ACTIVE IMPLANTABLE MEDICAL DEVICE AND METHOD OF ITS USE

The present patent document claims the benefit of the filing date under 35 U.S.C. 119(e) to U.S. Provisional Patent Application No. 62/630,410US62630410, which was filed on February 14, 2018.

The present disclosure is directed generally to implantable medical devices and more particularly to implantable medical devices having power generation capabilities.

In medicine, stents may be inserted in a body lumen, vessel, or duct to keep the passageway open. For example, in aortic intervention, stents can address and correct issues resulting from atherosclerotic plaques, aneurysm or weakening of blood vessels, and arterial dissection. Currently, stents are passive devices that cannot use or generate energy to perform specific functions. Transforming stents and/or other implantable medical device from passive to active devices may open the door to new functions and/or improved efficacy.

US8241652US8241652B describes a method of controlling release rate of a bioactive agent from an implantable medical device comprising a coating, a coating on the implantable device and a method of making the coating.

US7326238US7326238B describes an apparatus and method to treat vulnerable plaque. In one embodiment, the apparatus has a medical device to treat an occlusive plaque, and is also adapted to release a biologically active agent to treat vulnerable plaque located downstream from the occlusive plaque. In an alternative embodiment, the apparatus has an expandable tube attached to the inner surface of a stent, and a layer of endothelial cells seeded on the inner surface of the expandable tube. The expandable tube shields a vulnerable plaque from a body lumen.

US2014/067040US2014067040A describes an implantable device having a power source. The power source uses reverse electrowetting technology to generate a charge to power the implantable device. The power source includes a flexible, nonconductive substrate having a first side and a second side opposite the first side with a channel between the first and second sides. Electrodes are arranged about the channel in a predefined pattern. A liquid is contained in the channel. The liquid includes a dielectric liquid and a conductive liquid that do not mix. The electric change is generated by moving the liquid back and forth across the electrodes. The force to pump or move the liquid is provided by organic means, such as, for example, the change in blood pressure between systolic and diastolic, the expansion and contraction of an organ, or the movement of a muscle.

WO2007/067794WO2007067794A describes An access catheter, comprising: a generally tubular member insertable through the skin into a body of a subject and including a proximal portion positionable proximate to the skin of the subject and a distal portion, the generally tubular member including a first tubular section comprising a polymer and at least about three percent by volume silver, wherein the first tubular section exhibits radiopacity and antimicrobial activity.

Abbas Abbaszadegan et all: "The effect of Charge at the Surface of Silver Nanoparticles on Antimicrobial Activity against Gram-Positive and Gram-Negative Bacteria: a Preliminary Study" describes that the bactericidal efficiency of various positively and negatively charged silver nanoparticles has been extensively evaluated in literature, but there is no report on efficacy of neutrally charged silver nanoparticles. The goal of the study was to evaluate the role of electrical charge at the surface of silver nanoparticles on antibacterial activity against a panel of microorganisms. Three different silver nanoparticles were synthesized by different methods, providing three different electrical surface charges (positive, neutral, and negative). The antibacterial activity of these nanoparticles was tested against gram-positive (i.e., Staphylococcus aureus, Streptococcus mutans, and Streptococcus pyogenes) and gram-negative (i.e., Escherichia coli and Proteus vulgaris) bacteria.

The invention is defined in the claims. An active implantable medical device comprises an expandable stent, a flexible cover material positioned on at least an outer surface of the expandable stent, a nanoscale source of electrical energy embedded within the cover material, where the nanoscale source of electrical energy is mechanically activatable to produce the electrical energy, and antimicrobial particles distributed on or within a surface region of the cover material. The antimicrobial particles are electrically connected to the nanoscale source of electrical energy. When the active implantable medical device is placed in a body vessel and exposed to pressure changes and/or mechanical stresses, mechanical activation of the nanoscale source occurs, thereby enabling production of the electrical energy and powering of the antimicrobial particles.

