Abstract: Implantable or insertable medical devices are provided, which comprises: (a) a biocompatible polymer; and (b) at least one therapeutic agent selected from an anti-inflammatory agent, an analgesic agent, an anesthetic agent, and an antispasmodic agent. The medical devices are adapted for implantation or insertion at a site associated with pain or discomfort upon implantation or insertion. In many embodiments, the therapeutic will be selected from at least one of (i) ketorolac and pharmaceutically acceptable salts thereof (e.g., ketorolac tromethamine) and (ii) 4-diethylamino-2-butynylphenylcyclohexyl glycolate and pharmaceutically acceptable salts thereof (e.g., oxybutynin chloride). Also provided are uses for the implantable or insertable medical devices, which uses comprise reducing pain or discomfort accompanying the implantation or insertion of such devices. Further uses may comprise reducing microbial buildup along the device.

Abstract: Biodegradable polymers formed from biodegradable polyester-based prepolymers, to which ring-structured anhydrides which have different hydrophobicities have been connected, and which are either coupled to form linear thermoplastic polyester anhydrides or cross-linked to form network-structured polyester anhydrides. It is possible to adjust widely the degradation rate and mechanism of the polymers and thus they can be used, for example, in the controlled dosing of pharmaceutical ingredients, for tissue technological applications, in surgery and in bioactive composites.

Abstract: Coatings for medical devices, methods of making the coatings, and methods of using them are described.

Abstract: The invention includes a medical hydrogel made from polymerized polysaccharide macromers. The macromers are preferably polysaccharides decorated with polymerizable groups, for example, methacrylates. The macromers may also be made into polymers of at least two macromers polymerized together. These polymers are preferably multi-armed or high-molecular weight and used for medical uses, for example, making coatings on medical devices. Macromers of N-vinylpyrrolidone are also disclosed herein.

Abstract: Implantable medical devices employing a sol-gel composition coatings that functions as a bioactive material reservoir, and the use of sol-gel composition coatings for improved adhesion of organic and inorganic substrates are disclosed.

Abstract: Provided herein are skin substitutes suitable for use in a living subject for purpose of repairing damaged tissues, methods of producing the skin substitutes and their uses. A biocomposite membrane comprising poly(?-caprolactone) (PCL) and at least one material selected from collagen and gelatin is provided. In one embodiment, the biocomposite is a 2-component membrane of PCL and gelatin. In another embodiment, the biocomposite is a 3-component membrane of PCL, collagen and gelatin. The bio-composite membrane may be used directly in vivo as a wound dressing, or as a support for cell growth on each side of the membrane to produce an in vitro cultivated artificial skin for future in vivo and/or in vitro applications.

Abstract: A process for producing a lactic acid polymer of 15,000 to 50,000 in weight-average molecular weight, the content of polymeric materials having not more than about 5,000 in weight-average molecular weight therein being not more than about 5% by weight, characterized by hydrolyzing a high molecular weight lactic acid polymer, placing the resultant solution comprising the hydrolyzed product under a condition capable of precipitating the objective lactic acid polymer, separating the precipitated lactic acid polymer and collecting them. The lactic acid polymer is useful as a matrix for sustained-release preparations. The sustained-release microcapsule preparation encapsulating a physiologically active substance can fully prevent the initial excessive release of the physiologically active substance from the microcapsules and keep a stable release rate over a long period of time.

Abstract: An antibiotic coating of implants is described, which is characterized in that the coating comprises at least one saturated, organic, hydrophobic, low molecular matrix former whose melting point is in the temperature range of 45° C. to 100° C., in which a low molecular, hydrophobic additive is dissolved and that an antibiotic/antibiotics is/are suspended in the mixture of matrix former and additive and/or in which an antibiotic/antibiotics miscible with a mixture of matrix former and additive is/are dissolved.

Abstract: The invention relates to methods and compositions for treating skin aging, said compositions comprising at least one tropoelastin promoter and at least one tropoelastin crosslinker.

