrous sodium citrate; anda thixotropic gel selected from a polyester-based gel or a polymer mixture gel, the thixotropic gel being water insoluble and chemically inert to blood constituents;{'sup': '12', 'wherein the separator tube is adapted to be centrifuged when at least partially filled with the whole blood, at about 1,500 g up to about 2,000 g for about 3 to about 10 minutes in a single centrifugation to separate blood components in the whole blood into at least: (i) the therapeutic platelet concentrate obtained without supernatant removal and containing greater than 300 billion platelets per liter and less than about 0.6×10red blood cells per liter; and (ii) red blood cells.'}32. The separator tube according to claim 31 , wherein the anticoagulant composition comprises a 0.1 M sodium citrate solution.33. The separator tube according to claim 31 , wherein the anticoagulant composition comprises anhydrous sodium citrate.34. The separator tube according to claim 31 , wherein the thixotropic gel is a polyester-based gel.35. The separator tube according to claim 31 , wherein the separator tube is comprised at least of polyethylene terephthalate (PET).36. (canceled)37. ( ...

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Номер записи: 21

04-02-2021 дата публикации

Tissue Engineered Intestine

Номер: US20210030924A1

Автор: Besner Gail E., JOHNSON Jed, Liu Yanchun

Принадлежит:

The invention provides for engineered intestinal construct and methods of making these constructs. The invention also provides for methods of treating short bowel syndrome or methods of repairing an intestine after resection comprising inserting an engineered intestinal construct into the intestine of a subject in need. 1. An engineered intestine construct comprising a nanofiber scaffold seeded with neural stem cells , smooth muscle cells and intestinal stem cells , and wherein the nanofiber scaffold comprises HB-EGF polypeptide or a fragment thereof.2. An engineered intestine construct comprising a nanofiber scaffold seeded with neural stem cells , smooth muscle cells and intestinal stem cells , wherein at least one of the neural stem cells , smooth muscle cells or intestinal stem cells overexpress HB-EGF polypeptide or a fragment thereof.3. An engineered intestine construct comprising a multilayer nanofiber scaffold ,wherein the multilayer nanofiber scaffold comprises at least an inner layer and an outer layer,wherein the outer layer comprises neural stem cells and smooth muscle cells, andwherein the inner layer comprises intestinal stem cells.4. The engineered intestine construct of wherein at least one of the layers comprises HB-EGF polypeptide or a fragment.5. The engineered intestine construct of wherein the construct further comprises at least one middle layer.6. The engineered intestine construct of wherein the nanofiber scaffold comprises Poly(glycolic acid) (PGA) nanofibers claim 1 , Poly(ε-caprolactone) (PCL) nanofibers claim 1 , Poly(-caprolactone-co-lactic acid) (PLC) nanofibers claim 1 , Poly(L-lactic acid) (PLLA) nanofibers claim 1 , Poly(D-lactic acid-co-glycolic acid) (PDLGA) nanofibers claim 1 , Poly(D-lactic acid-co-glycolic acid) (PLGA) nanofibers claim 1 , Polyurethane (PU) nanofibers claim 1 , Polydioxanone (PDO) nanofibers or a combination therefor.7. The engineered intestine construct of wherein the construct comprises a layer of macrofibers ...

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Номер записи: 22

08-02-2018 дата публикации

Cell Preparations For Extemporaneous Use, Useful For Healing And Rejuvenation In Vivo

Номер: US20180036346A1

Автор: DU TOIT DONALD FRANCOIS, TURZI ANTOINE

Принадлежит:

The present invention relates to new plasma or new platelet-rich plasma preparations, new cell dissociation methods, new cell associations or compositions, a method of preparation thereof, a use thereof, devices for the preparation thereof and preparations containing such a platelet-rich plasma preparation and cell associations or compositions. Specifically, the invention provides plasma or platelet-rich plasma alone or in cell composition preparations for use in tissue regeneration and bone regeneration and pain reduction. 1. A method of treating a patient with platelet rich plasma , the method comprising:withdrawing blood from the patient;centrifuging the blood in a centrifugation tube containing a thixotropic gel and an anticoagulant, the thixotropic gel being configured to separate platelet rich plasma, the centrifuging being performed for a length of time such that the thixotropic gel forms a barrier between plasma and erythrocytes;removing the platelet rich plasma from the tube; andadministering the platelet rich plasma to the patient.2. The method of claim 1 , wherein said centrifuging comprises centrifuging the tube at a force between about 1500 g and about 2000 g for about 3 to 10 minutes.3. The method of claim 1 , wherein said centrifuging comprises centrifuging the tube at a force of at least 1500 g for at least 8 minutes.4. The method of claim 1 , further comprising separating the platelet rich plasma by removing approximately half of a supernatant containing platelet poor plasma.5. The method of claim 4 , further comprising re-suspending the platelet rich plasma in the tube claim 4 , wherein said re-suspending follows said separating the platelet rich plasma.6. The method of claim 1 , further comprising admixing the platelet rich plasma with a coagulation activator claim 1 , wherein the coagulation activator comprises at least one of: a thrombin activator claim 1 , a fibrinogen activator claim 1 , a calcium claim 1 , a calcium salt claim 1 , a CaCl ...

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Номер записи: 23

07-02-2019 дата публикации

BONE-LIKE PROSTHETIC IMPLANTS

Номер: US20190038806A1

Автор: MERETZKI Shai

Принадлежит:

A prosthetic implant comprising a biocompatible three-dimensional scaffold and at least two cell types selected from the group consisting of osteoblasts, osteoclasts, and endothelial cells or progenitors thereof. 154-. (canceled)55. A method for repairing a bone lesion in a subject in need thereof , comprising inserting an implant comprising a mineral scaffold carrying cells into said bone lesion , wherein said cells comprise a combination of osteoprogenitor cells and mesenchymal stem cells , thereby repairing a bone lesion in a subject in need thereof.56. The method of claim 55 , wherein said cells further comprise osteoblasts claim 55 , osteoclasts claim 55 , chondrocytes claim 55 , endothelial cells claim 55 , or any combination thereof.57. The method of claim 55 , wherein said cells are at a density of at least 106 cells/ml of said implant.58. The method of claim 55 , wherein said cells are arranged within more than one layer.59. The method of claim 55 , wherein said cells are derived from bone marrow claim 55 , placenta claim 55 , adipose tissue claim 55 , cord blood claim 55 , cord vein claim 55 , peripheral blood claim 55 , mobilized peripheral blood claim 55 , embryonic stem cells claim 55 , or any combination thereof.60. The method of claim 55 , wherein said scaffold has a pore size in the range of from about 50 microns to about 2000 microns.61. The method of claim 55 , wherein said scaffold comprises a bone particle selected from the group consisting of: a dry bone particle claim 55 , a frozen bone particle a dematerialized bone particle claim 55 , or any combination thereof.62. The method of claim 55 , wherein said scaffold comprises: a calcium phosphate derivative claim 55 , a calcium sulfate derivative claim 55 , calcium hydroxyapatite claim 55 , a silicate matrice claim 55 , hydroxyapatite claim 55 , beta-3 calcium phosphate claim 55 , or any combination thereof.63. The method of claim 55 , wherein said implant further comprises poly-D-lysine claim 55 ...

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Номер записи: 24

07-02-2019 дата публикации

TISSUE ENGINEERING

Номер: US20190038807A1

Автор: DECOPPI Paolo, Urbani Luca, URCIUOLO Anna

Принадлежит: UCL Business PLC

The present invention relates generally to methods and materials for use in the production of implants, particularly luminal tissue implants, where the implants are engineered by seeding of an acellular scaffold or matrix with muscle cell precursors and fibroblasts, for example injection seeding using particular ratios of cells. The present invention provides methods for producing tissue engineered constructs for implantation into a subject which can utilise novel seeding processes described herein for improved cell engraftment and differentiation. In addition, the invention describes methods for treating an individual by implantation of the engineered constructs or tissues of the invention. 1. A method of producing a tissue construct suitable for implantation into a subject , the method comprising the steps of:(i) providing an acellular scaffold;(ii) seeding a combination of mesoangioblasts and fibroblast cells into or onto the scaffold; and(iii) culturing the seeded scaffold to produce said construct.2. The method as claimed in wherein the subject is human.3. The method as claimed in wherein said tissue construct is suitable for implantation in a luminal organ such as the oesophagus or bowe claim 1 , or to replace said organl.4. The method as claimed in wherein said tissue construct is an oesophageal construct suitable for a neonate or infant.5. The method as claimed in wherein the ratio of mesoangioblasts:fibroblasts used for seeding is 50:50 to 99:1; 65:35 to 90:10; 70:30 to 90:10; 80:20 to 90:10; or 83:17 to 87:13.6. The method as claimed in wherein ratio is about 85:15.7. The method as claimed in wherein the cells are seeded simultaneously or sequentially within or about 1 claim 1 , 2 claim 1 , 3 claim 1 , 4 claim 1 , 5 claim 1 , 6 claim 1 , 7 claim 1 , 8 claim 1 , 9 claim 1 , 10 claim 1 , 11 claim 1 , 12 claim 1 , 24 claim 1 , 36 or 48 hours of each other.8. (canceled)9. The method as claimed in wherein the cells are delivered in a liquid or gel medium and ...

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Номер записи: 25

15-02-2018 дата публикации

Cell Preparations For Extemporaneous Use, Useful For Healing And Rejuvenation In Vivo

Номер: US20180042964A1

Автор: DU TOIT DONALD FRANCOIS, TURZI ANTOINE

Принадлежит:

The present invention relates to new plasma or new platelet-rich plasma preparations, new cell dissociation methods, new cell associations or compositions, a method of preparation thereof, a use thereof, devices for the preparation thereof and preparations containing such a platelet-rich plasma preparation and cell associations or compositions. Specifically, the invention provides plasma or platelet-rich plasma alone or in cell combinations preparations for use in tissue regeneration and bone regeneration and pain reduction. 1. A medical separator system for preparation of a platelet concentrate , comprising: a thixotropic gel being adapted to separate blood components in whole blood to provide a platelet concentrate containing less than or equal to 1% hematocrit and a pellet containing more than or equal to 99% hematocrit by forming a barrier between plasma and erythrocytes when said tube is centrifuged; and', 'an anticoagulant being adapted to at least reduce coagulation of said whole blood., 'a tube being adapted to be centrifuged for a length of time and containing two additives, wherein said two additives include2. The medical separator system of claim 1 , wherein said thixotropic gel is adapted to separate said blood components in said whole blood to provide said platelet concentrate containing 2 or more times a normal level of platelets and growth factors compared to said whole blood.3. The medical separator system of claim 2 , wherein said thixotropic gel is adapted to separate said blood components in said whole blood to provide said platelet concentrate with platelet recovery of 95%±5%.4. The medical separator system of claim 3 , wherein no other additives are contained in said tube.5. A kit comprising:{'claim-ref': {'@idref': 'CLM-00003', 'claim 3'}, 'a medical separator system of ; and'}an applicator device for applying said platelet concentrate to a patient for medical, therapeutic, or skincare application.6. The medical separator system of claim 3 , ...

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Номер записи: 26

15-02-2018 дата публикации

MESH ENCLOSED TISSUE CONSTRUCTS

Номер: US20180043058A1

Автор: Kheradvar Arash

Принадлежит:

A heart valve leaflet including a thermoplastic polyurethane (TPU) mesh material that has a stiffness that is comparable to a native heart valve leaflet, such that it functionally mimics a native heart valve leaflet. The heart valve leaflets optionally include one to three layers of cells cultured on each side of the mesh material. Also disclosed is a heart valve including the heart valve leaflet and a frame. 1. A heart valve leaflet comprising a thermoplastic polyurethane (TPU) mesh material.2. The heart valve leaflet according to comprising one to three layers of cells cultured on each side of the mesh material.3. The heart valve leaflet according to claim 2 , wherein the one to three layers of cells comprise smooth muscle cells claim 2 , fibroblasts claim 2 , and/or endothelial cell populations.4. The heart valve leaflet according to claim 3 , wherein the smooth muscle cells are vascular smooth muscle cells (VSMC).5. The heart valve leaflet according to claim 2 , wherein the one to three layers of cells cultured on each side of the mesh material comprise a first layer of smooth muscle cells formed directly on the thermoplastic polyurethane mesh claim 2 , a second layer of fibroblast/myofibroblast cells formed on the first layer claim 2 , and a third layer of endothelial cells formed on the second layer.6. The heart valve leaflet according to claim 2 , wherein a first layer of smooth muscle cells and fibroblast/myofibroblast cells are intermixed together and are formed directly on the thermoplastic polyurethane mesh claim 2 , and a second layer of endothelial cells is formed on the first layer.7. The heart valve leaflet of claim 1 , wherein the TPU mesh material comprises an aliphatic polycarbonate-based thermoplastic polyurethane or an aromatic polycarbonate-based thermoplastic polyurethane.8. The heart valve leaflet of claim 1 , wherein the thermoplastic polyurethane (TPU) mesh material has a tensile strength of about 68.9 MPa claim 1 , an elastic modulus of ...

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Номер записи: 27

10-03-2022 дата публикации

PERFUSABLE-TYPE DUAL PROXIMAL TUBULE CELL CONSTRUCT AND PRODUCING METHOD THEREOF FOR APPLYING IN VITRO ARTIFICIALRENAL TISSUE MODEL AND RENAL CELL THERAPY

Номер: US20220072203A1

Автор: Cho Dong-Woo, Han Wonil, Kim Yong Kyun, Nam Sun Ah, Singh Narendra K.

Принадлежит:

The present disclosure is related to a perfusable-type bio-dual proximal tubule cell construct and a producing method thereof capable of applying an in vitro artificial organ model configured to include a first bioink comprising a decellularized substance derived from a mammalian kidney tissue and human umbilical vascular endothelial cells (HUVECs) and a second bioink comprising the decellularized substance and renal proximal tubular epithelial cells (RPTECs), wherein the first bioink and the second bioink are coaxial and printed in tubular constructs having different inner diameters. 1. A perfusable-type bio-dual proximal tubule cell construct capable of applying an in vitro artificial organ model comprising:a first bioink comprising a decellularized substance derived from a mammalian kidney tissue and human umbilical vascular endothelial cells (HUVECs); anda second bioink comprising the decellularized substance and renal proximal tubular epithelial cells (RPTECs),wherein the first bioink and the second bioink are coaxial and printed in tubular constructs having different inner diameters.2. The perfusable-type bio-dual proximal tubule cell construct of claim 1 , wherein the first bioink is printed to configure a first tubular construct claim 1 ,the second bioink is printed to configure a second tubular construct, andat least a part of an outer surface of the first tubular construct is configured to be in contact with an inner surface of the second tubular construct.3. The perfusable-type bio-dual proximal tubule cell construct of claim 2 , wherein the first bioink and the second bioink are configured to include alginate so as to reduce a shape change after printing.4. The perfusable-type bio-dual proximal tubule cell construct of claim 3 , wherein the first bioink and the second bioink are configured to comprise the decellularized substance in a concentration of 20 mg/ml to 40 mg/ml and the alginate in a concentration of 5 mg/ml to 15 mg/ml.5. The perfusable-type ...

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Номер записи: 28

01-03-2018 дата публикации

Tissue Use for Repair of Injury

Номер: US20180055622A1

Автор: Brian DORN, David Shepard, John TOKISH

Принадлежит: Arthrex Inc

The present disclosure describes methods of treating an injury in a subject using placental tissue streamers, engineered tissue placental tissue hybrids, suture placental tissue hybrids, placental tissue patch hybrids, and tissue hybrids, and the use of these compositions to repair, treat, or support an injury or degenerative process in a subject.

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Номер записи: 29

01-03-2018 дата публикации

BIOENGINEERED ALLOGENEIC BLOOD VESSEL

Номер: US20180055973A1

Автор: Olausson Michael, Sumitran-Holgersson Suchitra

Принадлежит:

The present invention relates to methods for recellurization of blood vessels. This method is particularly useful for producing an allogeneic vein, wherein a donor vein is decellularized and then recellularized using whole blood or bone marrow stem cells. The allogeneic veins produced by the methods disclosed herein are particularly advantageous for implantation or transplantation into patients with vascular diseases. 1. A method of recellularizing a blood vessel comprising introducing endothelial cells and smooth muscle cells and/or progenitor cells for endothelial and smooth muscle cells to the lumen of a decellularized blood vessel and culturing said population of cells on the decellularized blood vessel , thereby recellularizing the blood vessel.2. The method of claim 1 , wherein said cells are from peripheral or whole blood or from bone marrow.3. The method of claim 1 , wherein said cells are introduced as whole blood.4. The method of claim 1 , wherein said cells are expanded and differentiated into endothelial cells and smooth muscle cells in vitro prior to introducing the endothelial cells and the smooth muscle cells to the decellularized blood vessel.5. The method of claim 1 , wherein said introducing the cells to the decellularized blood vessel is by injection or perfusion.6. The method of claim 1 , wherein said culturing comprises perfusion of endothelial cell medium and/or smooth muscle cell medium.7. The method of claim 6 , wherein said perfusion of said endothelial cell medium and said smooth muscle cell medium are administered in alternation.8. The method of claim 7 , wherein said administration in alternation is repeated at least twice.9. The method of claim 1 , wherein said culturing the cells on the decellularized blood vessel results in proliferation and/or differentiation of the cells to endothelial cells and smooth muscle cells.10. The method of claim 9 , wherein said endothelial cells line the inner lining or the lumen of the decellularized ...

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Номер записи: 30

28-02-2019 дата публикации

Corneal Implant

Номер: US20190060054A1

Автор: Chandrashekar Balachandran

Принадлежит: Individual

A method for performing a corneal transplantation comprising the steps of: inserting at least part of a corneal implant into the anterior chamber of the eye, the corneal implant comprising an implant portion and a manipulating portion, the manipulating portion comprising non-endothelial tissue; positioning the implant portion of the implant to adhere to the posterior surface of the cornea using the manipulating portion.