Also disclosed herein is method of using an active implantable medical device comprises inserting an active implantable medical device into a body vessel, where the active implantable medical device comprises: an expandable stent in a delivery configuration; a flexible cover material on at least an outer surface of the expandable stent; a nanoscale source of electrical energy embedded within the cover material, where the nanoscale source of electrical energy is mechanically activatable to produce the electrical energy; and antimicrobial particles distributed on or within a surface region of the cover material. The antimicrobial particles are electrically connected to the nanoscale source of electrical energy. The active implantable medical device is positioned at a treatment site in the body vessel, and the expandable stent is expanded from the delivery configuration to a deployed configuration, such that the active implantable medical device comes into contact with the body vessel. While the expandable stent is in the deployed configuration, the active implantable medical device is subjected to pressure changes and/or mechanical stresses within the body vessel, and the nanoscale source of electrical energy experiences frictional forces and/or deforms, thereby generating electrical energy to power the antimicrobial particles.

• FIG. 1A shows a perspective view of an active implantable medical device according to one embodiment, where the active implantable medical device includes an expandable stent with a flexible cover material positioned on an outer surface thereof. A nanoscale source of electrical energy is embedded in the flexible cover material, and antimicrobial particles are distributed on or within a surface region of the flexible cover material in electrical contact with the nanoscale source of electrical energy, as shown schematically in FIGs. 1B and 1C.
• FIG. 1B shows a longitudinal sectional view of part of the active implantable medical device shown in FIG. 1A.
• FIG. 1C shows a transverse cross-sectional view of the active implantable medical device shown in FIG. 1A.
• FIG. 2 shows a bundle of deformable fibers that may function as the nanoscale source of electrical energy in an active implantable medical device.
• FIG. 3 shows a fabric comprising deformable fibers or bundles of deformable fibers; the fabric may be embedded in the flexible cover material of an active implantable medical device.

FIGs. 1A-1C show an active implantable medical device 100 comprising an expandable stent 102 and a flexible cover material 104 positioned on an inner surface and/or an outer surface of the expandable stent 102. In other words, the flexible cover material 104 is positioned radially adjacent to the expandable stent 102, which has a generally tubular shape. A nanoscale source of electrical energy 106 is embedded within the cover material 104. The nanoscale source 106 can be mechanically activated to produce the electrical energy and thus may be described as being a mechanically-activatable nanoscale source 106. In one example, the nanoscale source of electrical energy 106 may utilize frictional forces to produce the electrical energy. In another example, the nanoscale source 106 may utilize mechanical stress (e.g., compressive, tensile, and/or shear stress) to produce the electrical energy, as discussed further below.

The active implantable medical device 100 further includes antimicrobial particles 108 distributed on or within a surface region 104a of the cover material 104. Suitable antimicrobial particles 108 may comprise silver, gold, copper, or another metal that exhibits antibacterial activity by destroying or preventing the growth of bacteria. For example, silver applied to the surface region 104a as a film (or embedded within the surface region 104a in particulate form) releases silver ions (Ag+) that have been shown to have biocidal effectiveness. The antimicrobial particles 108 are electrically connected to the nanoscale source of electrical energy 106. In one example, the active implantable medical device 100 may include a conductive layer or other conductive structure 110 between the surface region 104a and an interior portion 104b of the cover material to provide the electrical connection. When the active implantable medical device 100 is placed in a body vessel and exposed to pressure changes and/or applied stresses, mechanical activation of the nanoscale source 106 can occur, thereby enabling production of the electrical energy and powering of the antimicrobial particles 108. It has been recognized that electrical activation of the antimicrobial particles 108 can lead to an improvement in their bactericidal efficacy.