Abstract: A material and method for augmenting soft tissue. The tissue augmentation material consists essentially of water and a polysaccharide gel former selected from the group consisting of a cellulose polysaccharide, starch, chitin, chitosan, hyaluronic acid, hydrophobe modified polysaccharide, an alginate, a carrageenan, agar, agarose, an intramolecular complex of a polysaccharide, an oligosaccharide and a macrocylic polysaccharide. Glycerin may also be included. The material may be used to augment soft tissue in a variety of areas, including the facial region and vocal folds.

Abstract: According to an aspect of the present invention, implantable or insertable medical devices are provided, which contain polymeric release regions that control the release of one or more therapeutic agents. The polymeric release regions, in turn, contain one or more polymers that contain one or more rigid, nonplanar polycyclic molecular structures. The therapeutic agent is disposed beneath or within the polymeric release region.

Abstract: The present invention is directed to a stabilized cross-linked hydrogel matrix comprising a first high molecular weight component and a second high molecular weight component that are covalently linked, and at least one stabilizing or enhancing agent, wherein the first high molecular weight component and the second high molecular weight component are each selected from the group consisting of polyglycans and polypeptides. This stabilized hydrogel matrix may be prepared as bioactive gels, pastes, slurries, cell attachment scaffolds for implantable medical devices, and casting or binding materials suitable for the construction of medical devices. The intrinsic bioactivity of the hydrogel matrix makes it useful as a gel or paste in multiple applications, including as a cell attachment scaffold that promotes wound healing around an implanted device, as gels and pastes for induction of localized vasculogenesis, wound healing, tissue repair, and regeneration, as a wound adhesive, and for tissue bulking.

Abstract: One embodiment of the invention relates to a medical implant whose surface is completely or partially covered by a coating composed of at least one active substance or containing at least one active substance.

Abstract: Apparatus is provided, including a plurality of islets, and a hydrogel configured to macroencapsulate the plurality of islets. The hydrogel is implantable in a subcapsular space (21) of a kidney (22) of a subject and is shaped to define a planar configuration. Other applications are also described.

Abstract: One embodiment of an anti-thrombogenic device includes a substrate, an attachment compound including a first end directly, mechanically secured to the substrate a second end positioned opposite the substrate, and an anti-thrombogenic species bonded to the second end of the attachment compound.

Abstract: A biocompatible polymeric controlled release matrix for delivery of one or more bioactive agents from an implantable medical device is described. In one embodiment, the polymeric controlled release matrix is a complaint film that includes one or more compliant biocompatible polymers and one or more bioactive agents. In another embodiment, the polymeric controlled release matrix is an elastomeric collar that includes one or more elastomeric biocompatible polymers and one or more bioactive agents.

Abstract: The present invention provides a method for the formation of a medical device that comprises a therapeutic agent and a release region, which regulates the rate at which the therapeutic agent is released from the medical device. The method comprises providing a precursor region that comprises a polymer composition comprising two or more microphase separated polymer domains that are immiscible with one another, and forming said release region by a process that comprises applying an orienting field comprising an electric field, a magnetic field, a mechanical shear field, or a solvent gradient field, or a combination of two or more fields to said precursor region, wherein said field or combination of fields changes the spatial orientation of the microphase separated polymer domains within the release region. The electric, magnetic, mechanical shear or solvent gradient field is of sufficient strength to change the spatial orientation of the microphase separated domains.

Abstract: Therapeutic compositions, devices and protocols for the treatment of keloids and other abnormal scars with improved appearance and a much lower recurrence rate. A therapeutic drug delivery device comprises an injectable mixture of a fibroblast inhibitor such as corticosteroid and a slow release carrier such as milled gel sponge dispersed in a fluid medium such as biological saline. The composition can be injected perilesionally in the dermis following excision of the keloid or other scar tissue, to circumscribe the wound. The infiltration of the mixture around the wound can provide a slow release of the fibroblast inhibitor for an extended period of time until normal wound closure can dominate and keloid or abnormal scar recurrence is inhibited.

Abstract: The present invention relates to microarray polymeric barriers designed to control the release rate of therapeutic agents. By varying the thickness of the coating or affecting, physically and/or chemically, the constituents of the barrier composition, the release profile of the underlying therapeutic agent can be modified and controlled.