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Номер записи: 31

17-03-2022 дата публикации

INFUSED CARTILAGE PARTICLES

Номер: US20220080082A1

Автор: Ganey Timothy

Принадлежит:

A method of making infused non-demineralized cartilage particles employs the following steps: cutting or shaving cartilage tissue into cartilage particles, washing the particles, and infusing the particles with a supernatant of biologic material or a polyampholyte cryoprotectant or a combination of both to create infused particles. 1. A method of making infused non-demineralized cartilage particles comprises:cutting or shaving cartilage tissue into particles;washing the particles; andinfusing the particles with a supernatant of biologic material or a polyampholyte cryoprotectant or a combination of both to create infused particles.2. The method of wherein the step of infusing includes exposing the particles to a negative pressure or vacuum to draw the supernatant and/or the polyampholyte cryoprotectant into the particles.3. The method of wherein the step of infusing includes exposing the particles to a positive pressure to drive the supernatant and/or the polyampholyte cryoprotectant into the particles.4. The method of wherein the particles are ground into an aspherical shape.5. The method of further comprises freezing the supernatant and/or the polyampholyte cryoprotectant infused particles.6. The method of wherein the step of cutting or shaving includes passing the cartilage tissue through a cutting die to form shaped particles.7. The method of wherein the shaped particles have a Non-symmetrical randomness that mirrors the structural intricacy of biological tissues as infinitesimally variable.8. The method of further comprises the step of drying the infused particles.9. The method of wherein the step of drying includes freeze-drying by lyophilization.10. The method of further comprises one or more of the steps of shaping claim 8 , extrusion claim 8 , molding or flattening the dried particles into sheets to form random particle stacked matting.11. An infused composition comprises non-demineralized cartilage particles taken from cartilage and infused with one or ...

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Номер записи: 32

28-02-2019 дата публикации

Engineered Three-Dimensional Connective Tissue Constructs and Methods of Making the Same

Номер: US20190062707A1

Автор: EVINGER, III Albert J., PRESNELL Sharon C., SHEPHERD Benjamin R.

Принадлежит:

Disclosed are engineered, living, three-dimensional connective tissue constructs comprising connective tissue cells. In some embodiments, the connective tissue cells are derived from multi-potent cells such as mesenchymal stem/stromal cells. In some embodiments, the cells are cohered to one another. In some embodiments, the multi-potent cells have been exposed to one or more differentiation signals to provide a living, three-dimensional connective tissue construct. In some embodiments, the constructs are substantially free of pre-formed scaffold at the time of use. Also disclosed are implants for engraftment, arrays of connective tissue constructs for in vitro experimentation, as well as methods of making the same. 156-. (canceled)57. A method of fabricating a living , three-dimensional connective tissue construct comprising:(a) bioprinting a bio-ink comprising multi-potent cells onto a support that is free of pre-formed scaffold;(b) exposing the multi-potent cells to one or more differentiation signals for connective tissue cell differentiation; and(c) incubating the bioprinted bio-ink for about 1 hour to about 30 days, to allow the bio-ink to cohere and to form the living, three-dimensional connective tissue construct.58. The method of claim 57 , wherein the multi-potent cells comprise one or more of: tissue-specific progenitors claim 57 , mesenchymal stem/stromal cells claim 57 , induced pluripotent stem cells claim 57 , and embryonic stem cells.59. The method of claim 57 , wherein the multi-potent cells are derived from mammalian adipose tissue.60. The method of claim 57 , wherein the multi-potent cells are derived from mammalian bone marrow.61. The method of claim 57 , wherein the multi-potent cells are derived from a non-adipose claim 57 , non-bone marrow tissue source.62. The method of claim 57 , wherein the multi-potent cells are exposed to the one or more differentiation signals before the bioprinting claim 57 , during the bioprinting claim 57 , after the ...

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Номер записи: 33

09-03-2017 дата публикации

METHOD FOR GENERATING CELL CONDENSATE FOR SELF-ORGANIZATION

Номер: US20170067014A1

Автор: Takebe Takanori, Taniguchi Hideki, Yoshikawa Hiroshi

Принадлежит:

The present invention finds out find out the requirements necessary for preparing a cell condensate in vitro from a large number of cells (several ten thousand to several million cells) and provides a method of forming a cell condensate for self-organization which is capable of realizing complex higher structures (such as liver and kidney) and interactions with other organs. 1. A method of preparing a cell condensate in vitro , comprising culturing a mixture of cells and/or tissues of a desired type and mesenchymal cells to form a cell condensate.2. The method of claim 1 , wherein the cell condensate is capable of forming a three-dimensional tissue structure that has been provided with higher structures by self-organization.3. The method of claim 1 , wherein the mixture of cells and/or tissues of a desired type and mesenchymal cells is cultured on a gel-like support on which the mesenchymal cell is capable of contraction.4. The method of claim 3 , wherein the culture is two-dimensional culture.5. The method of claim 3 , wherein the gel-like support is planar or the side of the gel-like support on which culture is performed has a U- or V-shaped cross-section.6. The method of claim 3 , wherein the stiffness of the central part of the gel-like support is greater than the stiffness of the peripheral part thereof.7. The method of claim 3 , wherein the stiffness of the peripheral part of the gel-like support is greater than the stiffness of the central part thereof.8. The method of claim 3 , wherein the gel-like support is patterned and has one or more patterns in which the stiffness of the central part is greater than the stiffness of the peripheral part.9. The method of claim 3 , wherein the gel-like support is patterned and has one or more patterns in which the stiffness of the peripheral part is greater than the stiffness of the central part.10. The method of claim 1 , wherein the total cell count of the cells and/or tissues of a desired type has a total cell count of ...

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Номер записи: 34

15-03-2018 дата публикации

ANGIOGENESIS USING PLACENTAL STEM CELLS

Номер: US20180071343A1

Автор: Abbot Stewart, EDINGER James, Francki Aleksander, Hariri Robert J., JANKOVIC Vladimir, Kaplunovsky Aleksandr, Labazzo Kristen, LAW Eric, Padliya Neerav, Paredes Jennifer, Wang Jia-Lun

Принадлежит: CELULARITY, INC.

Provided herein are methods of treating individuals having diseases or disorders of the circulatory system, using placental cells, e.g., the placental stem cells and placental multipotent cells (PDACs) described herein, and populations of such placental cells. The invention also provides methods of angiogenesis using such cells or populations of cells comprising such cells. 1. An isolated placental derived adherent cell , wherein said cell is adherent to tissue culture plastic , and wherein said cell is CD10 , CD34 , CD105 and CD200 as determined by flow cytometry , and wherein said cell (1) promotes the proliferation of endothelial cells; (2) promotes the formation of sprouts or tube-like structures in a population of endothelial cells; or (3) promote the migration of endothelial cells.2. The isolated cell of claim 1 , wherein said cell is CD45 and CD90 claim 1 , as determined by flow cytometry.3. The isolated cell of claim 1 , wherein said cells express one or more of VEGF claim 1 , HGF claim 1 , IL-8 claim 1 , MCP-3 claim 1 , FGF2 claim 1 , follistatin claim 1 , G-CSF claim 1 , EGF claim 1 , ENA-78 claim 1 , GRO claim 1 , IL-6 claim 1 , MCP-1 claim 1 , PDGF-BB claim 1 , TIMP-2 claim 1 , uPAR claim 1 , or galectin-1 as determined by antibody binding.4. An isolated population of cells comprising the cell of .5. The isolated population of cells of claim 1 , wherein at least 50% of the cells in said population are the cells of .6. The isolated population of cells of claim 1 , wherein at least 90% of the cells in said population are the cells of .7. The isolated population of cells of claim 1 , wherein at least 50% of the cells in said population are the cells of .8. The isolated population of cells of claim 1 , wherein at least 90% of the cells in said population are the cells of .9. A composition comprising the isolated placental derived adherent cell of .10. The isolated population of comprising a second type of cell.11. The isolated population of cells of claim 10 ...

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Номер записи: 35

16-03-2017 дата публикации

Bioengineered Allogeneic Valve

Номер: US20170071738A1

Автор: Hisdal Jonny, Rosales Antonio, Sumitran-Holgersson Suchitra

Принадлежит:

The present disclosure relates to methods for recellularization of valves in valve-bearing veins. This method is useful for producing an allogeneic venous valve, wherein a donor valve-bearing vein is decellularized and then recelluiarized using whole blood or bone marrow stem cells. The allogeneic valves produced by the methods disclosed herein are advantageous for implantation, transplantation, or grafting into patients with vascular diseases. 1. A method of recellularization of a valve in a vein , comprising introducing blood comprising progenitor cells for endothelial cells and progenitor cells for smooth muscle cells to the lumen of a decellularized vein , and culturing the cells in the lumen of the decellularized vein , thereby recellularizing the valve in the vein.2. The method of claim 1 , wherein the blood is peripheral venous blood or whole blood.3. The method of claim 2 , wherein the peripheral venous blood or the whole blood is introduced to the decellularized vein by injection or perfusion.4. The method of claim 3 , further comprising culturing the cells by perfusion of endothelial cell medium and smooth muscle cell medium.5. The method of claim 4 , wherein the perfusion of the endothelial cell medium and the smooth muscle cell medium are in alternation.6. The method of one of the above claims claim 4 , wherein the recellularized valve is CD31 positive claim 4 , vWF positive claim 4 , smooth muscle actin positive claim 4 , and has nuclei.7. The method of one of the above claims claim 4 , wherein the recellularized valve has mechanical properties of withstanding force at first peak at or above 0.8 N.8. The method of one of the above claims claim 4 , wherein the recellularized valve has a closure time of equal to or less than 0.5 seconds.9. A method of treating chronic venous insufficiency (CVI) claim 4 , deep vein thrombosis (DVT) claim 4 , and/or leg ulceration in a subject in need thereof claim 4 , comprising introducing a recellularized valve-bearing ...

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Номер записи: 36

07-03-2019 дата публикации

ELECTRO-MECHANICALLY STRETCHED MICRO FIBERS AND METHODS OF USE THEREOF

Номер: US20190070339A1

Автор: Barreto Ortiz Sebastian F., Gerecht Sharon, Mao Hai-Quan, Zhang Shuming

Принадлежит:

The presently disclosed subject matter provides a scalable and electrostretching approach for generating hydrogel microfibers exhibiting uniaxial alignment from aqueous polymer solutions. Such hydrogel microfibers can be generated from a variety of water-soluble natural polymers or synthetic polymers. The hydrogel microfibers can be used for controlled release of bioactive agents. The internal uniaxial alignment exhibited by the presently disclosed hydrogel fibers provides improved mechanical properties to hydrogel microfibers, and contact guidance cues and induces alignment for cells seeded on or within the hydrogel microfibers. 1. A biodegradable microfiber having a longitudinally aligned nanotopography comprising biodegradable , electrostretched , hydrogel , polymer nanofibers with internal polymer alignment.2. The microfiber of wherein the nanofibers are parallel to each other.3. The microfiber of wherein the nanofibers are substantially free of a ceramic.4. The microfiber of wherein the nanofibers form a conduit with a diameter in the range of 20 micrometers to 20 mm.5. The microfiber of comprising a solid bundle of nanofibers with a diameter of 0.1 to 100 nm.6. The microfiber of claim 1 , wherein the hydrogel polymer nanofibers has a water content of greater than about 90%.7. The microfiber of having a diameter from about 100 μm to about 500 μm based on the outer circumference of the microfiber.8. The microfiber of claim 1 , wherein the polymer is selected from the group consisting of alginate claim 1 , fibrin (fibrinogen) claim 1 , gelatin claim 1 , hyaluronic acid claim 1 , and a combination thereof.9. The microfiber of claim 8 , wherein the polymer is fibrin.10. The microfiber of claim 1 , further comprising endothelial progenitor cells seeded on the polymer microfiber.11. The microfiber of claim 10 , wherein the endothelial progenitor cells are endothelial colony forming cells.12. The microfiber of claim 11 , wherein the endothelial colony forming cells ...

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Номер записи: 37

19-03-2015 дата публикации

Mesh enclosed tissue constructs

Номер: US20150081012A1

Автор: Arash Kheradvar, Seyedhamed Alavi

Принадлежит: UNIVERSITY OF CALIFORNIA

A scaffold to form tissue membranes, comprising: at least one layer of mesh having a first side and a second side, the layer of mesh being either a woven wire metal mesh or a flat metal sheet that is acid-etched such that the layer of mesh includes a network of holes passing directly through the mesh from the first side to the second side; and at least one layer of cells at each side of the mesh enclosing the layer of mesh, such that the at least one layer of cells on the first side interacts with the at least one layer of cells on the second side through the network of holes to provide for structure integration.

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Номер записи: 38

23-03-2017 дата публикации

Cell Preparations For Extemporaneous Use, Useful for Healing and Rejuvenation In Vivo

Номер: US20170080028A1

Автор: DU TOIT DONALD FRANCOIS, TURZI ANTOINE

Принадлежит:

The present invention relates to new plasma or new platelet-rich plasma preparations, new cell dissociation methods, new cell associations or compositions, a method of preparation thereof, a use thereof, devices for the preparation thereof and preparations containing such a platelet-rich plasma preparation and cell associations or compositions. Specifically, the invention provides plasma or platelet-rich plasma alone or in cell combinations preparations for use in tissue regeneration and bone regeneration and pain reduction. 1. A separator system for the preparation of a platelet rich plasma , comprising:a tube;a thixotropic gel disposed in the tube, the thixotropic gel being adapted for separating platelet rich plasma and including a polymer mixture; andan anticoagulant disposed in the tube, the anticoagulant including a buffered sodium citrate solution at 0.1 M;the tube being adapted to be centrifuged for a sufficient length of time to form a barrier with the thixotropic gel between plasma and erythrocytes.2. A platelet rich plasma produced by centrifuging whole blood in the separator system of .3. The platelet rich plasma of claim 2 , wherein centrifugation is performed at a force between about 1000 g and about 2000 g.4. The platelet rich plasma of claim 2 , wherein a cell extract is mixed with the platelet rich plasma.5. A method of treating a patient with platelet rich plasma claim 2 , comprising:withdrawing blood from the patient;centrifuging the blood in a glass tube containing a thixotropic gel and an anticoagulant, the centrifuging being performed for a sufficient length of time to form a barrier between plasma and erythrocytes;removing the platelet rich plasma from the tube; andadministering the platelet rich plasma to the patient.6. The method of claim 5 , wherein the treating comprises tissue healing or regeneration treatments claim 5 , traumatic or surgical wound treatments claim 5 , vasculitis treatments claim 5 , ulcer or decubitus sore treatments ...

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Номер записи: 39

12-03-2020 дата публикации

SYNTHETIC HYDROGEL CARRIERS FOR CELLULAR STRUCTURES, GENERATION OF ORGANOIDS, AND TREATMENT OF TISSUE INJURY

Номер: US20200078493A1

Автор: CRUZ-ACUNA Ricardo, Garcia Andres J., Nusrat Asma, QUIROS Miguel, Spence Jason R.

Принадлежит:

Disclosed herein are synthetic hydrogel useful for the generation, storage and administration of cellular structures such as spheroids and organoids. 1. A composition comprising a cellular structure dispersed in a hydrogel matrix , wherein the hydrogel matrix comprises a crosslinked hydrophilic polymer network covalently bonded to a plurality of adhesion peptides.2. The composition according to claim 1 , wherein the cellular structure comprises an organoid claim 1 , cellular spheroid claim 1 , stem cell claim 1 , or combination thereof.3. The composition of claim 2 , wherein the cellular structure comprises an organoid comprising an intestinal organoid claim 2 , gastric organoid claim 2 , or lingual organoid.46-. (canceled)7. The composition according to claim 2 , wherein the cellular structure comprises a stem cell comprising multipotent stem cells claim 2 , totipotent stem cells claim 2 , pluripotent stem cells claim 2 , embryonic stem cell claim 2 , induced pluripotent stem cells claim 2 , extraembryonic fetal stem cells claim 2 , amniotic stem cells claim 2 , or adult stem cells.98. The composition according claim 2 , wherein the hydrophilic polymer comprises a multi-armed poly(ethylene glycol).13. The composition according to claim 1 , wherein the adhesion peptide comprises the amino acid sequence RGD.14. (canceled)15. The composition according to claim 13 , wherein the adhesion peptide comprises the amino acid sequence GRGDSPC16. The composition according to claim 1 , wherein the crosslinked hydrophilic polymer is crosslinked with a crosslinker comprising a MMP- or cathepsin- or other protease-cleavable or non-cleavable peptide comprising at least a cysteine residue at each end of the sequence.17. (canceled)18. The composition according to claim 1 , wherein the crosslinker comprises 1 claim 1 ,4-dithiothreitol poly(ethylene glycol) dithiol.19. The composition according to claim 1 , wherein the crosslinked hydrophilic polymer network is present claim 1 , on a ...

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Номер записи: 40

12-03-2020 дата публикации

COMPOSITIONS AND METHODS FOR BIOENGINEERED TISSUES

Номер: US20200080061A1

Автор: Dinh Timothy Anh-Hieu, Hanson Arial Dawn, Reid Lola M., Sethupathy Praveen, Wauthier Eliane Lucie, YAMAUCHI Mitsuo

Принадлежит: The University of North Carolina at Chapel Hill

The present disclosure provides methods for producing bioengineered tissue along with an apparatus and other relevant compositions employed in generation thereof. 127.-. (canceled)28. A bioengineered tissue generated by introducing epithelial and mesenchymal cells into or onto a biomatrix scaffold , wherein the biomatrix scaffold comprises collagens , and wherein the epithelial and mesenchymal cells are maturational lineage partners.29. The bioengineered tissue of claim 28 , in which the epithelial and mesenchymal cells are in a seeding medium claim 28 , and the seeding medium is replaced with a differentiation medium after an initial incubation period.30. The bioengineered tissue of claim 29 , in which the differentiation medium comprises:a) a basal medium;b) lipids, insulin, transferrin, antioxidants;c) copper;d) calcium;e) one or more signaling molecules for the propagation or maintenance of epithelial cells; and/orf) one or more signaling molecules for the propagation or maintenance of mesenchymal cells.31. The bioengineered tissue of claim 29 , in which the seeding medium is serum-free or is supplemented with between about 2% to 10% fetal serum.32. The bioengineered tissue of claim 29 , in which the seeding medium comprises:a) a basal medium;b) lipids;c) insulin;d) transferrin; and/ore) antioxidants.33. The bioengineered tissue of claim 29 , in which the epithelial and mesenchymal cells in the seeding medium is incubated at 4° C. in the seeding medium for 4 to 6 hours prior to introduction into the biomatrix scaffold.34. The bioengineered tissue of claim 28 , in which the biomatrix scaffold is three-dimensional.35. The bioengineered tissue of claim 28 , in which the collagens in the biomatrix scaffold comprises (i) nascent collagens claim 28 , (ii) aggregated but not cross-linked collagen molecules claim 28 , and/or (iii) cross-linked collagens.36. The bioengineered tissue of claim 29 , in which the epithelial and mesenchymal cells in the seeding medium are ...

