Devices formed of or including biocompatible polyhydroxyalkanoates are provided with controlled degradation rates, preferably less than one year under physiological conditions. Preferred devices include sutures, suture fasteners, meniscus repair devices, rivets, tacks, staples, screws (including interference screws), bone plates and bone plating systems, surgical mesh, repair patches, slings, cardiovascular patches, orthopedic pins (including bone filling augmentation material), adhesion barriers, stents, guided tissue repair/regeneration devices, articular cartilage repair devices, nerve guides, tendon repair devices, atrial septal defect repair devices, pericardial patches, bulking and filling agents, vein valves, bone marrow scaffolds, meniscus regeneration devices, ligament and tendon grafts, ocular cell implants, spinal fusion cages, skin substitutes, dural substitutes, bone graft substitutes, bone dowels, wound dressings, and hemostats. The polyhydroxyalkanoates can contain additives, be formed of mixtures of monomers or include pendant groups or modifications in their backbones, or can be chemically modified, all to alter the degradation rates. The polyhydroxyalkanoate compositions also provide favorable mechanical properties, biocompatibility, and degradation times within desirable time frames under physiological conditions.

Medical devices and applications of polyhydroxyalkanoate polymers

Single and double density biopolymer foams, composite biopolymer foams including both single and double density foams, and methods of preparing these foams and composite foams are described. Also described are biocompatible constructs which include single or double density biopolymer foams and extracellular matrix particulates and methods of preparing these constructs. The foams, composite foams, and biocompatible constructs of the invention can be used in tissue repair and reconstruction.

Biopolymer foams for use in tissue repair and reconstruction

An implant for deployment in select locations or select tissue for regeneration of tissue is disclosed. The implant comprising collagen and or other bio-resorbable materials, where the implant may also be used for therapy delivery. Additionally, the implant may be “matched” to provide the implant with similar physical and/or chemical properties as the host tissue.

Devices and methods for treating defects in the tissue of a living being

Crosslinked polymer compositions comprise a first synthetic polymer containing multiple nucleophilic groups covalently bound to a second synthetic polymer containing multiple electrophilic groups. The first synthetic polymer is preferably a synthetic polypeptide or a polyethylene glycol that has been modified to contain multiple nucleophilic groups, such as primary amino (-NH2) or thiol (-SH) groups. The second synthetic polymer may be a hydrophilic or hydrophobic synthetic polymer which contains, or has been derivatized to contain, two or more electrophilic groups, such as succinimidyl groups. The compositions may further comprise other components, such as naturally occurring polysaccharides or proteins (such as glycosaminoglycans or collagen) and/or biologically active agents. Also disclosed are methods for using the crosslinked polymer compositions to effect adhesion between a first surface and a second surface; to effect tissue augmentation; to prevent the formation of surgical adhesions; and to coat a surface of a synthetic implant.

Crosslinked polymer compositions and methods for their use

Improved Implant assemblies and methodologies provide immuno-protection for implanted allografts, xenografts, and isografts. The assemblies and methodologies establish an improved chamber for holding the implanted cells. The chambers include first and second wall elements and an intermediate sealing element. The first and second wall elements overlie an open area in the sealing member to form a chamber for holding cells for implantation. A sealed region is created between the wall elements and the sealing element body to close the chamber. In one arrangement, the sealed region is created by means of a sonic weld made while the implanted cells are present in the chamber. In another arrangement, the sealed region is created by means of applying an external force to compress the peripheral edges of the wall elements and the sealing element together while the implanted cells are present in the chamber.

Closed porous chambers for implanting tissue in a host

Collagen implants that are useful as wound healing matrices are characterized by being formed of collagen fibrils that are not chemically cross-linked, and having a bulk density of 0.01 to 0.3 g/cm3 and a pore population in which at least about 80 % of the pores have an average pore size of 35 to 250 microns. The implants are capable of promoting connective tissue deposition, angiogenesis, reepithelialization, and fibroplasia. The wound healing matrix also serves as an effective sustained delivery system for bioactive agents.

Collagen wound healing matrices and process for their production

Injectable implant compositions comprise a biocompatible ceramic matrix present in a fluid carrier, where the ceramic matrix comprises particles having a size distribution in the range from 50 μm to 250 μm. Optionally, the compositions may further comprise collagen, where the relative amounts of collagen and ceramic matrix at least partly determine the physical properties of implants formed by injecting the compositions. The fluid carrier is an aqueous buffered medium, typically including an organic polymer base material when there is no collagen present in the composition. The compositions are particularly suitable for repair and augmentation of soft and hard tissues by injection.

Injectable ceramic compositions and methods for their preparation and use

Collagen implants that are useful as wound healing matrices are characterized by being formed of collagen fibrils that are not chemically cross-linked, and having a bulk density of 0.01 to 0.3 g/cm 3 and a pore population in which at least about 80% of the pores have an average pore size of 35 to 250 microns. The implants are capable of promoting connective tissue deposition, angiogenesis, reepithelialization, and fibroplasia. The wound healing matrix also serves as an effective sustained delivery system for bioactive agents.

Processes for producing collagen matrixes and methods of using same

In accordance with the present invention, stabilized dispersions of collagen fibers that have been treated in order to inactivate infectious agents and methods of stabilizing such collagen fibers are provided.

Method of controlling structure stability of collagen fibers produced from solutions or dispersions treated with sodium hydroxide for infectious agent deactivation

The transforming growth factor-8 (TGF-P) family of proteins' includes two homologs, TGF-Pl and TGF-82, that share approximately 70% sequence identity. TGF-pl and TGF-fi2 have similar biological activities in most, but not all systems TGF-8 exhibits a pattern of biological responses that suggest that one of the principal functions of this factor may be to promote the accumulation of connective tissue during tissue repair.' TGF-p is released at sites of tissue damage during degranulation of platelet alpha granules5 and is also synthesized by a variety of cells that are present during inflammation and repairP-I0 A transient rise in TGF-P has been detected in wire mesh chambers implanted subcutaneously in rats as a model of wound repair?' In vitro, TGF-p is chemotactic for mon0cytes~~J3 and fibroblast^.'^ In cultured cells, it promotes the accumulation of connective tissue matrix by stimulating secretion of matrix molecules, as well as by inhibiting protease production and stimulating secretion of protease inhibitors (see Roberts et aZ.1 for review). It can also stimulate fibroblasts to contract collagen gels.'5 TGF-p is also a potent inhibitor of proliferation for many cells in culture,' including e n d o t h e l i ~ m ~ ~ , ' ~ and keratinocytes?8-z0 It might, therefore, be expected to have an adverse effect on endothelial proliferation in granulation tissue formation, and on the reepithelialization of dermal wounds. It has been shown that TGF-P stimulates the for-

Hugh Mcmullin

Papers

Collagen wound healing matrices and process for their production

Injectable ceramic compositions and methods for their preparation and use

Processes for producing collagen matrixes and methods of using same

Method of controlling structure stability of collagen fibers produced from solutions or dispersions treated with sodium hydroxide for infectious agent deactivation

Transforming Growth Factors‐β1 and β2 Enhance Connective Tissue Formation in Animal Models of Dermal Wound Healing by Secondary Intent