Abstract: Coatings are provided in which surfaces may be activated by covalently bonding a combination ofsilane derivatives (A) to the metal surface, covalently bonding a lactone polymer (B) to the silane derivative by in situ ring opening polymerization, and depositing at least one layer of a polyester (C) on the bonded lactone polymer. Biologically active agents or therapeutic compounds may be deposited with any of the polyester layers. Such coated surfaces may be useful in medical devices, in particular stents.

Abstract: The invention relates to a method for differentially representing myocardial tissue in different states of damage, comprising the following steps: administering a myocardium-suitable contrast agent to a patient under examination; entering at least one patient-specific parameter affecting the speed of uptake by and elimination from the myocardium of said contrast agent; calculating a point in time after administration of the contrast agent at which a difference between a contrast agent content in necrotic myocardial tissue and a contrast agent content in non-necrotic myocardial tissue attains a maximum value, on the basis of the at least one patient-specific parameter, and carrying out, at the point in time calculated, a late-phase CT scan for accentuation of necrotic myocardial tissue compared to non-necrotic myocardial tissue. The invention likewise relates to apparatus, in particular for carrying out the method.

Abstract: A medical device with a therapeutic agent-releasing polymer coating. The medical device is provided by a method that comprises: (a) attaching at least one reactive species to a medical device surface, which reactive species leads to chain growth polymerization in the presence of monomer; (b) contacting the reactive species with at least one monomer species, thereby forming a polymer coating on the surface of the medical device; and (c) providing at least one therapeutic agent within the polymer coating. The therapeutic agent may be incorporated during formation of the polymer coating or after formation of the polymer coating. The at least one reactive species can comprise, for example, a free radical species, a carbanion species, a carbocation species, a Ziegler-Natta polymerization complex, a metallocene complex, and/or an atom transfer radical polymerization initiator.

Abstract: The present invention relates to the design and composition of a depot implant for optimal delivery of growth factors to treat bone avascular necrosis, in that such depot implant is constructed to be in a cylinder (rod) or sphere shape and have a natural or synthetic polymer scaffold with or without impregnated calcium phosphate particles. The density of the depot is higher than a typical BMP sponge carrier to facilitate its implantation and slower release of the growth factor. The scaffold is such that it has adequate porosity and pore size to facilitate growth factor seeding and diffusion throughout the whole of the bone structure resulting in increased new blood vessel growth and density in the avascular necrotic bone. In addition, the shape of the depot implant allows for delivery through a cannula or large bore needle.

Abstract: Medical implants formed of hydrophobic derivatives of natural biodegradable polysaccharides and that include bioactive agent are described. The implants demonstrate desirable bioactive agent release profiles and can be prepared to have high drug loading. The implants can be used to treat medical conditions, such as those requiring prolonged administration of the bioactive agent at a target location in the body.

Abstract: According to one aspect, implantable or insertable medical devices are provided, which contain polymeric release regions that release one or more therapeutic agents. The polymeric release regions, in turn, contain the following: (i) a first bonding polymer having a first polymer block and a first bonding group and (ii) a second bonding polymer having a second polymer block and a second bonding group. A therapeutic agent is disposed beneath or within the polymeric release region. The first and second polymer blocks can be the same as or different from one another, as can the first and second bonding groups. The first and second bonding groups are bound to one another via non-covalent bonding, for example, via electrostatic interaction, coordinative bonds, ?-? stacking, or hydrogen bonding.

Abstract: Biocompatible intraocular implants include a retinoid component and a biodegradable polymer that is effective to facilitate release of the retinoid component into an eye for an extended period of time. The therapeutic agents of the implants may be associated with a biodegradable polymer matrix, such as a matrix that is substantially free of a polyvinyl alcohol. The implants may be placed in an eye to treat or reduce the occurrence of one or more ocular conditions, such as retinal damage, including glaucoma and proliferative vitreoretinopathy.