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Номер записи: 41

30-03-2017 дата публикации

BIOERODIBLE MATRIX FOR TISSUE INVOLVEMENT

Номер: US20170087273A1

Автор: Powell Thomas E., Van Epps Dennis E.

Принадлежит:

Disclosed herein are polyurethane polymer matrices with a porosity of from about 20 microns to about 90 microns that are useful in promoting closure and protection of incision sites; supporting the lower pole position of breast implants; and providing a partial or complete covering of breast implants to provide a beneficial interface with host tissue and to reduce the potential for malpositioning or capsular contracture. The disclosed matrices can be seeded with mammalian cells. 1. A medical implant comprising:a breast prosthesis; anda matrix on said breast prosthesis, the matrix comprising a resorbable or bioerodible polymer component and a cellular component, the matrix having a porosity conducive to cell growth and capable of providing a beneficial interface between the prosthesis and host tissue and reducing the potential for malpositioning or capsular contracture.2. The implant of wherein the polymer component comprises a polyurethane polymer.3. The implant of wherein the polymer component comprises polycarolactone soft segments.4. The implant of wherein the cellular component comprises stem cells.5. The implant of wherein the cellular component comprises adipose cells.6. The implant of wherein the cellular component comprises stem cells and adipose cells.7. The implant of wherein the matrix forms at least a partial covering on said breast prosthesis.8. The implant of wherein the matrix forms a complete covering of said breast prosthesis.9. The implant of wherein the matrix has a pore size diameter of o about 10 to about 1000 microns.10. The implant of wherein the matrix has a pore size diameter of from about 20 to about 90 microns. This application is a continuation of U.S. patent application Ser. No. 14/189,457 filed on Feb. 25, 2014, which is a continuation of Ser. No. 13/453,886, filed on Apr. 23, 2012, now abandoned, which is a divisional of U.S. patent application Ser. No. 12/705,177, filed on Feb/ 10, 2010, now abandoned, which claims priority to U.S. ...

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Номер записи: 42

30-03-2017 дата публикации

Compositions and Methods for Tissue Repair with Extracellular Matrices

Номер: US20170087275A1

Автор: Christman Karen, DeQuach Jessica

Принадлежит:

Described herein are compositions comprising decellularized extracellular matrix derived from skeletal muscle or other suitable tissue, and therapeutic uses thereof. Methods for treating, repairing or regenerating defective, diseased, damage, ischemic, ulcer cells, tissues or organs in a subject preferably a human, with diseases, such as PAD and CLI, using a decellularized extracellular matrix of the invention are provided. Methods of preparing culture surfaces and culturing cells with absorbed decellularized extracellular matrix are provided. 1. A method for treating peripheral artery disease or critical limb ischemia comprising:injecting or implanting in a subject with peripheral artery disease or critical limb ischemia a therapeutically effective amount of a composition comprising decellularized extracellular matrix derived from a suitable tissue.2. The method of claim 1 , wherein the suitable tissue is selected from the group consisting of cardiac claim 1 , pericardial claim 1 , liver claim 1 , brain claim 1 , small intestine submucosa claim 1 , bladder claim 1 , lung claim 1 , and vascular tissue.3. The method of claim 1 , wherein the therapeutically effective amount is an amount that increases blood flow claim 1 , increases muscle mass claim 1 , or induces new vascular formation in an area of composition injection or implantation.4. The method of claim 1 , wherein the composition is coated on an implant.5. The method of claim 1 , wherein the composition is delivered as a liquid or a powder.6. The method of claim 5 , wherein the composition transitions to a gel form after delivery.7. The method of claim 1 , wherein the composition degrades within one to three months following injection or implantation.8. The method of claim 1 , wherein damaged skeletal muscle tissue is repaired following injection or implantation of the composition.9. The method of claim 1 , wherein the therapeutically effective amount is an amount effective to treat at least one peripheral ...

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Номер записи: 43

19-03-2020 дата публикации

METHOD FOR DECELLULARIZATION OF SKIN TISSUE, METHOD FOR CONSTRUCTION OF ARTIFICIAL SKIN, METHOD FOR PREPARATION OF HYDROGEL OF DECELLULARIZED SKIN TISSUE, LYOPHILIZED, DECELLULARIZED SKIN TISSUE, AND BIOINK

Номер: US20200086003A1

Автор: CHO Dong Woo, KIM Byoung Soo, KONG Jeong Sik

Принадлежит:

A method for decellularization of a skin tissue according to an embodiment of the present invention comprises: a step of preparing a skin tissue to be decellularized; a peeling preparation step of treating the skin tissue with a first solution containing trypsin; and a peeling step of removing subcutaneous fat from the skin tissue after the peeling preparation step. 1. A bioink in which normal human dermal fibroblasts (NHDF) are mixed with a decellularized skin tissue by a method for decellularization of a skin tissue , which comprises the steps of:a step of preparing a skin tissue to be decellularized;a peeling preparation step of treating the skin tissue with a first solution containing trypsin; anda peeling step of removing subcutaneous fat from the skin tissue after the peeling preparation step;a cell removal step in which the skin tissue, after undergoing the peeling step, is treated using a buffer solution that comprises ethylenediaminetetraacetic acid (EDTA) and a non-ionic surfactant;a primary washing step in which the skin tissue, which has undergone the cell removal step, is washed;a DNA treatment step in which the skin tissue, which has undergone the primary washing step, is treated using a second solution that comprises magnesium ions and DNase;a secondary washing step in which the skin tissue, which has undergone the DNA treatment step, is washed;a disinfection step in which the skin tissue, which has undergone the secondary washing step, is disinfected using a disinfection solution; anda tertiary washing step in which the disinfected skin is washed.2. The bioink of claim 1 , wherein the first solution further comprises ethylenediaminetetraacetic acid (EDTA).3. The bioink of claim 1 , wherein claim 1 , in the first solution claim 1 , 1 mM or less of the ethylenediaminetetraacetic acid (EDTA) is dissolved and 0.25% or less of the trypsin is dissolved.4. The bioink of claim 1 , wherein the epidermis of the skin tissue is removed in at least one step of ...

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Номер записи: 44

07-04-2016 дата публикации

BONE REGENERATION USING STROMAL VASCULAR FRACTION, PLATELET-DERIVED GROWTH FACTOR-RICH HYDROGEL, THREE-DIMENSIONAL PRINTED POLY-EPSILON-CAPROLACTONE SCAFFOLDS

Номер: US20160095958A1

Автор: COOK COLIN, Grayson Warren, HUNG BEN P.J., Huri Pinar, HUTTON DAPHNE L., TEMPLE JOSHUA

Принадлежит: THE JOHNS HOPKINS UNIVERSITY

The presently disclosed subject matter focuses on recapitulating the heterotypic interactions needed to maximize the co-development of vasculature and bone. More particularly, the presently disclosed subject matter explores the potential of cellular aggregation and temporal presentation of factors to induce the cell-cell signaling events required to stimulate ASCs to self-organize into vascularized bone. Further, exogenous PDGF-BB synergizes complex tissue formation in ASC cultures by enhancing vascular stability and osteogenic differentiation. The presently disclosed approach provides a robust protocol to engineer vascularized bone with ASCs in vitro. 1. A biodegradable scaffold for regenerating bone tissue , the scaffold configured to form a porous , three-dimensional (3D) network of interconnected void spaces , wherein the porous , three-dimensional network further comprises a hydrogel , and wherein the hydrogel comprises one or more cells encapsulated therein and one or more growth factors capable of promoting regeneration of bone tissue.2. The scaffold of claim 1 , wherein the scaffold comprises a biodegradable polymer selected from the group consisting of poly-ε-caprolactone (PCL) claim 1 , poly-lactic acid (PLA) claim 1 , poly-glycolic acid (PGA) claim 1 , and poly-lactic-co-glycolic acid (PLGA).3. The scaffold of claim 2 , wherein the biodegradable polymer comprises poly-ε-caprolactone (PCL).4. The scaffold of claim 1 , wherein the hydrogel comprises a natural polymer selected from the group consisting of fibrinogen claim 1 , alginate claim 1 , gelatin claim 1 , collagen claim 1 , hyaluronic acid (HA) claim 1 , chitosan claim 1 , chondroitin sulfate claim 1 , dextran sulfate claim 1 , heparin claim 1 , heparan sulfate claim 1 , matrigel claim 1 , and laminin.5. The scaffold of claim 4 , wherein the hydrogel comprises fibrinogen.6. The scaffold of claim 1 , wherein the one or more cells comprise autologous cells from bone marrow or adipose tissue.7. The ...

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Номер записи: 45

12-05-2022 дата публикации

Liver Tissue Model Constructs and Methods for Providing the Same

Номер: US20220145259A1

Автор: Gatenholm Erik, Martinez Hector, Namro Redwan Adel Itedal, Nguyen Duong

Принадлежит:

The present invention provides for a liver tissue model construct composed of biomaterials and cells, to be used for scientific research within in the 3D liver tissue modelling field. The applications of said tissue model construct can be specific for pharmaceutical evaluations and/or discoveries, regenerative medicine investigations, tissue engineering developments, and liver physiology and/or pathology. 1. A liver tissue model construct comprising at least one bioprinted structure , wherein the structure comprises a Bioink A mixed with at least one Cell A , and a Bioink B mixed with at least one Cell B ,wherein at least one of Bioink A and Bioink B, independently of each other, is based on methacrylated gelatin, collagen, nanocellulose and/or alginate;wherein at least one of Bioink A and Bioink B comprises liver-specific ECM components;optionally wherein at least one of Bioink A or Bioink B comprises a thickening agent, wherein the thickening agent is a natural polysaccharide selected from the group consisting of: xanthan gum, glucomannan and nanocellulose;wherein at least one of Bioink A or Bioink B comprises a Factor A;wherein Cell A is a hepatic cell line of human or animal origin; andwherein Cell B is a non-parenchymal cell of human or animal origin from cell lines, primary cells, or derived from induced pluripotent stem cells (iPSCs) or embryonic stem cells (ESCs), wherein the non-parenchymal cells are selected from the group consisting of: liver sinusoidal endothelial cells, Kupffer cells, biliary cells, lymphocytes, and hepatic stellate cells in normal and abnormal physiology.2. The liver tissue model construct according to claim 1 , wherein the Bioink A comprises methacrylated gelatin or collagen with a liver specific ECM component.3. The liver tissue model construct according to claim 1 , wherein Bioink B comprises liver specific components.46.-. (canceled)7. The liver tissue model construct according to claim 1 , wherein the Factor A is selected from the ...

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Номер записи: 46

13-04-2017 дата публикации

CULTURED CELL LEAFLET MATERIAL

Номер: US20170100237A1

Автор: Anderson-Cunanan Crystal Marie, EPPIHIMER MICHAEL, Fazackerley Katherine Cora, KENWOOD SHANNON SMITH, Lavery Karen Suzanne, Sushkova Natalia P.

Принадлежит:

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 ...

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Номер записи: 47

02-04-2020 дата публикации

BIOMATERIALS FOR ENHANCED IMPLANT-HOST INTEGRATION

Номер: US20200101201A1

Автор: Baranski Jan D., Bhatia Sangeeta, Chaturvedi Ritika, Chen Christopher S., Stevens Kelly, YANG Michael T.

Принадлежит:

The present disclosure provides patterned biomaterials having organized cords and extracellular matrix embedded in a 3D scaffold. According, the present disclosure provides compositions and applications for patterned biomaterials. Pre-patterning of these biomaterials can lead to enhanced integration of these materials into host organisms, providing a strategy for enhancing the viability of engineered tissues by promoting vascularization. 123-. (canceled)24. A patterned biomaterial comprising: at least one cord , formed by embedding cells in a naturally-derived or synthetic scaffolding with a pre-specified architecture and spatially organizing the cells within the scaffolding , wherein the at least one cord comprises endothelial cells.25. The patterned biomaterial of claim 24 , wherein the patterned biomaterial is configured to promote the vascularization of the patterned biomaterial and a tissue of the subject in which the patterned biomaterial is implanted into claim 24 , wherein the structure of the patterned biomaterial has a pre-specified architecture that acts as a template and spatial guidance for the subject's vasculature claim 24 , such that the subject's vasculature invades and integrates at least partially within the at least one cord.26. The patterned biomaterial of claim 24 , further comprising an extracellular matrix or a physically solid scaffold at least partially encapsulating the at least one cord.27. The patterned biomaterial of claim 26 , wherein the extracellular matrix scaffold comprises fibrin.28. The patterned biomaterial of claim 26 , wherein the extracellular matrix scaffold further comprises at least one cell type.29. The patterned biomaterial of claim 28 , wherein the at least one cell type comprises hepatocytes claim 28 , endothelial cells claim 28 , mesenchymal stem cells claim 28 , or a combination thereof.30. The patterned biomaterial of claim 28 , wherein the at least one cell type comprises endothelial cells.31. The patterned ...

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Номер записи: 48

11-04-2019 дата публикации

CUSTOMIZED HYBRID BONE-IMPLANT GRAFTS

Номер: US20190105429A1

Автор: De Peppo Giuseppe Maria, Sladkova Martina

Принадлежит:

The present invention provides customized hybrid bone-implant grafts and a method of manufacture thereof. 1. A hybrid bone-implant graft comprising:a) an implant material; andb) an engineered bone tissue graft having a scaffold, wherein the graft is composed of cells seeded on the scaffold and cultured to promote attachment of the cells to the implant material.2. The graft of claim 1 , wherein the implant material comprises titanium or steel.3. The graft of claim 1 , wherein the tissue graft comprises cells derived from stem cells or progenitor cells.4. The graft of claim 1 , wherein the tissue graft comprises cells derived from induced pluripotent stem cells.5. The graft of claim 1 , wherein the scaffold has a thickness of from about 0.3 millimeters to about 10 millimeters.6. The graft of claim 1 , wherein the scaffold has a thickness of less than one centimeter.7. The graft of claim 1 , wherein the scaffold consists essentially of decellularized bone tissue.8. The graft of claim 7 , wherein the bone tissue is bovine bone tissue.9. The graft of claim 7 , wherein the bone tissue is human bone tissue.10. The graft of claim 1 , wherein the scaffold comprises one or more synthetic materials.11. The graft of claim 10 , wherein the synthetic material comprises ceramic claim 10 , cement claim 10 , polymer composite claim 10 , or any combination thereof.12. The graft of claim 1 , wherein the scaffold has been functionalized.13. The graft of claim 1 , wherein the scaffold comprises one or more openings to accommodate the implant material.14. The graft of claim 1 , wherein the culturing is carried out under static conditions.15. The graft of claim 1 , wherein the culturing is carried out under dynamic conditions.16. The graft of claim 1 , wherein the culturing is carried out for about 2 claim 1 , about 3 claim 1 , about 4 claim 1 , about 5 claim 1 , about 6 claim 1 , about 7 claim 1 , about 8 claim 1 , about 9 claim 1 , or about 10 weeks.17. The graft of claim 1 , wherein ...

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Номер записи: 49

26-04-2018 дата публикации

SKIN RECONSTRUCTION METHOD

Номер: US20180112188A1

Автор: CARIO-ANDRÉ Muriel, CASOLI Vincent, LEPIVERT Jean-Christophe

Принадлежит:

Some embodiments are directed to a method for preparing a skin substitute, a dermal substitute, to a skin substitute, to a dermal substitute and to a kit for implementing the method. Some other embodiments are directed to a graft that can consist of of a skin substitute and to the use thereof as treating a skin disorder and/or a loss of skin substance. 1. A method for preparing a skin substitute , comprising the steps of:a. culturing of fibroblasts in a fibroblast culture medium M1;b. seeding of a matrix including collagen with fibroblasts resulting from step a;c. culturing of fibroblasts seeded in the matrix including collagen in a fibroblast culture medium M2 including ascorbic acid or an ascorbate or a derivative thereof, the matrix and the cultured fibroblasts forming a dermal substitute;d. culturing of melanocytes in a melanocyte culture medium M3;e. culturing of keratinocytes in a keratinocyte culture medium M4;f. mixing of melanocytes obtained in step d with keratinocytes obtained in step e;g. seeding of the dermal substitute obtained in step c with the mixture obtained in step f;h. culturing of the dermal substitute seeded in step g in a skin culture medium M5 thus forming the skin substitute.2. The method as claimed in claim 1 , wherein the medium M5 includes hyaluronic acid or a hyaluronate or a derivative thereof.3. The method as claimed in claim 2 , wherein the medium M5 includes ascorbic acid or an ascorbate or a derivative thereof.4. The method as claimed in claim 1 , wherein the mixing of melanocytes and keratinocytes of step f is carried out with a melanocytes/keratinocytes ratio of 1/20 to 1/15.5. The method as claimed in claim 1 , wherein the seeding in step g is carried out with a (keratinocytes+melanocytes)/fibroblasts ratio of 9 to 19.6. The method as claimed in claim 1 , wherein the seeding in step b is carried out at a density of from 20 000 to 50 000 fibroblasts/cm2 of surface area of the matrix including collagen.7. The method as claimed in ...