The antimicrobial particles 108 may take the form of discrete metal particles, agglomerated metal particles, and/or grains of a polycrystalline metal film (e.g., a polycrystalline silver film). The antimicrobial particles 108 may also or alternatively comprise metal particles dispersed in a polymer film, thereby forming a polymer composite on the surface region 104a. The polymer film may be electrically conductive, and may include poly(3,4-ethylenedioxythiophene) (PEDOT) or another conducting polymer. For example, poly(hydroxymethyl-3,4-ethylenedioxythiophene):polystyrene sulfonate (PEDOT-MeOH:PSS) has been shown to be a suitable conducting polymer for use with silver particles to form a polymer composite. The antimicrobial particles 108 may also or alternatively be stabilized with a suitable coupling agent, such as (3-aminopropyl)triethoxysilane (APTES).

It may be beneficial for the antimicrobial particles 108 to have a high surface area-to-volume ratio to promote release of the silver (or other metal) ions. Thus, the antimicrobial particles 108 may be antimicrobial nanoparticles having an average linear size (e.g., diameter or width) in a range from about 1 nm to about 500 nm, from about 2 nm to about 200 nm, or from about 5 nm to about 100 nm. As indicated above, the antimicrobial nanoparticles 108 may take the form of discrete metal nanoparticles, agglomerated metal nanoparticles, or grains of a nanocrystalline metal film. The antimicrobial nanoparticles may be surface-stabilized as described above and may also or alternatively be distributed in a polymer film, thereby forming a polymer nanocomposite.

The nanoscale source of electrical energy 106 may comprise a plurality of deformable fibers 112 distributed within the cover material 104. Advantageously, the deformable fibers 112 may be distributed in bundles 114, as illustrated in FIG. 2, where each bundle comprises two or more deformable fibers in a twisted arrangement that may promote frictional contact during use. In one example, a fabric 116 that includes the deformable fibers 112 (or bundles 114 of the deformable fibers 112) in a woven arrangement, as shown in FIG. 3, may be embedded within the cover material 104. The deformable fibers 112 may have nanoscale dimensions, such as a width or diameter in a range from about 1 nm to about 500 nm. The length of the deformable fibers 112 may be much larger than the width or diameter.

The nanoscale source of electrical energy 106 (e.g., the deformable fibers 112) may comprise a piezoelectric material and/or a triboelectric material, where a piezoelectric material may be understood to be a material that generates electrical charge when subjected to a mechanical stress (thereby exhibiting the piezoelectric effect), and a triboelectric material may be understood to be a material that generates electrical charge when subjected to frictional contact (thereby exhibiting the triboelectric effect).

Suitable piezoelectric materials for the nanoscale source of electrical energy 106 may include, for example, carbon (e.g., graphene, graphite, carbon nanotubes), boron nitride, quartz, barium titanate, zinc oxide, lead zirconate titanate (PZT), bismuth titanate, sodium bismuth titanate, bismuth ferrite, potassium niobate, sodium niobate, sodium potassium niobate, sodium tungstate, zinc oxide, aluminum nitride, gallium nitride, indium nitride, and polyvinylidene fluoride. Suitable triboelectric materials for the nanoscale source 106 may include, for example, carbon (e.g., graphene, graphite, carbon nanotubes), nylon, aluminum, lead, nickel, copper, silver, gold, platinum, and silicon. The nanoscale source of electrical energy 106 may comprise a material that exhibits both the piezoelectric effect and the triboelectric effect.

When implanted within a body vessel, the medical device 100 is subjected to pressure changes in the vessel as well as to mechanical stresses from expansion, contraction, and/or bending of the vessel wall. Consequently, in use, the deformable fibers 112 or other nanoscale source of electrical energy 106 may deform and experience frictional forces due to abrasive contact with adjacent fibers 112 and/or the cover material 104, thereby generating electrical energy.

The flexible cover material 104 may comprise a polymer, such as a thermoplastic polyurethane, polyamide, polysiloxane (e.g., polydimethylsiloxane (PDMS)), polyolefin, polyethylene, polyethylene terephthalate (PET), or polytetrafluoroethylene (PTFE). The flexible cover material 104 may be electrically insulating and is preferably biocompatible. In some embodiments, the cover material 104 may include two or more layers (i.e., a plurality of layers), and the nanoscale source of electrical energy 106 may be embedded between adjacent layers.