Abstract: The present invention relates to methods for in situ treatment of malignant cells from a cancer associated with bone. In one method, the treatment is for a primary cancer and entails positioning an implant containing and/or coated with at least one active agent for treating malignant cells directly in/on or indirectly among/near (e.g., by placing the implant in an area immediately proximal to) a site containing the malignant cells. In another method, the treatment includes positioning an implant containing and/or coated with at least one active agent for treating malignant cells directly in/on or indirectly among/near (e.g., by placing the implant in an area immediately proximal to) a surgical site from which malignant cells were previously removed/excised.

Abstract: Described herein are methods and compositions related to biologic matrices comprising at least one anti-infective. In certain embodiments, the invention relates to a biologic matrix comprising a slowed release anti-infective agent. In a particular embodiment, the invention relates to an acellular dermal matrix comprising a slowed release antiinfective agent, wherein the anti-infective agent is triclosan. In further embodiments, the the biologic matrix is suitable for use in surgical procedures, such as, for example, for the replacement of damaged or inadequate integumental tissue or for the repair, reinforcement or supplemental support of soft tissue defects.

Abstract: The present invention relates to a controlled release pharmaceutical delivery device which provides sustained or pulsatile delivery of a selected pharmaceutically active substance for a predetermined period of time. The device comprises about 1 to 80% by weight covalently crosslinked water insoluble, water-swellable polymers and about 1 to 75% by weight uncrosslinked, linear water soluble polymers. The invention also provides pharmaceutical compositions and methods for making such compositions in which a pharmaceutically active agent is incorporated into the delivery device.

Abstract: Compositions for nucleus pulposus regeneration is provided. Such composition may comprise a scaffolding material and a pore creating agent dispersed within the scaffolding material. The pore creating agent is removed from the scaffolding material in vivo, after the composition is administered to a patient. The pore creating agent may include an active agent, such as a growth factor, which may be released as the pore creating agent is being gradually removed from the scaffolding material. In addition, removal of the pore creating agent results in a porous scaffold for cells capable of regeneration of nucleus pulposus, either existing in situ or delivered separately, to attach to for further proliferation and regeneration.

Abstract: The common premise of synthetic implants in the restoration of diseased tissues and organs is to use inert and solid materials. Here, a porous titanium implant enables the delivery of microencapsulated bioactive cues. Control-released TGF?1 promoted the proliferation and migration of human mesenchymal stem cells into porous implants in vitro. Upon 4-wk implantation in the rabbit humerus, control-released TGF?1 from porous implants significantly increased BIC by 96% and bone ingrowth by 50% over placebos. Control-released 100 ng TGF?1 induced equivalent BIC and bone ingrowth to adsorbed 1 ?g TGF?1, suggesting that controlled release is effective at 10-fold less drug dose than adsorption. Histomorphometry, SEM and ?T showed that control-released TGF?1 enhanced bone ingrowth in the implant's pores and surface. These findings suggest that solid prostheses can be transformed into porous implants to serve as drug delivery carriers, from which control-released bioactive cues augment host tissue integration.

Abstract: A coating for a medical device, particularly for a drug eluting stent, is described. The coating can include a polymer having in a dry state a glass transition temperature within a range of between about 20° C. and about 55° C.

Abstract: A biointerface membrane for an implantable device including a nonresorbable solid portion with a plurality of interconnected cavities therein adapted to support tissue ingrowth in vivo, and a bioactive agent incorporated into the biointerface membrane and adapted to modify the tissue response is provided. The bioactive agents can be chosen to induce vascularization and/or prevent barrier cell layer formation in vivo, and are advantageous when used with implantable devices wherein solutes are transported across the device-tissue interface.

Abstract: A retrievable, sustained release, solid dosage form is provided for implanting into cranial bony canals and for prolonged release of an anesthetic, whereby treating neurovascular conditions, such as migraine. The dosage comprises an anesthetic contained in a polymeric carrier, and a retrieval member, the anesthetic being gradually released from the carrier.

Abstract: The present disclosure relates to dressings, such as patches and bandages, and other devices and systems that deliver nitric oxide.