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Номер записи: 50

13-05-2021 дата публикации

TISSUE-ENGINEERED GUT-SPHINCTER COMPLEXES AND METHODS OF MAKING THE SAME

Номер: US20210137668A1

Автор: BITAR Khalil

Принадлежит:

Methods are disclosed for forming tissue engineered, tubular gut-sphincter complexes from intestinal circular smooth muscle cells, sphincteric smooth muscle cells and enteric neural progenitor cells. The intestinal smooth muscle cells and neural progenitor cells can be seeded on a mold with a surface texture that induces longitudinal alignment of the intestinal smooth muscle cells and co-cultured until an innervated aligned smooth muscle sheet is obtained. The innervated smooth muscle sheet can then be wrapped around a tubular scaffold to form an intestinal tissue construct. Additionally, the sphincteric smooth muscle cells and additional enteric neural progenitor cells can be mixed in a biocompatiable gel solution, and the gel and admixed cells applied to a mold having a central post such that the sphinteric smooth muscle and neural progenitor cells can be cultured to form an innervated sphincter construct around the mold post. This innervated sphincter construct can also be transferred to the tubular scaffold such that the intestinal tissue construct and sphincter construct contact each other, and the resulting combined sphincter and intestinal tissue constructs can be further cultured about the scaffold until a unified tubular gut-sphincter complex is obtained. 1. A method of forming a tissue engineered , tubular gut-sphincter complex comprising:isolating intestinal circular smooth muscle cells from an intestinal donor source,isolating sphincteric smooth muscle cells from a sphincteric donor source,isolating enteric neural progenitor cells from at least one neural progenitor donor source,seeding the isolated intestinal circular smooth muscle cells on a mold with a surface texture that induces longitudinal alignment of the intestinal circular smooth muscle cells,adding the isolated enteric neural progenitor cells to the intestinal circular smooth muscle cells on the mold,co-culturing the intestinal circular smooth muscle cells and the enteric neural progenitor ...

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Номер записи: 51

07-05-2015 дата публикации

BIOMATERIALS FOR ENHANCED IMPLANT-HOST INTEGRATION

Номер: US20150125507A1

Автор: Baranski Jan D., Chaturvedi Ritika, Chen Christopher S., YANG Michael T.

Принадлежит: THE TRUSTEES OF THE UNIVERSITY OF PENNSYLVANIA

The present disclosure provides patterned biomaterials having organized cords and extracellular matrix embedded in a 3D scaffold. According, the present disclosure is provides compositions and applications for patterned biomaterials. Pre-patterning of these biomaterials can lead to enhanced integration of these materials into host organisms, providing a strategy for enhancing the viability of engineered tissues by promoting vascularization. 1. A patterned biomaterial comprising: (a) at least one cord, wherein the cord is at least partially embedded in the scaffold in a spatially delineated form and is comprised of at least one cell type; or', '(b) at least one cluster of cells, wherein the cluster of cells is at least partially embedded in the scaffold in a spatially delineated form and is comprised of at least one cell type., 'a naturally-derived or synthetic scaffolding; and'}2. The biomaterial of claim 1 , further comprising an extracellular matrix scaffold encapsulating the at least one cord or the at least one cluster of cells embedded in the naturally-derived or synthetic scaffolding.3. The biomaterial of claim 1 , wherein the naturally-derived or synthetic scaffolding comprises collagen.4. The biomaterial of claim 2 , wherein the extracellular matrix scaffold comprises fibrin.5. The biomaterial of claim 2 , wherein the extracellular matrix scaffold further comprises one or more cell types.6. The biomaterial of claim 5 , wherein the one or more cell types comprises one or more cell types selected from the group consisting of: hepatocytes; endothelial cells; and mesenchymal stem cells.7. The biomaterial of claim 1 , wherein the at least one cord is branched.8. A system comprising:an engineered tissue; anda patterned biomaterial comprising a naturally-derived or synthetic scaffolding and at least two cords, wherein the cords are at least partially embedded in the naturally-derived or synthetic scaffolding in a spatially delineated form and are comprised of one ...

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Номер записи: 52

25-04-2019 дата публикации

Tissue Use for Repair of Injury

Номер: US20190117373A1

Автор: Anz Adam, Jordan Steve, Schmeiding Reinhold, Shepard David, Tokish John

Принадлежит:

The present disclosure describes methods of treating an injury in a subject using placental tissue streamers, engineered tissue placental tissue hybrids, suture placental tissue hybrids, placental tissue patch hybrids, and tissue hybrids, and the use of these compositions to repair, treat, or support an injury or degenerative process in a subject. 1. A method of anterior cruciate ligament repair comprising:a) wrapping amnion tissue around a tissue graft to form a wrapped graft;b) placing at least one cerclage stitch at either end of the amnion tissue and one running stitch at the end of the wrapped graft to form a water-tight compartment;c) inserting the wrapped graft into a knee joint; andd) adding platelet rich plasma or bone marrow concentrate to the water-tight compartment between the amnion tissue and the tissue graft.2. The method of claim 1 , wherein the amnion is wrapped more than once around the tissue graft.3. A method of ligament repair comprising:a) wrapping placental tissue around a tissue graft to form a wrapped graft;b) placing at least one stitch at either end of the placental tissue and one stitch at the end of the wrapped graft to form at least one water-tight compartment; andc) adding a biological agent to the at least one water-tight compartment.4. The method of claim 3 , wherein the at least one water-tight compartment is between the placental tissue and the tissue graft.5. The method of claim 3 , wherein the biological agent is platelet rich plasma claim 3 , bone marrow concentrate claim 3 , viscous amnion claim 3 , a growth factor claim 3 , or stem cells.6. The method of claim 3 , wherein the placental tissue is wrapped around the tissue graft more than once.7. The method of claim 6 , wherein the biological agent is added to a compartment between different layers of the placental tissue.8. The method of claim 3 , wherein the placental tissue is amnion claim 3 , chorion claim 3 , or umbilical cord.9. The method of claim 3 , wherein the ...

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Номер записи: 53

25-04-2019 дата публикации

Bioengineered vocal fold mucosa for functional voice restoration

Номер: US20190117384A1

Автор: Changying Ling, Nathan Welham

Принадлежит: WISCONSIN ALUMNI RESEARCH FOUNDATION

An engineered vocal fold mucosa, including an engineered lamina propria layer and an engineered squamous epithelium layer, is disclosed. The engineered lamina propria is made by seeding and culturing human vocal fold fibroblasts within a polymerized collagen scaffold, and the engineered squamous epithelium is made by culturing human vocal fold epithelial cells on the scaffold surface. The resulting engineered vocal fold mucosa is not immunogenic, and is capable of exhibiting the vibratory function and acoustic output of a native vocal fold mucosa. Accordingly, the engineered vocal fold mucosa may be implanted into the larynx to treat voice impairment.

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Номер записи: 54

27-05-2021 дата публикации

BIOCOMPATIBLE TEXTILE MESH AND TISSUE CONSTRUCTS FROM MANICARIA SACCIFERA, METHODS OF GROWING CELLS AND TISSUES, AND METHODS OF TREATING SUBJECTS WITH THE BIOCOMPATIBLE TEXTILE MESH AND TISSUE CONSTRUCTS

Номер: US20210154371A1

Автор: ALLEN Josephine, NINO Juan Claudio

Принадлежит:

Various embodiments of biocompatible textile mesh and tissue constructs from , methods of growing cells and tissues using the -based textile mesh/tissue scaffolds, and methods of treating subjects with the biocompatible textile mesh and tissue constructs are described. The mesh, constructs and methods can include a biocompatible textile mesh made from a naturally woven fiber mat from a palm bract that has been treated to remove oils and lignin from the surface of palm fibers in the mat and seeded with a population of cells. An engineered, biocompatible tissue construct, a method of growing mammalian tissue in vivo, and a method of treating a subject are also described. 1. A method of growing mammalian tissue comprising:{'i': 'Manicaria saccifera', 'providing a biocompatible textile mesh made from a naturally woven fiber mat from a palm bract, wherein the fiber mat has been treated to remove oils and lignin from the surface of palm fibers in the mat; and'}seeding the biocompatible textile mesh with a population of mammalian cells, andgrowing the cells on the mesh to form a tissue.2. The method of claim 1 , further comprising autoclaving the treated fiber mat to sterilize the mat prior to seeding with the population of cells.3. The method of claim 2 , wherein autoclaving is at a temperature of about 105 to about 134 for a time of about 15 min or more.4. The method of claim 1 , wherein treatment to remove oils and lignin comprises washing with water and an alkali solution to reduce hydrophobicity of the fibers.5Manicaria saccifera. The method of claim 1 , wherein the biocompatible textile mesh consists essentially of a portion of a naturally woven fiber mat cut from a bract of that has been treated with water and alkali.6. The method of claim 1 , wherein the treated fiber mat of the biocompatible textile mesh has not been functionalized with additional proteins.7. The method of claim 1 , wherein growing the cells comprises culturing the seeded mesh in a compatible ...

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Номер записи: 55

12-05-2016 дата публикации

MATRIX AND IMPLANT FOR TISSUE ENGINEERING

Номер: US20160130558A1

Автор: BAER Hans U.

Принадлежит:

A porous matrix for tissue engineering has a first biodegradable and biocompatible polymer component forming a three-dimensional primary structure with primary pores, and further includes a second biodegradable and biocompatible polymer component other than the first polymer component selected from the group of collagens, laminin, fibronectin and mixtures thereof, wherein the second polymer component forms a three-dimensional secondary structure with secondary pores, the secondary structure being contained within the interior space of at least a part of the primary pores. 1. A porous matrix for tissue engineering comprising a first biodegradable and biocompatible polymer component forming a three-dimensional primary structure with primary pores , and further comprising a second biodegradable and biocompatible polymer component other than the first polymer component selected from the group consisting of collagens , laminin , fibronectin and mixtures thereof , wherein the second polymer component forms a three-dimensional secondary structure with secondary pores , the secondary structure being contained within the interior space of at least a part of the primary pores.2. Matrix according to claim 1 , wherein the first polymer component is selected from the group consisting of poly(glycolic acid) claim 1 , poly(lactic acid) claim 1 , poly(glycolic acid-lactic acid) and mixtures thereof.3. Matrix according to claim 1 , wherein the second polymer component is collagen.4. Matrix according to claim 1 , wherein the primary pores have an average pore size diameter of 150 μm to 300 μm.5. Matrix according to claim 4 , wherein the secondary pores have an average pore size diameter smaller than the average pore size diameter of the primary pores and being in the range from 50 μm to 290 μm.6. Matrix according to claim 1 , comprising a porous base layer and a porous cell-embedding layer claim 1 , the average pore size of the pores in the base layer being smaller than the one of ...

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Номер записи: 56

01-09-2022 дата публикации

NANO SCALE DECORATION OF SCAFFOLD-FREE MICROTISSUE USING FUNCTIONALISED GOLD NANOSTRUCTURES

Номер: US20220273845A1

Автор: Migrino Raymond, Navaei Ali, Nikkhah Mehdi

Принадлежит:

A method for regeneration or repair of an infarcted myocardium including an infarcted region in an animal comprising injecting into the animal a composition including one or more gold nanostructures is disclosed. 1. A method for regeneration or repair of an infarcted myocardium including an infarcted region in an animal comprising injecting into the animal a composition comprising:one or more gold nanostructures linked to one or more cell adhesion peptides;a plurality of cardiac myocytes or cardiac myoblasts, wherein the cardiac myocytes or cardiac myoblasts are conjugated to the one or more gold nanostructures, wherein the plurality of cardiac myocytes or cardiac myoblasts are arranged in a cluster; anda plurality of fibroblasts, wherein the fibroblasts are arranged in at least one layer of fibroblasts that substantially surrounds the cluster of gold-nanostructure-conjugated cardiac myocytes or gold-nanostructure-conjugated cardiac myoblasts, wherein optionally, the gold nanostructures are further linked to one or more anti-inflammatory peptides, one or more antiapoptotic peptides, one or more antinecrotic peptides, one or more antioxidant particles, one or more liposomes, one or more nanoliposomes, one or more microRNAs, or one or more siRNAs.2. The method of claim 1 , wherein the composition is delivered via catheter to the infarcted region.3. The method of claim 1 , wherein the composition is injected within the infarcted region.4. The method of claim 1 , wherein the one or more gold nanostructures are additionally linked to one or more anti-inflammatory peptides.5. The method of claim 1 , wherein the one or more gold nanostructures are wires claim 1 , rods or plates.6. The method of claim 1 , wherein the cardiac myocytes are human-induced pluripotent-stem-cell-derived cardiac myocytes.7. The method of claim 6 , wherein the one or more gold nanostructures are additionally linked to one or more vasculogenic peptides.8. The method of claim 7 , wherein the one or ...

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Номер записи: 57

19-05-2016 дата публикации

3D TISSUE-ENGINEERED BONE MARROW FOR PERSONALIZED THERAPY AND DRUG DEVELOPMENT

Номер: US20160136327A1

Автор: Azab Abdel Kareem, de la Puente Pilar

Принадлежит:

A tissue-engineered bone marrow for personalized therapy of a patient is described. The tissue-engineered bone marrow includes an autologous fibrin scaffold and a plurality of patient-derived cells isolated from the patient's bone marrow. The autologous fibrin scaffold is made using fibrinogen isolated from the patient's bone marrow. The plurality of patient-derived cells may include cells associated with a hematological or metastatic malignancy, bone marrow stromal cells, and endothelial cells. The patient-derived cells are cultured on the autologous fibrin scaffold to create the tissue-engineered bone marrow. The tissue-engineered bone marrow may be used for personalized drug screening. 1. A tissue-engineered bone marrow for personalized therapy of a patient comprising:an autologous fibrin scaffold comprising fibrinogen isolated from the patient's bone marrow; anda plurality of patient-derived cells isolated from the patient's bone marrow, the patient-derived cells selected from the group consisting of cells associated with a hematological or metastatic malignancy, bone marrow stromal cells, endothelial cells, and combinations thereof,wherein the patient-derived cells are cultured on the autologous fibrin scaffold.2. The tissue-engineered bone marrow of claim 1 , wherein the autologous fibrin scaffold further comprises an antifibrinolytic agent.3. The tissue-engineered bone marrow of claim 1 , wherein the autologous fibrin scaffold further comprises a patient-derived culture compound extracted from the patient's bone marrow claim 1 , the patient-derived culture compound selected from the group consisting of: fibronectin claim 1 , at least one growth factor claim 1 , platelets claim 1 , at least one cytokine claim 1 , at least one enzyme claim 1 , and combinations thereof.4. The tissue-engineered bone marrow of claim 1 , further comprising a drug.5. The tissue-engineered bone marrow of claim 4 , wherein the autologous fibrin scaffold further comprises a gradient of ...

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Номер записи: 58

03-06-2021 дата публикации

Cell-Containing Hydrogel Body and Method for Producing Same

Номер: US20210163918A1

Автор: FUKUDA Junji, Kageyama Tatsuto

Принадлежит:

Provided are a cell-containing hydrogel body and a method of producing the same, which enable simple and effective control of the size of a boundary surface for an interaction between cells. The method of producing a cell-containing hydrogel body includes: forming, under a gas phase, a first hydrogel droplet on a surface of a substrate, the first hydrogel droplet containing first cells being dispersed therein and a first hydrogel polymer; forming, under a gas phase, a second hydrogel droplet on the surface, the second hydrogel droplet containing second cells being dispersed therein and a second hydrogel polymer, the second hydrogel droplet being combined with the first hydrogel droplet; and forming, under a gas phase, a cell-containing hydrogel body on the surface by gelling a hydrogel droplet-combined body including a first droplet portion derived from the first hydrogel droplet and a second droplet portion derived from the second hydrogel droplet. 1. A method of producing a cell-containing hydrogel body , comprising:forming, under a gas phase, a first hydrogel droplet on a surface of a substrate, the first hydrogel droplet containing first cells being dispersed therein and a first hydrogel polymer;forming, under a gas phase, a second hydrogel droplet on the surface, the second hydrogel droplet containing second cells being dispersed therein and a second hydrogel polymer, the second hydrogel droplet being combined with the first hydrogel droplet; andforming, under a gas phase, a cell-containing hydrogel body on the surface by gelling a hydrogel droplet-combined body including a first droplet portion derived from the first hydrogel droplet and a second droplet portion derived from the second hydrogel droplet.2. The method of producing a cell-containing hydrogel body according to claim 1 , further comprising culturing the first cells and the second cells in the cell-containing hydrogel body.3. The method of producing a cell-containing hydrogel body according to claim ...

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Номер записи: 59

18-05-2017 дата публикации

Methods of using regenerative cells in the treatment of renal diseases and disorders

Номер: US20170136066A1

Автор: Eric Daniels, John K. Fraser, Marc H. Hedrick

Принадлежит: Cytori Therapeutics Inc

Cells present in processed lipoaspirate tissue are used to treat patients, including patients with renal conditions, diseases or disorders. Methods of treating patients include processing adipose tissue to deliver a concentrated amount of stem cells obtained from the adipose tissue to a patient. The methods may be practiced in a closed system so that the stem cells are not exposed to an external environment prior to being administered to a patient. Accordingly, in a preferred method, cells present in processed lipoaspirate are placed directly into a recipient along with such additives necessary to promote, engender or support a therapeutic renal benefit.

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Номер записи: 60

18-05-2017 дата публикации

AUTO-GRAFTING

Номер: US20170136148A1

Автор: Berriman Sandra, Tumey David

Принадлежит:

An apparatus and method for the production of substitute skin that advantageously reduces the amount of donor dermal cells needed from non-wound areas of a patient having a wound to be auto-grafted is reduced by using all of the harvested skin cells. A 3D printer is used to construct a wound graft product from the harvested skin cells without wasting any of the harvested skin cells. In a case of an irregularly shaped wound, wastage of harvested skin associated with trimming is avoided. 148-. (canceled)49. An auto-grafting method for treating a wound of a patient , comprising:harvesting a quantity of skin cells from a patient;auto-grafting onto the wound of the patient the quantity of harvested skin cells, with the quantity of autografted harvested skin cells being substantially equal to the quantity of harvested skin cells.50. The auto-grafting method of claim 49 , wherein the auto-grafting step comprises auto-grafting a three-dimensional irregularly-shaped skin graft product.51. The auto-grafting method of claim 49 , further comprising constructing claim 49 , via operation of a three-dimensional printer claim 49 , a skin graft product comprising the quantity of harvested skin cells.5221. The method of claim claim 49 , further comprising printing insulin into the skin graft product being constructed.5321. The method of claim claim 49 , further comprising printing or spraying amniotic membrane into the skin graft product being constructed. The invention relates to the medical arts, more particularly, to tissue engineering especially tissue engineering in which three-dimensional printing technology is used.Healing wounds is a complex process of tissue repair and regeneration in response to injury. The healing response in skin wounds attempts to reconstitute a tissue similar to the original damaged one and this is accomplished via the concerted action of numerous skin cell types, collagens, cytokines, growth factors (GFs), chemokines, cell surface and adhesion ...