It may be beneficial to store some or all of the electrical energy produced by mechanical activation of the nanoscale source 106. Thus, one or more supercapacitors 118 may be embedded within the cover material for charge storage. Each supercapacitor 118 may be electrically connected to the nanoscale source of electrical energy 106 and to the antimicrobial particles 108. In one example, the supercapacitor 118 may be fabricated from graphene ribbons, as described for example in Chen, et al. "Graphene-based fibers for supercapacitor applications," Nanotechnology, 27, 3 (2015). In another example, the supercapacitor 118 may include MnO₂ nanowires as described in Lv, et al. "Editable Supercapacitors with Customized Stretchability Based on Mechanically Strengthened Ultralong MnO2 Nanowire Composite," Adv. Mater. 30, 1704531 (2018). Such MnO₂ nanowires can be stretched up to 500% and are editable into different shapes and structures.

The expandable stent 102 may comprise a metal frame that is fabricated from stainless steel, a cobalt-chrome alloy, a nickel-titanium alloy, or another biocompatible alloy. The expandable stent may be self-expanding or balloon-expandable.

The active insertable medical device 100 may be fabricated using methods known in the art. The fabrication of expandable stents 102 is well known, and may entail, for example, laser machining of a metal alloy cannula or bending a number of metal alloy wires about a mandrel to obtain the desired stent geometry (e.g., a mesh or zigzag structure). Self-expanding stents formed of nickel-titanium alloys may further require a heat setting step, as known in the art, in order to impart to the stent a remembered shape and the superelastic properties required for self-expansion in the body vessel. After fabricating the stent and prior to applying the cover material, the stent may be polished (e.g., electropolished), cleaned, and/or primed as is known in the art.

The cover material 104 may be applied to the expandable stent 102 by spraying, dipping, painting, or otherwise depositing a cover material precursor, followed by drying or curing. Multiple layers may be achieved by successive passes of depositing and drying/curing. The nanoscale source of electrical energy (e.g., deformable fibers) 106 may be applied to the medical device 100 between passes in order to embed the nanoscale source 104 in the cover material 104. The conductive layer or structure(s) 110, when present, and any supercapacitors 118 may be embedded in the cover material 104 in the same way. Generally, the cover material 104 has a thickness ranging from about 0.0025 mm to about 2.5 mm. The cover material 104 may overlie both inner and outer surfaces of the stent 102, optionally covering any cells or interstices defined by the stent geometry. If desired, the cover material 104 may be selectively applied to just the outer surface of the expandable stent 102, as shown in FIGs. 1A-1C. Finally, the antimicrobial particles may be applied to or embedded in the surface region 104a of the cover material 104 in the form of discrete metal particles, agglomerated metal particles, a polymer composite including metal particles, or a polycrystalline metal film having any of the characteristics described above, such as a nanoscale particle or grain size.

To utilize the active implantable medical device 100, the expandable stent 102 may be compressed to a delivery (unexpanded) configuration and inserted into a body vessel for positioning at a treatment site. Once at the treatment site, the stent 102 may be expanded to a deployed configuration such that the medical device 100 (and in particular the antimicrobial particles at the surface region 104a) come into contact with the vessel wall. In the deployed configuration, the medical device 100 is subjected to pressure changes in the vessel as well as mechanical stress due to expansion, contraction, and/or bending of the vessel wall. Consequently, the nanoscale source of electrical energy 106 may deform and/or experience frictional forces, thereby generating electrical energy to power the antimicrobial particles while the stent 102 is deployed.

While various embodiments have been described, it will be apparent to those of ordinary skill in the art that many more embodiments and implementations are possible. Accordingly, the embodiments described herein are examples, not the only possible embodiments and implementations.

Furthermore, the advantages described above are not necessarily the only advantages, and it is not necessarily expected that all of the described advantages will be achieved with every embodiment.