Abstract: A tissue engineering composition adapted for application to an interior surface of a body lumen of a patient. The composition comprises (a) a carrier medium that is adapted to flow and to stably adhere the composition to the body lumen and (b) microcapsules, which are dispersed within the carrier medium and which contain one or more living cells encapsulated within a coating that includes a biodegradable polymer. The composition promotes growth of the cells on the lumen surface subsequent to application of the composition to the lumen.

Abstract: Disclosed herein is a matrix for inducing or enhancing osteoclast differentiation. The matrix comprises a material having an osteoclastogenic agent associated therewith, the agent being releasable from the material in an amount which is sufficient to induce or enhance osteoclast differentiation.

Abstract: A cosmetic material, cell growth promoting agent, elastase activity inhibiting agent and anti-aging agent containing sweet pea extract, formulated with the aim of preventing or slowing aging.

Abstract: This invention relates to devices and methods for the local, differential delivery of nitric oxide within the body. The devices include devices having at least two differing nitric oxide donor compounds, such as nitric oxide donor compounds having differing half-lives and nitric oxide donor compounds having different release mechanisms. The devices also include devices having at least two chemically distinct compositions to which nitric oxide donor compounds are adsorbed or attached or within which the donor compounds are disposed. The devices are typically used to increase local nitric oxide concentration in the body upon placement of the medical article at a delivery position on or within a patient.

Abstract: The present invention is directed to a stabilized cross-linked hydrogel matrix comprising a first high molecular weight component and a second high molecular weight component that are covalently linked, and at least one stabilizing or enhancing agent, wherein the first high molecular weight component and the second high molecular weight component are each selected from the group consisting of polyglycans and polypeptides. This stabilized hydrogel matrix may be prepared as bioactive gels, pastes, slurries, cell attachment scaffolds for implantable medical devices, and casting or binding materials suitable for the construction of medical devices. The intrinsic bioactivity of the hydrogel matrix makes it useful as a gel or paste in multiple applications, including as a cell attachment scaffold that promotes wound healing around an implanted device, as gels and pastes for induction of localized vasculogenesis, wound healing, tissue repair, and regeneration, as a wound adhesive, and for tissue bulking.

Abstract: An implantable matrix is provided, the matrix having a porous interior configured to release a growth factor and to allow influx of at least progenitor, bone and/or cartilage cells therein; and a biodegradable membrane disposed on the porous interior, the biodegradable membrane being less porous than the porous interior and configured to retain the growth factor and release the growth factor from the porous interior as the biodegradable membrane degrades at or near the target tissue site. In some embodiments, a method for making the implantable collagen matrix is provided, the method comprising: providing a porous collagen layer configured to release a growth factor and to allow influx of at least progenitor, bone and/or cartilage cells therein, and disposing a collagen membrane on the porous collagen layer, the collagen membrane being less porous than the porous collagen layer and configured to retain the growth factor.

Abstract: A method of improving bioavailability of ergot derivatives administered using sustained-release delivery systems includes combining an ergot derivative or mixture thereof with a pharmaceutically acceptable hydrophilic swelling agent or mixture thereof and one or more pharmaceutically acceptable excipients. The bioavailability of sustained-release formulations of the present invention is at least equal to the bioavailability of the ergot derivative or mixture thereof administered using a conventional delivery system. Sustained-release compositions that improve bioavailability are also provided. Methods and compositions according to the present invention may provide sustained-release characteristics while improving the bioavailability of ergot derivatives.

Abstract: This invention is directed to an apparatus and method for producing microparticles comprising pharmacologically active agents and biodegradable polymers. The apparatus includes a spinning disk containing a reservoir in the center thereof and a flat inclined surface. The apparatus optionally includes serrations and/or a flat surface beneath the periphery of the disk that is parallel to the rotational axis of the disk. The invention is also directed to a method for producing microparticles containing pharmacologically active agents, using the spinning disk apparatus. Formulations containing ophthalmically active agents are provided. Formulations exhibiting zero order release rates are also described.