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Номер записи: 61

09-05-2019 дата публикации

ENGINEERING MULTILEVEL CELL SHEET-DERIVED BLOOD VESSELS

Номер: US20190134274A1

Автор: von Bornstaedt Daniel, Wang Hanjay, Woo Y. Joseph

Принадлежит:

Engineered multilevel cell sheet-derived blood vessels and methods of preparing and using them are disclosed. Blood vessels are generated by wrapping cell sheets around a rod-like device, such as an angiocath needle, to form a tube, which is stabilized with a cyanoacrylate membrane or fibrin glue followed by endothelialization. Such engineered blood vessels can be implanted in tissue and used in vascular surgery as vascular bypass or interposition grafts as well as for vascularization and perfusion of tissue or organs prior to transplant. 1. A method of making a tissue-engineered blood vessel comprising:a) culturing fibroblasts and smooth muscle cells to form one or more confluent cell sheets;b) wrapping said one or more cell sheets around a rod-like device to form a tube;c) stabilizing the tube formed from the cell sheets with a cyanoacrylate membrane or fibrin glue;d) endothelialization of the tube formed from the cell sheets by culturing with endothelial cells; ande) removing the rod-like device to form the tissue-engineered blood vessel.2. The method of claim 1 , wherein the fibroblasts and smooth muscle cells are from a human subject.3. The method of claim 1 , wherein the endothelial cells are human umbilical vein endothelial cells.4. The method of claim 1 , wherein the diameter of the rod-like device is less than or equal to 1 mm.5. The method of claim 1 , wherein the rod-like device is a mandrel or needle.6. The method of claim 5 , wherein the needle is an angiocath needle.7. The method of claim 5 , wherein the needle has a gauge of at least 11 claim 5 , at least 16 claim 5 , at least 18 claim 5 , at least 20 claim 5 , at least 22 claim 5 , or at least 22.5.8. The method of claim 7 , wherein the needle has a gauge ranging from 11 to 24.9. The method of claim 8 , wherein the needle has a gauge of 22.5.10. The method of claim 1 , wherein at least 4 claim 1 , 5 claim 1 , 6 claim 1 , 7 claim 1 , 8 claim 1 , 9 claim 1 , 10 claim 1 , 11 claim 1 , or 12 cell sheets ...

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Номер записи: 62

09-05-2019 дата публикации

Folding Biological Tissue Via Programmed Cellular Contractility

Номер: US20190136178A1

Автор: Gartner Zev Jordan, Hughes Alex James

Принадлежит:

The present disclosure provides methods and systems for generating biological tissues that are configured for folding into a pre-determined three-dimensional form. The present disclosure utilizes contractile cells for folding a biological tissue into a three-dimensional shape. The methods include disposing a pattern of contractile cells on a surface that includes fibers actuated by the contractile cells and folding of the surface by the action of the contractile cells on the fibers. Tissues generated using the methods and systems of the present disclosure are also provided. 1. A method of making a planar biological tissue configured for folding into a three-dimensional shape , the method comprising: disposing a pattern of nucleic acids on a surface of a substrate; and', 'contacting the patterned nucleic acids under hybridization conditions with a suspension of the contractile cells, wherein the contractile cells comprise cell surface-attached nucleic acids complementary to the patterned nucleic acids, and wherein the cell surface-attached nucleic acids hybridize to the patterned nucleic acids to generate patterned contractile cells on the surface of the substrate;, 'patterning contractile cells on a surface of a substrate, comprisingcontacting the patterned contractile cells on the surface of the substrate with a polymer matrix comprising fibers thereby embedding the patterned contractile cells into the polymer matrix;removing the polymer matrix from the surface of the substrate, wherein the patterned contractile cells are retained in the polymer matrix upon removal thereby generating a planar biological tissue configured for folding into a three-dimensional shape;contacting the planar biological tissue with a culture medium; andincubating the planar biological tissue in suspension in the culture medium for a period of time sufficient for action of the contractile cells on the fibers for folding the tissue into a three-dimensional shape.2. The method of claim 1 , ...

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Номер записи: 63

24-05-2018 дата публикации

CELL STRUCTURE AND METHOD FOR PRODUCING CELL STRUCTURE

Номер: US20180140745A1

Автор: Nakamura Kentaro

Принадлежит: FUJIFILM Corporation

An object of the present invention is to provide a cell structure which can be produced within a short period of time and has a predetermined or larger size, and a method for producing the above-described cell structure. According to the present invention, there is provided a cell structure including: a biocompatible macromolecular block; and two or more kinds of cells, in which a plurality of the biocompatible macromolecular blocks are arranged in gaps between a plurality of the cells, and in which the two or more kinds of cells contain at least one kind of first cell selected from the group consisting of vascular endothelial cells, cardiac muscle cells, pancreatic islet cells, liver cells, epithelial cells, endothelial cells, nerve cells, embryonic stem cells, induced pluripotent stem cells, corneal epithelial cells, and retinal pigment epithelial cells, and at least one kind of second cell selected from the group consisting of mesenchymal cells, stromal cells, fibroblasts, smooth muscle cells, myoblasts, mesenchymal stem cells, adipose-derived stem cells, and umbilical cord-derived stem cells. 2. The method for producing a cell structure according to claim 1 ,wherein a ratio of the number of cells of the first cell to the second cell is 9:1 to 1:99.3. The method for producing a cell structure according to claim 1 ,wherein a size of the biocompatible macromolecular block is 10 μm to 300 μm.4. The method for producing a cell structure according to claim 1 ,wherein a thickness or a diameter of the cell structure is 400 μm to 3 cm.5. The method for producing a cell structure according to claim 1 ,{'sup': 3', '3, 'wherein a tap density of the biocompatible macromolecular block is 10 mg/cmto 500 mg/cm.'}6. The method for producing a cell structure according to claim 1 ,wherein a biocompatible macromolecule is cross-linked in the biocompatible macromolecular block.7. The method for producing a cell structure according to claim 6 ,wherein the cross-linking degree of the ...

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Номер записи: 64

02-06-2016 дата публикации

Methods for Development and Use of Minimally Polarized Function Cell Micro-Aggregate Units in Tissue Applications Using LGR4, LGR5 and LGR6 Expressing Epithelial Stem Cells

Номер: US20160151540A1

Автор: Denver M. Lough

Принадлежит: Individual

Provided herein are constructs of micro-aggregate multicellular, minimally polarized grafts containing Leucine-rich repeat-containing G-protein coupled Receptor (LGR) expressing cells for wound therapy applications, tissue engineering, cell therapy applications, regenerative medicine applications, medical/therapeutic applications, tissue healing applications, immune therapy applications, and tissue transplant therapy applications which preferably are associated with a delivery vector/substrate/support/scaffold for direct application.

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Номер записи: 65

02-06-2016 дата публикации

METHODS AND DEVICES FOR CELLULAR TRANSPLANTATION

Номер: US20160151541A1

Автор: Hasilo Craig, Haworth Daniel Nicholas, Leushner Justin, Shohet Simon, Siroen Delfina Maria Mazzuca, Toleikis Philip Michael

Принадлежит:

Devices and methods for transplanting cells in a host body are described. The cell comprises a porous scaffold that allows ingrowth of vascular and connective tissues, a plug or plug system configured for placement within the porous scaffold, and a seal configured to enclose a proximal opening in the porous scaffold. The device may further comprise a cell delivery device for delivering cells into the porous scaffold. The method of cell transplantation comprises a two step process. The device is incubated in the host body to form a vascularized collagen matrix around a plug positioned within the porous scaffold. The plug is then retracted from the porous scaffold, and cells are delivered into the vascularized space created within the porous scaffold. 185-. (canceled)86. A device for implanting cells in a host body , comprising:a porous scaffold comprising a polypropylene mesh forming the walls of at least one chamber, wherein the chamber comprises an opening at either or both of a proximal end and a distal end of the chamber, wherein the proximal end and the distal end are separated by a lumen that is bounded by the walls, and wherein the porous scaffold has pores sized to facilitate growth of vascular and connective tissues around and through the walls of the at least one chamber;at least one removable, non-porous two-plug system configured to be positioned within the lumen of the at least one chamber, wherein the two-plug system comprises an outer plug configured to be positioned within the lumen of the at least one chamber and an inner plug configured to be positioned within the outer plug, and wherein the two-plug system extends along the lumen of the chamber;at least one seal configured to enclose either or both the proximal end and the distal end of the chamber; andcells within the chamber, wherein the cells comprise differentiated stem cells or encapsulated cells.87. The device of claim 86 , wherein the cells are encapsulated in alginate claim 86 , a ...

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Номер записи: 66

07-05-2020 дата публикации

SELF-ASSEMBLING MULTICELLULAR BODIES AND METHODS OF PRODUCING A THREE-DIMENSIONAL BIOLOGICAL STRUCTURE USING THE SAME

Номер: US20200140809A1

Автор: FORGACS Gabor, MARGA Francoise Suzanne, NOROTTE Cyrille

Принадлежит:

Structures and methods for tissue engineering include a multicellular body including a plurality of living cells. A plurality of multicellular bodies can be arranged in a pattern and allowed to fuse to form an engineered tissue. The arrangement can include filler bodies including a biocompatible material that resists migration and ingrowth of cells from the multicellular bodies and that is resistant to adherence of cells to it. Three-dimensional constructs can be assembled by printing or otherwise stacking the multicellular bodies and filler bodies such that there is direct contact between adjoining multicellular bodies, suitably along a contact area that has a substantial length. The direct contact between the multicellular bodies promotes efficient and reliable fusion. The increased contact area between adjoining multicellular bodies also promotes efficient and reliable fusion. Methods of producing multicellular bodies having characteristics that facilitate assembly of the three-dimensional constructs are also provided. 1174.-. (canceled)175. A method of producing a multicellular body comprising a plurality of living cells , the method comprising:shaping a cell paste comprising a plurality of living cells in a device that holds the cell paste in a three-dimensional shape; andincubating the shaped cell paste in a controlled environment while it is held in said three-dimensional shape to produce a cohesive body that is capable of supporting itself on a flat surface.176. The method of claim 175 , further comprising producing the cell paste by mixing a plurality of living cells with a tissue culture medium.177. The method of claim 176 , wherein the producing comprises compacting the living cells.178. The method of claim 177 , wherein the compacting comprises centrifuging a cell suspension comprising the plurality of living cells.179. The method of claim 175 , wherein the shaping comprises retaining the cell paste in a first shaping device to allow the cells to ...

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Номер записи: 67

01-06-2017 дата публикации

SELF-ASSEMBLING MULTICELLULAR BODIES AND METHODS OF PRODUCING A THREE-DIMENSIONAL BIOLOGICAL STRUCTURE USING THE SAME

Номер: US20170152474A1

Автор: FORGACS Gabor, MARGA Francoise Suzanne, NOROTTE Cyrille

Принадлежит:

Structures and methods for tissue engineering include a multicellular body including a plurality of living cells. A plurality of multicellular bodies can be arranged in a pattern and allowed to fuse to form an engineered tissue. The arrangement can include filler bodies including a biocompatible material that resists migration and ingrowth of cells from the multicellular bodies and that is resistant to adherence of cells to it. Three-dimensional constructs can be assembled by printing or otherwise stacking the multicellular bodies and filler bodies such that there is direct contact between adjoining multicellular bodies, suitably along a contact area that has a substantial length. The direct contact between the multicellular bodies promotes efficient and reliable fusion. The increased contact area between adjoining multicellular bodies also promotes efficient and reliable fusion. Methods of producing multicellular bodies having characteristics that facilitate assembly of the three-dimensional constructs are also provided. 1174-. (canceled)175. A method of producing a multicellular body comprising a plurality of living cells , the method comprising:shaping a cell paste comprising a plurality of living cells in a device that holds the cell paste in a three-dimensional shape; andincubating the shaped cell paste in a controlled environment while it is held in said three-dimensional shape to produce a cohesive body that is capable of supporting itself on a flat surface.176. The method of claim 175 , further comprising producing the cell paste by mixing a plurality of living cells with a tissue culture medium.177. The method of claim 176 , wherein the producing comprises compacting the living cells.178. The method of claim 177 , wherein the compacting comprises centrifuging a cell suspension comprising the plurality of living cells.179. The method of claim 175 , wherein the shaping comprises retaining the cell paste in a first shaping device to allow the cells to ...

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Номер записи: 68

07-06-2018 дата публикации

Compositions and methods for urinary bladder regeneration

Номер: US20180154045A1

Автор: Arun Sharma, Derek Matoka, Earl Cheng, Natalie Fuller, Partha Hota

Принадлежит: Northwestern University

The present invention provides compositions and methods for the regeneration of tissue. In particular, the present invention provides mesenchymal stem cells (MSCs) and endothelial progenitor cells (EPCs) for bladder regeneration.

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Номер записи: 69

08-06-2017 дата публикации

TISSUE TRANSPLANT COMPOSITIONS AND METHODS FOR USE

Номер: US20170157291A1

Автор: Crawford Keith D., Garvey John M., Layton Pamela

Принадлежит:

Provided are transplants and methods for augmenting formation and restoration of organ and tissue, for example, bone formation, by administering autologous or allogeneic human embryonic-like adult stem cells (ELA cells). Also provided is a method for augmenting formation of tissues and organs by administering a transplant having ELA stem cells or combination of ELA stem cells. 1. A transplant composition comprising: a T-cell- or NK-cell-suppressive amount of a non-expanded population of human early lineage adult (ELA) stem cells , an immune cell population comprising plasmacytoid dendritic cells , and a cryopreservative , wherein the human ELA stem cells express at least one of Oct4 , Nanog and Sox2 , and do not detectably express CD13 , CD45 , CD90 or CD34 , and wherein the transplant composition is without detectable erythrocyte cells.2. The transplant composition of claim 1 , wherein the transplant is an allograft.3. The transplant composition of claim 2 , wherein the allograft is not MHC matched to the human transplant recipient.4. The transplant composition of claim 1 , wherein the transplant includes at least one component selected from the group consisting of plasma claim 1 , cell culture medium claim 1 , an antibacterial agent claim 1 , a growth factor claim 1 , a vitamin claim 1 , and a hormone.5. The transplant composition of claim 1 , further comprising a carrier having a matrix claim 1 , wherein the matrix conforms substantially to its insertion site and provides a structurally stable claim 1 , three dimensional surface that retains the transplant and supports ingrowth of ELA stem cells into the matrix at the insertion site.6. The transplant composition of claim 1 , wherein the transplant promotes the formation of a tissue selected from the group consisting of: connective tissue; bone; and dermal tissue.7. The transplant composition of claim 1 , wherein the human ELA stem cell numbers in the transplant comprise about 5000 to about 5×10human ELA stem ...

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Номер записи: 70

14-05-2020 дата публикации

BIOENGINEERED ALLOGENEIC BLOOD VESSEL

Номер: US20200147272A1

Автор: Olausson Michael, Sumitran-Holgersson Suchitra

Принадлежит: VeriGraft AB

The present invention relates to methods for recellurization of blood vessels. This method is particularly useful for producing an allogeneic vein, wherein a donor vein is decellularized and then recellularized using whole blood or bone marrow stem cells. The allogeneic veins produced by the methods disclosed herein are particularly advantageous for implantation or transplantation into patients with vascular diseases. 131.-. (canceled)32. A method of decellularizing a blood vessel comprising treating the blood vessel to be decellularized with a first solution comprising Triton X 100 , followed by treating the blood vessel to be decellularized with a second solution comprising tri-n-butyl phosphate.33. The method of claim 32 , wherein one or more of the solutions further comprises a DNase.34. The method of claim 33 , wherein the DNase is DNase I.35. The method of claim 32 , wherein the treatment is performed at least twice with a washing step in between treatment with each solution.36. The method of claim 35 , wherein the washing is performed with PBS.37. The method of claim 32 , wherein the blood vessel is a vein or an artery.38. The method of claim 32 , wherein the first solution comprises 1% Triton X 100 and the second solution comprises 1% tri-n-butyl phosphate.39. The method of claim 32 , wherein claim 32 , following the treatment claim 32 , the decellularized blood vessel is free of cell nuclei and HLA class I and II antigens.40. A decellularized blood vessel produced by the method of . This application is a continuation of U.S. application Ser. No. 15/169,868, filed on Jun. 1, 2016, which is a continuation of U.S. application Ser. No. 14/723,727, filed May 28, 2015 (now U.S. Pat. No. 9,433,706), which is a continuation of U.S. application Ser. No. 14/364,756, filed Jun. 12, 2014 (now U.S. Pat. No. 9,090,879), which is a national stage application, filed under 35 U.S.C. § 371, of International Application No. PCT/IB2013/000873, filed Mar. 1, 2013, which claims ...

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Номер записи: 71

24-06-2021 дата публикации

METHODS FOR TISSUE DECELLULARIZATION

Номер: US20210187164A1

Автор: Bonfanti Paola, Gjinovci Asllan

Принадлежит: UCL BUSINESS LTD

The present invention provides A method of producing a decellularised extracellular matrix (ECM) scaffold of at least a portion of a lobular organ with no common artery, the method comprising: a) closing afferent blood vessels to substantially seal a target lobular organ or portion thereof with no common and/or major artery within a non-human donor or a dead/brain dead human donor; b) optionally: (i) cleaning coagulum and/or blood from at least a portion of the closed afferent blood vessels; and/or (ii) perfusing the organ or portion thereof to confirm closure of the afferent blood vessels; c) removing the sealed organ or portion thereof from the donor; and d) perfusing the sealed organ or portion thereof with detergent and enzymatic solutions to obtain the decellularised ECM scaffold. Methods for producing an artificial organ, and artificial organs produced by the methods are also provided. 1. A method of producing a decellularised extracellular matrix (ECM) scaffold of at least a portion of a lobular organ with no common artery , the method comprising:a) closing afferent blood vessels to substantially seal a target lobular organ, or a portion thereof, with no common and/or major artery within a non-human donor or a dead/brain dead human donor;b) optionally: (i) cleaning coagulum and/or blood from at least a portion of the closed afferent blood vessels; and/or (ii) perfusing the target lobular organ or the portion thereof to confirm closure of the afferent blood vessels to form a sealed organ;c) removing the sealed organ or a portion thereof from the non-human donor or a dead/brain dead human donor; andd) perfusing the sealed organ or the portion thereof with a detergent and enzymatic solutions to obtain the decellularised ECM scaffold.2. The method according to claim 1 , wherein the detergent is sodium deoxycholate (SDC) claim 1 , sodium dodecyl sulphate (SDS) claim 1 , Triton X-100 claim 1 , or a combination thereof.3. The method according to claim 1 , wherein ...

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Номер записи: 72

01-07-2021 дата публикации

METHOD FOR PRODUCING REGENERATED HAIR FOLLICLE PRIMORDIUM

Номер: US20210196861A1

Автор: MORI Yutaka, TOYOSHIMA Koh-ei, Tsuji Takashi

Принадлежит:

The present invention provides a method for producing regenerated hair follicle primordium that allows production of regenerated hair follicle primordium more easily and in larger amounts compared to conventional production methods. 1. A method for producing regenerated hair follicle primordium , characterized in that it comprises a step of obtaining regenerated hair follicle primordium by culturing a first population of cells comprising epithelial cells and a second population of cells comprising mesenchymal cells while allowing them to be in contact ,whereinat least either one of said first population of cells and said second population of cells has formed cell aggregates before said contact, anda culture support is not used when contacting the other population of cells with said cell aggregate.2. The production method according to claim 1 , further comprising prior to said contact a step of forming a first cell aggregate of said epithelial cells aggregated claim 1 , as said first population of cells.3. The production method according to claim 2 , wherein the step of forming said first cell aggregate comprises obtaining a spheroid of epithelial cells.4. The production method according to claim 1 , further comprising prior to said contact a step of forming a second cell aggregate of said mesenchymal cells aggregated claim 1 , as said second population of cells.5. The production method according to claim 4 , wherein the step of forming said second cell aggregate comprises obtaining a spheroid of mesenchymal cells.6. The production method according to claim 2 , wherein at least one of the step of forming said first cell aggregate and the step of forming said second cell aggregate comprises aggregating said epithelial cells or said mesenchymal cells in a recess configured so that said epithelial cells or said mesenchymal cells are accumulated at the bottom.7. The production method according to claim 6 , wherein said recess has a V-shaped or a U-shaped bottom.8. The ...

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Номер записи: 73

22-06-2017 дата публикации

ENGINEERED CARDIAC DERIVED COMPOSITIONS AND METHODS OF USE

Номер: US20170173215A1

Автор: Blazeski Adriana, Tung Leslie

Принадлежит:

The present invention establishes a new standard for investigative studies of patient-specific, genetic cardiac diseases at a functional, tissue level by creating a novel platform for the study of cardiac related diseases, including cardiac conduction dysfunction, arrhythmias and depressed contractility for example. Provided herein are novel compositions of human engineered heart slices (EHS) formed from thin slices of decellularized cardiac tissue. Also included are compositions comprising a hybrid of decellularized tissue and organotypic organ slice technology. Intact mammalian hearts are precision cut to obtain thin slices in a range of thicknesses, decellularized, and seeded with various mammalian cells which can be from a variety of sources. Methods of investigation of many diseases and methods of use of these compositions for screening compounds for therapeutic purposes are also provided. 1. A composition comprising a 3D biocompatible decellularized mammalian cardiac tissue slice matrix having an upper and a lower surface , the matrix being capable of sustaining cellular growth.2. The composition of claim 1 , wherein the composition further comprises a plurality of mammalian cells selected from the group consisting of smooth muscle myocytes claim 1 , striated muscle myocytes claim 1 , cardiac myocytes claim 1 , fibroblasts claim 1 , neurons claim 1 , vascular endothelial cells claim 1 , cardiac progenitor cells and stem cells on at least one surface of the matrix.3. The composition of claim 2 , wherein the cardiac slice matrix can be derived from one or more different regions of the heart.4. The composition of claim 3 , wherein the heart regions are selected from the group consisting of the atria claim 3 , ventricles claim 3 , septum claim 3 , epicardium claim 3 , midmyocardium claim 3 , and endocardium.5. The composition of claim 2 , wherein the cardiac slice matrix can be derived from one or more tissues of differing ages.6. The composition of claim 2 , ...

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Номер записи: 74

30-06-2016 дата публикации

SKIN SUBSTITUTES AND METHODS FOR HAIR FOLLICLE NEOGENESIS

Номер: US20160184481A1

Автор: Darling Thomas N., LI Shaowei, Thangapazham Rajesh

Принадлежит: The Henry M. Jackson Foundation for the Advancement of Military Medicine, Inc.

This invention provides compositions in the form of skin substitutes comprising epithelial cells and mesenchymal cells, wherein the mesenchymal cells are not isolated from the occipital or nape region of the scalp, as well as methods for using the same. 1113-. (canceled)114. A skin substitute comprising epithelial cells and mesenchymal cells , wherein the mesenchymal cells area. neural crest-derived mesenchymal cells orb. scalp- or face-derived mesenchymal cells, wherein the mesenchymal cells are not derived from an occipital or nape region of the scalp.115. The skin substitute of claim 114 , wherein the epithelial cells are keratinocytes.116. The skin substitute of claim 114 , wherein the mesenchymal cells are hair follicle dermal cells.117. The skin substitute of claim 116 , wherein the hair follicle dermal cells are dermal papilla cells or dermal sheath cells.118. The skin substitute of claim 116 , wherein the hair follicle dermal cells are derived from scalp or face.119. The skin substitute of claim 118 , wherein the hair follicle dermal cells are derived from a frontal claim 118 , temporal claim 118 , mid scalp claim 118 , top of head claim 118 , vertex claim 118 , or parietal region of the scalp.120. The skin substitute of claim 114 , wherein the epithelial cells are from a first or second passage.121. The skin substitute of claim 114 , wherein the mesenchymal cells are from a first claim 114 , second claim 114 , third claim 114 , or fourth passage.122. The skin substitute of claim 120 , wherein the epithelial cells are passaged in keratinocyte-conditioned medium.122. The skin substitute of claim 121 , wherein the mesenchymal cells are passaged in keratinocyte-conditioned medium.123. The skin substitute of claim 114 , wherein the epithelial cells and the mesenchymal cells are human.124. The skin substitute of claim 114 , further comprising collagen.125. A method for inducing hair follicle growth or hair follicle neogenesis claim 114 , comprising delivering to ...

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Номер записи: 75

04-06-2020 дата публикации

COMPOSITIONS AND METHODS FOR IMPROVING CARDIAC FUNCTION

Номер: US20200171206A1

Автор: Chinyere Ikeotunye R., Goldman Steven, Koevary Jennifer W., Lancaster Jordan J.

Принадлежит:

The present invention provides compositions and methods for improving cardiac function. Specifically, the present invention provides compositions and methods for treating a subject having a disorder or condition associated with aberrant cardiac tissue function, comprising contacting a patient having a disorder or condition associated with aberrant cardiac tissue function with a construct, or a construct associated with therapeutic cells, or a construct associated with fibroblast cells and therapeutic cells. 1. A method for treating a subject having a disorder or condition associated with aberrant cardiac tissue function , comprising contacting a patient having a disorder or condition associated with aberrant cardiac tissue function with a scaffold , wherein the scaffold is a substrate comprising a biocompatible , non-living material.2. The method of claim 1 , wherein the disorder or condition associated with aberrant cardiac tissue function is a cardiac arrhythmia.3. The method of claim 2 , wherein the cardiac arrhythmia is selected from the group consisting of tachycardia claim 2 , bradycardia claim 2 , ventricular tachycardia claim 2 , ventricular fibrillation claim 2 , arrhythmias generated from the upper chambers of the heart such as any supraventricular tacchycardia such as atrial fibrillation claim 2 , and diseases of the atrioventricular nodal tissue such as complete heart block.4. The method of claim 2 , wherein the cardiac arrhythmia is ventricular tachycardia.5. The method of claim 1 , wherein one or more therapeutic cell populations are associated with the scaffold.6. The method of claim 5 , wherein the one or more therapeutic cell populations are adhered to the heart.7. The method of claim 5 , wherein the one or more therapeutic cell populations are selected from mesoderm lineage cells such as fibroblasts claim 5 , cardiac cells claim 5 , or progenitors thereof claim 5 , or stem cells claim 5 , or cells derived from stem cells claim 5 , or multiple types ...

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Номер записи: 76

13-06-2019 дата публикации

Multipotential Expanded Mesenchymal Precursor Cell Progeny (MEMP) and Uses Thereof

Номер: US20190177685A1

Автор: Gronthos Stan, Zannettino Andrew Christopher William

Принадлежит: MESOBLAST, INC.

The invention relates to multipotential expanded mesenchymal precursor progeny (MEMP's), characterised by the early developmental markers STRO-1and ALP. The present invention also relates to methods for producing MEMP's and to uses of MEMP's for therapeutic applications. 155-. (canceled)56. A composition comprising a cultured or expanded cell population wherein at least 10% of the total cell population are expanded multipotential MPCs that have the phenotype STRO-1 , ALP and are also positive for one or more of the markers Ki67 , CD44 , CD49c/CD29 , VLA-3 or α3β1 , and wherein the composition further comprises STRO-1cells wherein the STRO-1cells are committed to a lineage of tissue or cell type selected from the group consisting of neural tissue , fat , cartilage , skeletal muscle , cardiac muscle , epithelial tissue , tendon , ligament , odnotoblast , pericyte , smooth muscle , glial tissue , vascular tissue , endothelial tissue , haematopoietic tissue , hepatic tissue and renal tissue.57. The composition of wherein at least 20% of the total cell population are expanded multipotential MPCs that have the phenotype STRO-1 claim 56 , ALP and are also positive for one or more of the markers Ki67 claim 56 , CD44 claim 56 , CD49c/CD29 claim 56 , VLA-3 or α3β1.58. The composition of wherein at least 50% of the total cell population are expanded multipotential MPCs that have the phenotype STRO-1 claim 56 , ALP and are also positive for one or more of the markers Ki67 claim 56 , CD44 claim 56 , CD49c/CD29 claim 56 , VLA-3 or α3β1.59. The composition of wherein the population comprises at least 5×10cells.60. The composition of wherein the population comprises at least 5×10cells.61. The composition of wherein the population comprises at least 5×10cells.62. The composition of wherein the population comprises at least 10cells.63. The composition of wherein the population comprises at least 10cells.64. The composition of wherein the population comprises at least 10cells.65. The ...

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Номер записи: 77

15-07-2021 дата публикации

COMPOSITE TISSUE-ENGINEERED INTERVERTEBRAL DISC WITH SELF-ASSEMBLED ANNULAR ALIGNMENT

Номер: US20210213168A1

Автор: Bonassar Lawrence J., Bowles Robert D., Gebhard Harry H., Hartl Roger

Принадлежит:

The present invention relates to a tissue-engineered intervertebral disc (IVD) suitable for total disc replacement in a mammal and methods of fabrication. The IVD comprises a nucleus pulposus structure comprising a first population of living cells that secrete a hydrophilic protein and an annulus fibrosis structure surrounding and in contact with the nucleus pulposus structure, the annulus fibrosis structure comprising a second population of living cells and type I collagen. The collagen fibrils in the annulus fibrosis structure are circumferentially aligned around the nucleus pulposus region due to cell-mediated contraction in the annulus fibrosis structure. Also disclosed are methods of fabricating tissue-engineered intervertebral discs. 1. (canceled)2. A tissue-engineered intervertebral disc (IVD) comprising:a nucleus pulposus structure comprising a first population of living cells andan annulus fibrosis structure surrounding and in contact with the nucleus pulposus structure, the annulus fibrosis structure comprising a second population of living cells and collagen, wherein collagen fibrils in the annulus fibrosis structure are circumferentially aligned around the nucleus pulposus structure due to cell-mediated contraction in the annulus fibrosis structure.3. The tissue-engineered IVD according to claim 2 , wherein the nucleus pulposus structure comprises an alginate gel.4. The tissue-engineered IVD according to claim 3 , wherein the alginate gel comprises about 0.5% to about 10% (w/v) alginate.5. The tissue-engineered IVD according to claim 2 , wherein the first population of cells are present in a concentration of about 1×10cells/ml to about 50×10cells/ml.6. The tissue-engineered IVD according to claim 2 , wherein the first population of cells secrete proteoglycan.7. The tissue-engineered IVD according to claim 2 , wherein the first population of cells comprise nucleus pulposus cells.8. The tissue-engineered IVD according to claim 7 , wherein the nucleus ...

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Номер записи: 78

15-07-2021 дата публикации

BIOMATERIALS FOR ENHANCED IMPLANT-HOST INTEGRATION

Номер: US20210213171A1

Автор: Baranski Jan D., BHATIA Sangeeta N., Chaturvedi Ritika, Chen Christopher S., STEVENS Kelly R., YANG Michael T.

Принадлежит:

The present disclosure provides patterned biomaterials having organized cords and extracellular matrix embedded in a 3D scaffold. According, the present disclosure provides compositions and applications for patterned biomaterials. Pre-patterning of these biomaterials can lead to enhanced integration of these materials into host organisms, providing a strategy for enhancing the viability of engineered tissues by promoting vascularization. 1. A method of making an ex vivo patterned biomaterial containing one or more endothelial cell cords , the method comprising:(a) organizing endothelial cells in micropatterns in a culture, thereby forming one or more endothelial cell cords from the endothelial cells; and,(b) at least partially embedding the one or more endothelial cell cords in a scaffolding, thereby forming an ex vivo patterned biomaterial containing one or more endothelial cell cords.2. The method of claim 1 , wherein organizing endothelial cells in micropatterns in a culture in step (a) comprises suspending cells in a liquid collagen.3. The method of claim 1 , wherein the scaffolding is a naturally-derived scaffolding.4. The method of claim 1 , wherein the scaffolding is a synthetic scaffolding.5. The method of claim 1 , wherein the scaffolding comprises collagen.6. The method of claim 1 , wherein the scaffolding comprises fibrin.7. The method of claim 1 , wherein the one or more endothelial cells cords are branched.8. The method of claim 1 , wherein the one or more endothelial cell cords are formed in a parallel arrangement with the scaffold.9. The method of claim 1 , wherein the one or more endothelial cell cords are formed in a nonparallel arrangement with the scaffold.10. The method of claim 1 , wherein the one or more endothelial cell cords are cylindrical claim 1 , Y-shaped or T-shaped.11. The method of claim 1 , wherein the one or more endothelial cells cords are solid or hollow in cross-section12. A method of promoting vascularization of an engineered ...

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Номер записи: 79

15-07-2021 дата публикации

SITU EXPANSION OF ENGINEERED DEVICES FOR REGENERATION

Номер: US20210213173A1

Автор: BHATIA Sangeeta N., Chen Christopher S., STEVENS Kelly R.

Принадлежит:

Engineered human tissue seed constructs are provided that are suitable for implantation in subjects. Methods of making and using the engineered tissue seed constructs are provided. 1. A method of in situ expansion of engineered tissue in a host , comprising:(a) providing an engineered tissue seed comprising:(i) one or more human endothelial cell cords; and(ii) one or more hepatocyte aggregates, wherein each hepatocyte aggregate comprises a first population of cells comprising human hepatocytes and a second population of cells comprising human stromal cells, wherein the one or more human endothelial cell cords and the one or more hepatocyte aggregates are each in a biocompatible scaffold; and(b) implanting the engineered tissue seed in the host at a site to allow the engineered tissue seed to expand in the host.2. The method of claim 1 , wherein the one or more human endothelial cell cords of (a)(i) are in a first biocompatible scaffold and the one or more hepatocyte aggregates of (a)(ii) are in a second biocompatible scaffold.3. The method of claim 2 , wherein the first biocompatible scaffold comprises collagen.4. The method of claim 2 , wherein the second biocompatible scaffold comprises fibrin.5. The method of claim 2 , wherein the first biocompatible scaffold comprises collagen and the second biocompatible scaffold comprises fibrin.6. The method of claim 1 , wherein the ratio of human hepatocytes to human stromal cells is 1:2 to 2:1.7. The method of claim 1 , wherein the engineered tissue seed expands 11-fold following implantation.8. The method of claim 1 , wherein the engineered tissue seed expands 50-fold following implantation.9. A method of in situ expansion of engineered tissue in a host claim 1 , comprising:(a) providing an engineered tissue seed comprising:(i) one or more human endothelial cell cords in a first biocompatible scaffold; and(ii) one or more hepatocyte aggregates, wherein each hepatocyte aggregate comprises a first population of cells ...

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Номер записи: 80

07-07-2016 дата публикации

A FLAP FOR DE-NOVO TISSUE REGENERATION

Номер: US20160193382A1

Автор: EGOZI Dana, KOFFLER Jacob, LEVENBERG Shulamit, SHANDALOV-LEVI Yulia

Принадлежит:

The present invention provides an implant which includes: (a) an autologous engineered tissue; and (b) a vasculature, wherein the engineered tissue is a porous scaffold embedded with endothelial cell, a fibroblast, a myoblast, a mesenchymal cell, an adipocyte, or any combination thereof, wherein the vasculature feeds the cells. Further, the invention provides a method for treating a subject afflicted with a large soft tissue defect by implanting the implant of the invention. 1. An implant comprising: (a) an engineered tissue; and (b) an autologous vasculature , wherein said engineered tissue comprises a porous scaffold embedded with cells comprising an endothelial cell , a fibroblast , a myoblast , a mesenchymal cell , an adipocyte , or any combination thereof , wherein said vasculature feeds said cells.2. The implant of claim 1 , wherein said engineered tissue comprises a porous scaffold embedded with: an endothelial cell and a cell expressing CD73and CD105.3. The implant of claim 2 , wherein said engineered tissue further comprises a myoblast.4. The implant of claim 1 , wherein said porous scaffold comprises poly-l-lactic acid (PLLA) and polylactic-co-glycolic-acid (PLGA).5. The implant of claim 1 , wherein said vasculature comprises an autologous vein and an autologous artery.6. The implant of claim 1 , wherein said implant is configured to repair a large soft tissue defect or a full-thickness abdominal wall defect.7. (canceled)8. The implant of claim 1 , wherein said porous scaffold comprises a diameter of 150 to 800 μm.9. (canceled)10. The implant of claim 1 , wherein said porous scaffold comprises at least 85% porosity.11. The implant of claim 1 , wherein said porous scaffold comprises fibrin claim 1 , fibronectin claim 1 , thrombin claim 1 , or any combination thereof.1221-. (canceled)22. A process for making an implant comprising: (a) an engineered tissue; and (b) an autologous vasculature claim 1 , wherein said engineered tissue comprises a porous scaffold ...