Abstract: Composite biomaterials (e.g., for use as orthopedic implants), as well as methods of preparing composite biomaterials, are disclosed. The composite biomaterial includes a matrix (e.g., a continuous phase) comprising a thermoplastic, a calcium phosphate composition that is curable in vivo, or combinations thereof. The composite biomaterial also includes an isometric calcium phosphate reinforcement particles which are dispersed within the matrix.

Abstract: The present invention provides compositions and methods for facilitating fusion of bones in a joint. The present invention provides compositions and methods for promoting fusion of bones in arthrodetic procedures. In one embodiment, a method of performing an arthrodetic procedure comprises providing a composition comprising PDGF disposed in a biocompatible matrix and applying the composition to a site of desired bone fusion in a joint.

Abstract: A bone grafting material composite is provided. The bone grafting material composite includes a demineralized bone matrix (DBM) and a carboxymethyl cellulose (CMC)/glycerol gel carrier. Due to the CMC/glycerol gel carrier, the implantation ability thereof is better than that of the DBM. Therefore, the bone grafting material composite can be easily used, so that a curative effect can be greatly improved. In addition, since the CMC/glycerol gel is used as a carrier, the composite with a mobility maintained is washed out by water after surgery, so that the composite can be fixed on a damaged portion of a bone.

Abstract: The present invention relates to a triblock copolymer, that is multipurpose yet has sufficient properties particularly for medical applications, and is useful as a material having excellent flexibility and water absorbability, as well as to a method for producing the same, and a biocompatible material. The copolymer of the present invention is composed of segments A1 and A2 each composed of a polymer having a depsipeptide unit, such as a segment selected from a homopolymer of depsipeptide or a copolymer of lactide and depsipeptide, and segment B composed of polyalkylene glycol, such as PEG, and is a A1-B-A2 triblock copolymer having a number average molecular weight of 8000 to 500000. The biocompatible material of the present invention contains the triblock copolymer as a main component, and may be used as a tissue anti-adhesion barrier.

Abstract: This invention relates to stents coated with hydrophilic polymers containing S-nitrosothiols, which are able to provide local delivery of both nitric oxide and S-nitrosothiols by diffusion. This device is intended for coronary angioplasty applications with the purpose of inhibiting acute and chronic restenosis and refers to processes of stent coating with hydrophilic polymers containing incorporated S-nitrosothiols. This invention refers to an intracoronary implant device used in medical procedures, and introduces new S nitrosothiol-eluting stents coated with hydrophilic polymer multilayers. The hydrophilic polymers used for coating are polyvinyl alcohol, polyvinylpirrolidone and polyvinyl alcohol/polyvinylpirrolidone, polyvinyl alcohol/polyethylene glycol, polyvinylpirrolidone/polyethylene glycol and polyvinyl alcohol/polyvinylpirrolidone/polyethylene glycol blends.

Abstract: It has been discovered that improved yields of engineered tissue following implantation, and engineered tissue having enhanced mechanical strength and flexibility or pliability, can be obtained by implantation, preferably subcutaneously, of a fibrous polymeric matrix for a period of time sufficient to obtain ingrowth of fibrous tissue and/or blood vessels, which is the removed for subsequent implantation at the site where the implant is desired. The matrix is optionally seeded prior to the first implantation, after ingrowth of the fibrous tissue, or at the time of reimplantation. The time required for fibrous ingrowth typically ranges from days to weeks. The method is particularly useful in making valves and tubular structures, especially heart valves and blood vessels.

Abstract: The present invention provides a denatured albumin lamina, useful for repairing lesions on solid visceral organs. The lamina comprises human serum albumin, formed into a thin, pliant sheet and denatured. The denatured lamina can be sterilized and stored until used. As well, it can be impregnated with a variety of bioagents. A method for repairing a lesion on a solid visceral organ includes applying an energy-absorbing proteinaceous material to a lesion site on the solid visceral organ lesion; irradiating the proteinaceous material with energy sufficient to fuse the energy-absorbing material at least partially to the lesion site; applying a biocompatible denatured albumin lamina onto the proteinaceous material on the lesion site; and irradiating the biocompatible albumin lamina and the proteinaceous material with energy sufficient to fuse the biocompatible albumin lamina to the proteinaceous material and/or the lesion site.