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Номер записи: 81

06-07-2017 дата публикации

CLICK-CROSSLINKED HYDROGELS AND METHODS OF USE

Номер: US20170189581A1

Автор: Desai Rajiv, Joshi Neel Satish, Koshy Sandeep T., Mooney David J., Stafford Alexander G.

Принадлежит:

The present disclosure provides click-crosslinked hydrogels and methods of use. 2. The hydrogel according to claim 1 , wherein:{'img': {'@id': 'CUSTOM-CHARACTER-00005', '@he': '3.22mm', '@wi': '6.01mm', '@file': 'US20170189581A1-20170706-P00001.TIF', '@alt': 'custom-character', '@img-content': 'character', '@img-format': 'tif'}, 'bond is a single bond;'}{'sup': 1', '2N, 'sub': 1', '6', '0', '3, 'Ris —C-Calkyl-NR—, or —C-Calkyl-C(O)—;'}{'sup': '2', 'sub': 1', '6', '1', '6', '1', '6', '1', '6, 'Ris a bond or aryl optionally substituted with halogen, hydroxy, C-Calkyl, C-Calkoxy, (C-Calkyl)amino, or di(C-Calkyl)amino;'}{'sup': 3', '2N, 'sub': 1', '6', '0', '3, 'Ris —C-Calkyl-NR—, or —C-Calkyl-C(O)—; and'}{'sup': '4', 'sub': 1', '6', '1', '6', '1', '6', '1', '6', '1', '6, 'Ris hydrogen, C-Calkyl, or heteroaryl, wherein heteroaryl is optionally substituted with halogen, hydroxy, C-Calkyl, C-Calkoxy, (C-Calkyl)amino, or di(C-Calkyl)amino.'}3. The hydrogel according to claim 2 , wherein Rand Rare both -methyl-NR—; or Rand Rare both —C(O)—.5. The hydrogel of claim 1 , wherein the first polymer and the second polymer are independently water-soluble polymers.6. The hydrogel of claim 1 , wherein the first polymer and the second polymer are the same polymer.7. The hydrogel of claim 1 , wherein the first polymer and the second polymer are independently selected from the group consisting of alginate claim 1 , chitosan claim 1 , polyethylene glycol (PEG) claim 1 , gelatin claim 1 , hyaluronic acid claim 1 , collagen claim 1 , chondroitin claim 1 , agarose claim 1 , polyacrylamide claim 1 , and heparin.8. The hydrogel of claim 1 , wherein the first polymer and the second polymer comprise a polysaccharide9. The hydrogel of claim 1 , wherein the first polymer and the second polymer are independently selected from group consisting of alginate claim 1 , chitosan claim 1 , and gelatin.10. The hydrogel of claim 9 , wherein the first polymer and the second polymer are independently ...

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Номер записи: 82

11-06-2020 дата публикации

Cell preparations for extemporaneous use, useful for healing and rejuvenation in vivo

Номер: US20200179456A1

Автор: Antoine Turzi, Donald DU TOIT

Принадлежит: Regenlab USA LLC

The present invention relates to new plasma or new platelet-rich plasma preparations, new cell dissociation methods, new cell associations or compositions, a method of preparation thereof, a use thereof, devices for the preparation thereof and preparations containing such a platelet-rich plasma preparation and cell associations or compositions. Specifically, the invention provides plasma or platelet-rich plasma alone or in cell composition preparations for use in tissue regeneration and bone regeneration and pain reduction.

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Номер записи: 83

22-07-2021 дата публикации

INDUCIBLE TISSUE CONSTRUCTS AND USES THEREOF

Номер: US20210222128A1

Автор: BHATIA Sangeeta N., CHEN Amanda, Chen Christopher S., CHHABRA Arnav, SONG Hyun Ho

Принадлежит:

Inducible engineered tissue constructs comprising at least one cell population comprising a genetic construct are provided. Methods of making and using said constructs are also provided. 1. An engineered tissue construct comprising one or more mammalian cell populations , wherein at least one cell population comprises a genetic construct comprising:(i) a polynucleotide encoding a polypeptide of interest comprising an inducible element, wherein the polypeptide is activated upon interaction of the inducible element with a biological molecule or small molecule; or(ii) a polynucleotide comprising an inducible promoter operably linked to a nucleotide sequence encoding a polypeptide or a nucleic acid molecule of interest, wherein expression of the polypeptide or nucleic acid molecule is controlled by the inducible promoter, wherein at least one cell population comprises parenchymal or non-parenchymal cells.2. The engineered tissue construct of claim 1 , wherein the polypeptide of interest of (i) or (ii) is a cell death-inducing polypeptide.39.-. (canceled)10. The engineered tissue construct of claim 1 , wherein the polypeptide of interest of (i) or (ii) induces cell proliferation in at least one cell population.1112.-. (canceled)13. The engineered tissue construct of claim 10 , wherein the polypeptide of interest is selected from the group consisting of Wnt2 claim 10 , epidermal growth factor (EGF) claim 10 , hepatocyte growth factor (HGF) claim 10 , fibroblast growth factor (FGF) claim 10 , vascular endothelial growth factor (VEGF) claim 10 , interleukin 8 (IL-8) claim 10 , angiotensin 2 (Ang-2) claim 10 , R-spondin-3 precursor (RSPO3) claim 10 , GATA-binding protein 4 (GATA4) claim 10 , interleukin 6 (IL-6) claim 10 , delta-like 4 (DLL4) claim 10 , inhibitor of DNA binding 1 (ID-1) claim 10 , prostaglandin E synthase 2 (PGE2) and colony stimulating factor 1 (CSF1).14. The engineered tissue construct of claim 1 , wherein the nucleic acid molecule of interest is an ...

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Номер записи: 84

20-07-2017 дата публикации

COMPOSITION, CELL STRUCTURE, PANCREATIC ISLET TRANSPLANTATION KIT, PANCREATIC ISLET CELL TRANSPLANTATION TREATMENT AGENT AND HYPOGLYCEMIC AGENT, COMPOSITION CONTAINING PANCREATIC ISLET, KIT CONTAINING PANCREATIC ISLET, AND PANCREATIC ISLET TRANSPLANTATION TREATMENT AGENT AND HYPOGLYCEMIC AGENT

Номер: US20170203005A1

Автор: IWAZAWA Reiko, Nakamura Kentaro

Принадлежит: FUJIFILM Corporation

An object of the present invention is to provide a composition containing a pancreatic islet, a cell structure containing a pancreatic islet or a pancreatic islet cell, a pancreatic islet transplantation kit, a pancreatic islet transplantation treatment agent, and a hypoglycemic agent which improve at least one of glucose sensitivity or blood sugar level-reducing performance after transplantation, and to provide a composition containing a pancreatic islet, a kit containing a pancreatic islet, a pancreatic islet cell transplantation treatment agent, and a hypoglycemic agent which can improve glucose sensitivity. According to the present invention, a composition including A: a cell structure which contains a biocompatible macromolecular block and at least one kind of cell and in which a plurality of the above-described macromolecular blocks are arranged in gaps between a plurality of the above-described cells; and B: a pancreatic islet, and a composition containing a pancreatic islet; and a spheroid formed of at least one type of stem cell are provided. 1. A composition comprising:A: a cell structure which contains a biocompatible macromolecular block and at least one kind of cell and in which a plurality of the macromolecular blocks are arranged in gaps between a plurality of the cells; andB: a pancreatic islet.2. The composition according to claim 1 ,wherein the thickness or the diameter of the cell structure is 100 μm to 3 cm.3. The composition according to claim 1 ,wherein the biocompatible macromolecular block is formed of a recombinant peptide.4. A cell structure comprising:a biocompatible macromolecular block;at least one kind of cell; anda pancreatic islet,wherein a plurality of the macromolecular blocks are arranged in gaps between a plurality of the cells.5. A cell structure comprising:a biocompatible macromolecular block; andat least two kinds of cells,wherein a plurality of the macromolecular blocks are arranged in gaps between a plurality of the cells, ...

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Номер записи: 85

28-07-2016 дата публикации

BIOMIMETIC HYBRID GEL COMPOSITIONS AND METHODS OF USE

Номер: US20160213817A1

Автор: "OBrien Timothy", BREKKE John H.

Принадлежит:

Disclosed herein are dry blends of polyanionic and polycationic macromolecules, solvating fluids serving as cell suspension fluids, hybrid gel compositions, and methods for treatment of patients with endocrine disorders by transplantation with such compositions. Hybrid gel compositions that promote a microenvironment suitable for cell viability and growth while maintaining a sufficient structural integrity for three-dimensional cell culture are also disclosed. 1. A hybrid gel composition comprising:dextran sulfate;at least one polycationic macromolecule; anda solvating fluid.2. The composition of claim 1 , further comprises hyaluronan.3. The composition of claim 2 , further comprising peptide fragments covalently bonded to hyaluronan.4. The composition of claim 1 , wherein the dextran sulfate is of a low molecular weight of about 5 kilodaltons to about 40 kilodaltons.5. The composition of claim 1 , wherein the composition has a Young's modulus of about 0.5 to about 60 kiloPascals.6. The composition of claim 1 , wherein the at least one polycationic macromolecule is chitosan.7. The composition of claim 6 , wherein the chitosan is deacetylated to at least 90%.8. The composition of claim 1 , further comprising embedded endocrine cells and embedded pluripotent cells claim 1 , wherein the embedded endocrine cells and embedded pluripotent cells are suspended in the solvating fluid.9. The composition of claim 1 , wherein the endocrine cells and the pluripotent cells are selected from the group consisting of pancreatic islet cells claim 1 , adrenal cells claim 1 , mesenchymal stem cells claim 1 , thyroid cells claim 1 , parathyroid cells claim 1 , parafollicular cells claim 1 , pinealocytes claim 1 , pituitary cells claim 1 , neurosecretory cells claim 1 , endocrine progenitor cells claim 1 , induced pluripotent stem cells claim 1 , and any combination thereof.10. The composition of claim 1 , wherein the dextran sulfate claim 1 , at least one polycationic macromolecule ...

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Номер записи: 86

05-08-2021 дата публикации

Artificial nerve conduit construction using tissue engineering methods

Номер: US20210236696A1

Автор: LU Naiyan, WENG Yuyan, YANG Guofeng, YU Xuejian, Zhang Xuan

Принадлежит:

The disclosure discloses a tissue-engineered nerve transplant and a preparation method thereof, and belongs to the technical fields of biomaterials and tissue engineering. By optimizing the specification of stripes, the stripes can independently induce EMSCs to differentiate to myelination cells (Schwann cells) to the maximum extent so as to obtain an EMSCs/biomaterial scaffold compound. The EMSCs/biomaterial scaffold compound can not only be used as a three-dimensional cell culture model for researching neural stem cell differentiation, nerve fiber growth and myelination molecular mechanisms in vitro, but also be used as a tissue engineering transplant for in-vivo transplantation to repair nervous system injury. In the disclosure, an EMSCs/micropatterned biomaterial film is rolled into a cylindrical multi-tunnel type nerve regeneration conduit to be used to repair sciatic nerve injury by transplantation, and results show that the disclosure can promote nerve regeneration and recovery of a lower limb motor function through injured portion transplantation, and has good clinical application prospects and research and development value. 1. A tissue-engineered nerve transplant , comprising a biomaterial that comprises a surface provided with a striped micropattern , the biomaterial is used as a scaffold , and the scaffold is inoculated with seed cells to form the tissue-engineered nerve transplant , and wherein the seed cells comprises ecto-mesenchymal stem cells (EMSCs).2. The tissue-engineered nerve transplant according to claim 1 , wherein the micropattern technology comprises photoetching claim 1 , electron beam lithography or nanoimprint lithography.3. The tissue-engineered nerve transplant according to claim 2 , wherein the striped micropattern has a width of 1-2 μm claim 2 , a spacing of 1-2 μm and a stripe height of 1-2 μm.4. The tissue-engineered nerve transplant according to claim 3 , wherein one or more of polydimethylsiloxane claim 3 , polycaprolactone claim ...

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Номер записи: 87

25-06-2020 дата публикации

DEVICE AND METHOD FOR MICROFLUIDICS-BASED 3D BIOPRINTING

Номер: US20200199514A1

Автор: Hauser Charlotte A.E., RAUF Sakandar

Принадлежит:

The present invention relates to a device and a method for building a 3D object by mixing a bioink solution, a buffer solution capable of inducing gelation of the bioink solution and a dispersion containing micro and/or nanoparticles, and ejecting the formed hydrogel out of a nozzle. The present invention further relates to a method of obtaining a hydrogel. 1. A device for printing a 3D object from a representation stored in a memory , the device comprising:a first inlet configured to take in a bioink solution, which is a peptide solution,a second inlet configured to take in a buffer solution capable of inducing gelation of the bioink solution,a third inlet configured to take in a dispersion,a fluid duct for mixing the bioink solution, the buffer solution and the dispersion to obtain a peptide hydrogel, anda nozzle configured to eject a peptide hydrogel to build the 3D object.2. The device of claim 1 , wherein the fluid duct comprises a first region for mixing the bioink solution and the dispersion to obtain a bioink-dispersion mixture and a second region for mixing the bioink-dispersion mixture with the buffer solution.3. The device of claim 1 , wherein the dispersion comprises a cell culture medium claim 1 , wherein the cell culture medium comprises a plurality of cell types.4. The device of claim 1 , wherein the dispersion comprises peptide nanoparticles claim 1 , silver nanoparticles claim 1 , gold nanoparticles claim 1 , nanowires claim 1 , quantum dots and/or carbon nanotubes.5. The device of claim 4 , wherein a plurality of cell types are encapsulated in the peptide microparticles and/or immobilized on a peptide microparticle surface.6. The device of claim 1 , further comprising a heating module configured to heat the fluid duct claim 1 ,and/or further comprising a micromixer.7. The device of claim 1 , further comprising one or more light emitters configured to irradiate the fluid duct.8. The device of claim 7 , wherein the light emitters comprise a first LED ...

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Номер записи: 88

04-08-2016 дата публикации

Middle ear mucosa-like cell sheet, process of producing the same and method of using the same

Номер: US20160220356A1

Автор: Hiromi Kojima, Hiroshi Moriyama, Masayuki Yamato, Takanori Hama, Teruo Okano

Принадлежит: Cellseed Inc, Jikei University, TOKYO WOMENS MEDICAL UNIVERSITY

The purpose of the present invention is to obtain an alternative to a substitute of the mucosa in the middle ear which is engrafted on the surface of the bone in the middle ear, hyperplasia of the granulation tissue and the bone and the development of the fibroblast cells in the middle ear are suppressed, and to obtain a middle ear mucosa-like cell sheet retaining cilia in the surface layer, comprising culturing nasal epithelium cells on a cell culture substrate coated with a polymer whose hydration force changes within a temperature range of 0 to 80° C., wherein the cells are cultured within a temperature range where the hydration force of the polymer is weak, and then changing the temperature to a temperature at which the hydration force is strong to recover the cultured cell sheet.

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Номер записи: 89

04-08-2016 дата публикации

NOVEL METHODS AND DEVICES TO STIMULATE THE FOLLICULAR NICHE USING ADIPOSE DERIVED REGENERATIVE CELLS AND ADIPOSE TISSUE

Номер: US20160220731A1

Автор: Conlan Bradford A., Daniels Eric

Принадлежит:

The present invention concerns a cell-enriched fat graft and methods of making and using the same. The present invention also provides a kit for making and using the cell-enriched fat graft of invention. 1. A method for hair growth , comprisingpreparing a cell-enriched fat graft, andinjecting into the subcutaneous space of an area of a subject in need thereof a cell-enriched fat graft to cause hair growth or cilia restoration or to prevent hair loss or cilia loss, wherein the cell-enriched fat graft comprisesa) adipose stem and regenerative cells (ADRCs) and a fat tissue, orb) a platelet rich plasma and a fat tissue.2. The method of claim 1 , wherein 1 gram of the cell-enriched fat graft comprises:ADRCs in a number ranging from about 10,000 cells to about 5 million cells, orthe platelet rich plasma in a volume ranging from 0.001 mL to 0.9 mL.3. The method of claim 1 , wherein the ADRCs and the fat tissue are provided in situ claim 1 , and the cell-enriched fat graft is generated by mixing in-situ an amount of the ADRCs and an amount of the fat tissue prior to use.4. The method of claim 3 , wherein the ADRCs are enzymatically extracted in situ from an adipose tissue claim 3 , and the fat tissue is cleaned in situ.5. The method of claim 4 , wherein the ADRCs are enzymatically extracted in situ and the fat tissue is collected and cleaned in situ from a liposuctioned tissue.6. The method of claim 1 , wherein the area of a subject is ear drum or intestine.7. The method of claim 1 , wherein preparing comprises:measuring the size of the area of the subject in need of hair growth or cilia restoration, determining a cell count in the cell-enriched fat graft,determining an amount of the cell-enriched fat graft of the cell count to generate effective hair growth or cilia restoration in the area.8. The method of claim 1 , wherein the subject is a human being.9. A kit for providing a cell-enriched fat graft in situ claim 1 , which kit comprisingan adipose stem and regenerative ...

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Номер записи: 90

09-08-2018 дата публикации

SCAFFOLD FOR GROWING NEURONAL CELLS AND TISSUE

Номер: US20180221415A1

Автор: BLUMENTHAL Jacob, LEVENBERG Shulamit

Принадлежит:

The present invention provides a composition based on poly-l-lactic acid (PLLA) acid polylactic-co-glycolic-acid (PLGA) scaffold on which neuronal tissue can ex-vivo grow. Further, more the invention provides a method for making cellular vasculature networks and a method for treating a neuronal injury in a subject, by implanting the current composition. 1. A method for treating a neuronal injury in a subject , comprising the step of implanting an ex-vivo vascularized implant in a site of neuronal injury , said ex-vivo vascularized implant comprises: a porous sponge comprising poly-l-lactic acid (PLLA) and polylactic-co-glycolic-acid (PLGA); olfactory bulb cells attached to the surface of said porous sponge and within said porous sponge; an endogenous nerve growth factor (NGF) de-novo produced by said olfactory bulb cells; and vasculature formed in-vitro within said porous sponge , thereby treating a neuronal injury in a subject.2. The method of claim 1 , wherein said olfactory bulb cells express the NGF receptor p75NTR.3. The method of claim 1 , wherein said olfactory bulb cells comprise fibroblasts claim 1 , astrocytes and olfactory ensheathing cells.4. The method of claim 1 , wherein said ex-vivo vascularized implant further comprises an endothelial cell claim 1 , a fibroblast claim 1 , or both.5. The method of claim 1 , wherein said ex-vivo vascularized implant further comprises fibronectin claim 1 , fibrin claim 1 , thrombin claim 1 , or any combination thereof.6. The method of claim 1 , wherein said ex-vivo vascularized implant further comprises brain-derived neurotrophic factor (BDNF) de-novo produced by said olfactory bulb cells.7. A method for making a neuronal ex-vivo vascularized implant claim 1 , comprising the step of co-culturing cells on a 3D scaffold in the presence of culture medium claim 1 , said cells comprises olfactory bulb cells and endothelial cells claim 1 , said 3D scaffold comprises poly-l-lactic acid (PLLA) and polylactic-co-glycolic-acid ( ...

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Номер записи: 91

25-08-2016 дата публикации

TISSUE ENGINEERED DEVICES AND METHODS FOR MAKING SAME

Номер: US20160243286A1

Автор: BOLAND Thomas, COLLINS Scott Forrest, YANEZ Maria

Принадлежит: The Board of Regents of the University of Texas Sy stem

Tissue engineered constructs and methods for fabricating the disclosed constructs are provided. Some of the disclosed tissue engineered constructs are designed to fill a void in the body due to surgical resection, for example from mastectomy or lumpectomy, wounds and the like. Some disclosed constructs comprise one or more projections designed to mimic the appearance of a structural feature when implanted into a host. 1. A volume forming unit (VFU) comprising adipocytes and at least one projection.2. The VFU of claim 1 , wherein the VFU further comprises endothelial channels.3. The VFU of claim 1 , wherein the at least one projection is designed to simulate at least one structural feature of a nipple.4. The VFU of claim 3 , wherein a second projection is designed to simulate the at least one structural feature of an areola and the second projection circumscribes the at least one projection designed to simulate at least one structural feature of a nipple.5. A method for creating a VFU claim 3 , comprising:adding (i) a mixture comprising at least one biocompatible hydrogel material and a multiplicity of cells to (ii) a negative mold;incubating the mold under conditions suitable for hydrogel formation, thereby creating the VFU.6. The method of claim 5 , wherein the cells comprise at least one of adipocytes claim 5 , endothelial cells claim 5 , fibroblasts claim 5 , or mesenchymal stem cells.7. The method of claim 5 , wherein the mixture comprising at least one biocompatible hydrogel material and a multiplicity of cells comprises at least two solutions that may be added to the mold simultaneously or in any order.8. The method of claim 5 , wherein at least one component of the mixture is added to the mold using bioprinting.95. The method of claim 5 , wherein the at least one biocompatible hydrogel material comprises at least one of fibrinogen claim 5 , a fibrinogen activator claim 5 , or thrombin.10. The method of claim 5 , wherein:(a) the cells comprise at least one of ...

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Номер записи: 92

06-11-2014 дата публикации

ENERGETIC THREE-DIMENSIONAL ARTIFICIAL CARDIAC PATCH AND USES THEREOF

Номер: US20140328806A1

Автор: Birla Ravi K.

Принадлежит: University of Houston

In some embodiments, the present disclosure provides a method for fabricating a three-dimensional artificial cardiac patch construct. In some embodiments, such method includes the steps of coating a substrate with an organic polymer; allowing the organic polymer coating to air dry; mounting anchors on the organic polymer coating; and sterilizing the organic polymer coating and the anchors. In further embodiments, the method includes the steps of forming a biodegradable gel-based support scaffold on top of the organic polymer coating and seeding the biodegradable gel-based support scaffold with neonatal cardiac cells. In yet further embodiments, the method comprises culturing the neonatal cardiac cells in vitro to form a real cardiac layer, under culture conditions that are suitable for the cells to self-organize into a monolayer and detach from the substrate to form the three-dimensional cardiac patch. In some embodiments, the present disclosure pertains to a method of treatment of cardiac tissue injury in a subject in need thereof. In some embodiments, the method includes implanting the three-dimensional artificial cardiac patch described above in the injured area of the subject. In another embodiment the present disclosure provides a composition comprising the three-dimensional artificial cardiac patch described above. Additional embodiments of the present disclosure pertain to a medicament including the three-dimensional artificial cardiac patch described above. 1. A method for fabricating a three-dimensional artificial cardiac patch construct comprising:coating a substrate with an organic polymer;allowing the organic polymer coating to air dry;mounting anchors on the organic polymer coating;sterilizing the organic polymer coating and the anchors;forming a biodegradable gel-based support scaffold on top of the organic polymer coating;seeding the biological support scaffold with neonatal cardiac cells; andculturing the neonatal cardiac cells in vitro to form a ...

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Номер записи: 93

23-08-2018 дата публикации

Multipotential Expanded Mesenchymal Precursor Cell Progeny (MEMP) and Uses Thereof

Номер: US20180237746A1

Автор: Gronthos Stan, Zannettino Andrew Christopher William

Принадлежит: MESOBLAST, INC.

The invention relates to multipotential expanded mesenchymal precursor progeny (MEMP's), characterised by the early developmental markers STRO-1and ALP. The present invention also relates to methods for producing MEMP's and to uses of MEMP's for therapeutic applications. 155-. (canceled)56. A composition comprising a cultured or expanded cell population wherein at least 10% of the total cell population are expanded multipotential MPCs that have the phenotype STRO-1 , ALP and are also positive for one or more of the markers Ki67 , CD44 , CD49c/CD29 , VLA-3 or α3β1 , and wherein the composition further comprises STRO-1cells wherein the STRO-1cells are committed to a lineage of tissue or cell type selected from the group consisting of neural tissue , fat , cartilage , skeletal muscle , cardiac muscle , epithelial tissue , tendon , ligament , odnotoblast , pericyte , smooth muscle , glial tissue , vascular tissue , endothelial tissue , haematopoietic tissue , hepatic tissue and renal tissue.57. The composition of wherein at least 20% of the total cell population are expanded multipotential MPCs that have the phenotype STRO-1 claim 56 , ALP and are also positive for one or more of the markers Ki67 claim 56 , CD44 claim 56 , CD49c/CD29 claim 56 , VLA-3 or α3β1.58. The composition of wherein at least 50% of the total cell population are expanded multipotential MPCs that have the phenotype STRO-1 claim 56 , ALP and are also positive for one or more of the markers Ki67 claim 56 , CD44 claim 56 , CD49c/CD29 claim 56 , VLA-3 or α3β1.59. The composition of wherein the population comprises at least 5×10cells.60. The composition of wherein the population comprises at least 5×10cells.61. The composition of wherein the population comprises at least 5×10cells.62. The composition of wherein the population comprises at least 10cells.63. The composition of wherein the population comprises at least 10cells.64. The composition of wherein the population comprises at least 10cells.65. The ...

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Номер записи: 94

09-09-2021 дата публикации

TISSUE USE FOR REPAIR OF INJURY

Номер: US20210275289A1

Автор: Dorn Brian, Shepard David, Tokish John

Принадлежит: Arthrex, Inc.

The present disclosure describes methods of treating an injury in a subject using placental tissue streamers, engineered tissue placental tissue hybrids, suture placental tissue hybrids, placental tissue patch hybrids, and tissue hybrids, and the use of these compositions to repair, treat, or support an injury or degenerative process in a subject. 1. A method of treating musculoskeletal tissue injury or degeneration in a subject comprising inserting at least one placental tissue streamer into an injured or degenerated tissue such that the placental tissue streamer is surrounded by the injured or degenerated tissue.2. The method of claim 1 , wherein the musculoskeletal injury or degeneration is a connective tissue injury or degeneration claim 1 , cartilaginous tissue injury or degeneration claim 1 , fibrous tissue injury or degeneration claim 1 , muscle tissue injury or degeneration claim 1 , or skeletal tissue injury or degeneration.3. The method of claim 1 , wherein the musculoskeletal injury or degeneration is to tendon claim 1 , cartilage claim 1 , ligament claim 1 , intervertebral disk claim 1 , or bone.4. The method of claim 1 , wherein the injured or degenerated tissue is a muscle of a rotator cuff or a tendon of a rotator cuff.5. The method of claim 1 , wherein the injured or degenerated tissue is a tear or partial thickness tear of a rotator cuff tendon.6. The method of claim 1 , wherein the at least one placental tissue streamer is attached to the injured or degenerated tissue.7. The method of claim 1 , wherein the at least one placental tissue streamer is inserted into the injured or degenerated tissue with a needle loaded with the at least one placental tissue streamer.8. The method of claim 1 , wherein the at least one placental tissue streamer is inserted into a supraspinatus tendon.9. The method of claim 8 , wherein at least one placental tissue streamer is attached to a supraspinatus muscle at one end and to a head of a humerous bone at the other end. ...

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Номер записи: 95

17-09-2015 дата публикации

Tissue transplant compositions and methods for use

Номер: US20150258145A1

Автор: John M. Garvey, Keith D. Crawford, Pamela Layton

Принадлежит: Brigham and Womens Hospital Inc, PARCELL LABORATORIES LLC

Provided are transplants and methods for augmenting formation and restoration of organ and tissue, for example, bone formation, by administering autologous or allogeneic human embryonic-like adult stem cells (ELA cells). Also provided is a method for augmenting formation of tissues and organs by administering a transplant having ELA stem cells or combination of ELA stem cells.

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Номер записи: 96

08-08-2019 дата публикации

METHODS AND DEVICES FOR CELLULAR TRANSPLANTATION

Номер: US20190240375A1

Автор: Hasilo Craig, Haworth Daniel Nicholas, Leushner Justin, Shohet Simon, Siroen Delfina Maria Mazzuca, Toleikis Philip Michael

Принадлежит:

Devices and methods for transplanting cells in a host body are described. The cell comprises a porous scaffold that allows ingrowth of vascular and connective tissues, a plug or plug system configured for placement within the porous scaffold, and a seal configured to enclose a proximal opening in the porous scaffold. The device may further comprise a cell delivery device for delivering cells into the porous scaffold. The method of cell transplantation comprises a two step process. The device is incubated in the host body to form a vascularized collagen matrix around a plug positioned within the porous scaffold. The plug is then retracted from the porous scaffold, and cells are delivered into the vascularized space created within the porous scaffold. 185-. (canceled)86. A method of treating diabetes in a patient in need thereof , comprising implanting a device in the patient , wherein a porous scaffold comprising an immunologically compatible polymer mesh forming the walls of at least one chamber;', 'wherein the chamber comprises an opening at either or both of a proximal end and a distal end of the chamber, wherein the proximal end and the distal end are separated by a lumen that is bounded by the walls, and wherein the porous scaffold has pores sized to facilitate growth of vascular and connective tissues around and through the walls of the at least one chamber;', 'at least one removable, non-porous plug configured to be positioned within the lumen of the at least one chamber,', 'wherein the plug extends along the lumen of the chamber; and', 'at least one seal configured to enclose either or both the proximal end and the distal end of the chamber;, 'the device comprisesmaintaining the device in the patient body until the device is infiltrated with vascular and connective tissues;accessing the implanted device;withdrawing the plug;infusing the chamber with cells, wherein at least some of the cells express insulin.87. The method according to claim 86 , further ...

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Номер записи: 97

30-07-2020 дата публикации

MULTIPHASIC TISSUE SCAFFOLD CONSTRUCTS

Номер: US20200237520A1

Автор: Bindra Randy, Ivanovski Saso, Lui Hei Man Hayman, Vaquette Cedryck

Принадлежит:

The present invention relates to a three-dimensional multiphasic synthetic tissue scaffold comprising first, second and third compartments, wherein: each said compartment comprises distinct microstructural, and/or chemical, and/or mechanical properties, and is connected with at least one other compartment of the scaffold via a continuous interface; the tissue scaffold is porous; and the external morphology of the tissue scaffold mimics that of a mammalian joint or a component thereof. The invention further relates to a method for producing the three dimensional multiphasic synthetic tissue scaffold using a polymeric material, the method comprising using a three-dimensional (3D) bioprinter to print the tissue scaffold by continuously deposit the polymeric material onto a platform until the tissue scaffold is produced in its entirety. 1. A three-dimensional multiphasic synthetic tissue scaffold comprising first , second and third compartments , wherein:each said compartment comprises distinct microstructural, and/or chemical, and/or mechanical properties, and is connected with at least one other compartment of the scaffold via a continuous interface;the tissue scaffold is porous; andthe external morphology of the tissue scaffold mimics that of a mammalian joint or a component thereof.2. The multiphasic synthetic tissue scaffold of claim 1 , wherein any one or more of the first claim 1 , second and/or third compartments comprises or consists of:a series of fibres; ora series of fibers comprising multiple fibre layers.3. (canceled)4. The multiphasic synthetic tissue scaffold of claim 1 , wherein the second compartment comprises a series of fibres mimicking the external morphology of a series of ligaments claim 1 , and said series of fibres are located intermediate to and connecting the first and third compartments.5. The multiphasic synthetic tissue scaffold of claim 4 , wherein:the multiple fibre layers comprise first and second fibre layers,the first fibre layer is ...

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Номер записи: 98

23-09-2021 дата публикации

SURFACE FUNCTIONALIZED IMPLANT AND METHOD OF GENERATING THE SAME

Номер: US20210290824A1

Автор: Engqvist Hakan, Maria de Peppo Giuseppe, Sladkova Martina

Принадлежит:

The present invention provides a method for functionalizing a medical implant surface to promote osseointegration upon implantation in bone tissue. 1. A method for functionalizing a surface of an implant to promote osseointegration upon implantation into bone tissue , comprising:a) seeding the surface of the implant with mesenchymal progenitor (MP) cells;b) culturing and expanding the cells to produce an extracellular matrix (ECM) on the surface; andc) decellularizing the surface, thereby functionalizing the surface of the implant.2. The method of claim 1 , wherein decellularizing removes cells from the surface while maintaining the ECM.3. The method of claim 2 , wherein decellularizing comprises incubating the surface in a treatment solution comprising water claim 2 , an alcohol claim 2 , or a nonionic surfactant.4. The method of claim 3 , wherein the treatment solution consists of deionized water.5. The method of claim 3 , wherein the treatment solution is a mixture of ethanol and water.7. The method of claim 6 , wherein the nonionic surfactant is polyethylene glycol tert-octylphenyl ether (Triton X-100™).8. The method of claim 3 , wherein the surface is incubated at 37° C. for about 30 to 60 minutes.9. The method of claim 1 , wherein decellularizing comprises freezing the surface in a physiological buffer.10. The method of claim 9 , wherein the physiological buffer is phosphate-buffered saline (PBS).11. The method of claim 9 , wherein the surface is frozen for greater than 30 minutes at −80° C. and subsequently thawed.12. The method of claim 1 , further comprising treating the surface with a nuclease after decellularizing.13. The method of claim 12 , wherein the surface is treated with a DNAse and an RNAse.14. The method of claim 12 , further comprising dehydrating the surface with successive applications of an ethanol-water solution claim 12 , in which each successively applied solution has a higher concentration of ethanol claim 12 , the final application being ...

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Номер записи: 99

06-09-2018 дата публикации

BIOMIMETIC HYBRID GEL COMPOSITIONS AND METHODS OF USE

Номер: US20180250443A1

Автор: "OBrien Timothy", BREKKE John H.

Принадлежит:

Disclosed herein are dry blends of polyanionic and polycationic macromolecules, solvating fluids serving as cell suspension fluids, hybrid gel compositions, and methods for treatment of patients with endocrine disorders by transplantation with such compositions. Hybrid gel compositions that promote a microenvironment suitable for cell viability and growth while maintaining a sufficient structural integrity for three-dimensional cell culture are also disclosed. 1. A method for forming a three-dimensional hybrid gel composition comprising:combining at least one anhydrous polyanionic macromolecule and a solvating fluid to form a composition; andadding at least one polycationic macromolecule to the composition to form the three-dimensional hybrid gel composition, wherein the three-dimensional hybrid gel composition contains a network of insoluble, polyelectrolytic complex structures that surround and penetrate regions of unreacted, homogeneous, dextran sulfate and other regions of unreacted, homogeneous polycationic macromolecules.2. The method of claim 1 , wherein the at least one anhydrous polyanionic macromolecule comprises dextran sulfate.3. The method of claim 1 , further comprising suspending in the solvating fluid cells selected from the group consisting of endocrine cells and pluripotent cells.4. The method of claim 3 , wherein the cells are selected from the group consisting of pancreatic islet cells claim 3 , adrenal cells claim 3 , mesenchymal stem cells claim 3 , thyroid cells claim 3 , parathyroid cells claim 3 , parafollicular cells claim 3 , pinealocytes claim 3 , pituitary cells claim 3 , neurosecretory cells claim 3 , endocrine progenitor cells claim 3 , induced pluripotent stem cells claim 3 , and any combination thereof.5. The method of claim 1 , further comprising adding hyaluronan.6. The method of claim 1 , further comprising adding peptide fragments covalently bonded to hyaluronan.7. The method of claim 1 , further comprising adding peptide ...

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Номер записи: 100

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