Abstract: 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 (--NH.sub.2) 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.

Abstract: The present invention discloses collagen-synthetic polymer matrices which are prepared using a multiple step reaction. The first step of the reaction generally involves reacting collagen with a functionally activated synthetic hydrophilic polymer to form a collagen-synthetic polymer matrix. The synthetic hydrophilic polymer may be mono- or multifunctionally activated, but is preferably difunctionally activated, resulting in the formation of a crosslinked collagen matrix. The second step comprises modifying the collagen-synthetic polymer matrix according to one or more of the following methods: further crosslinking the matrix using a multifunctionally activated synthetic polymer, conjugating the matrix using a monofunctionally activated synthetic polymer, coupling biologically active molecules or glycosaminoglycans to the matrix, crosslinking the matrix using conventional chemical crosslinking agents, or modifying the collagen in the matrix by means of various chemical reactions.

Abstract: Collagen-based compositions useful in the attachment of tissues, or the attachment of tissues to synthetic implant materials, are disclosed. The compositions comprise collagen crosslinked using a multifunctionally activated synthetic hydrophilic polymer. A particularly preferred composition comprises fibrillar collagen, a fiber disassembly agent, and a multifunctionally activated synthetic hydrophilic polymer. Methods are disclosed for using the compositions to effect the attachment of a native tissue to the surface of another native tissue, a non-native tissue, or a synthetic implant. Also disclosed are methods of using the compositions to prevent the formation of surgical adhesions.

Abstract: Methods for completely or partially blocking, augmenting, sealing, or filling various biological lumens and voids within the body of a patient are disclosed. Lumens include arteries, veins, intestines, Fallopian tubes, and trachea. Voids include various lesions, fissures, diverticulae, cysts, fistulae, aneurysms, or other undesirable voids that may exist within a patient's body. In the most general method of the invention, an effective amount of a biomaterial is administered (e.g., via injection, catheter, or surgical implantation) into the lumen or void. Preferred biomaterial compositions for use in the present invention are disclosed.

Abstract: Collagen-based compositions useful in the attachment of tissues, or the attachment of tissues to synthetic implant materials, are disclosed. The compositions comprise collagen crosslinked using a multifunctionally activated synthetic hydrophilic polymer. A particularly preferred composition comprises fibrillar collagen, a fiber disassembly agent, and a multifunctionally activated synthetic hydrophilic polymer. Methods are disclosed for using the compositions to effect the attachment of a native tissue to the surface of another native tissue, a non-native tissue, or a synthetic implant. Also disclosed are methods of using the compositions to prevent the formation of surgical adhesions.

Abstract: The present invention discloses a novel method for preparing crosslinked biomaterial compositions for use in the augmentation of soft or hard tissue. In general, the method comprises mixing a biocompatible polymer, which is preferably collagen, with a sterile, dry crosslinking agent, which is preferably a synthetic hydrophilic polymer such as a functionally activated polyethylene glycol. Also provided are preferred processes for preparing sterile, dry crosslinking agents contained within syringes for use in the method of the invention. Methods for sterilization of the crosslinking agent include, but are not limited to, sterile filtration, aseptic processing, and e-beam or gamma irradiation. Methods for providing augmentation of soft or hard tissue using crosslinked biomaterial compositions prepared according to the method of the invention are also disclosed.

Abstract: Collagen-based compositions useful in the attachment of tissues, or the attachment of tissues to synthetic implant materials, are disclosed. The compositions comprise collagen crosslinked using a multifunctionally activated synthetic hydrophilic polymer. A particularly preferred composition comprises fibrillar collagen, a fiber disassembly agent, and a multifunctionally activated synthetic hydrophilic polymer. Methods are disclosed for using the compositions to effect the attachment of a native tissue to the surface of another native tissue, a non-native tissue, or a synthetic implant.

Abstract: Anti-adhesion films useful for the prevention of surgical adhesions are disclosed. These films comprise substrate materials (such as collagen) and hetero-bifunctional anti-adhesion binding agents, wherein the substrate material is covalently linked to receptive tissue within the body of a patient via the binding agent. Preferred binding agents comprise substrate-reactive and tissue-selective functional groups. Anti-adhesion compositions useful for the formation of such films are also disclosed.

Abstract: Various forms of chemically modified collagen are covalently crosslinked with activated synthetic hydrophilic polymers to form optically clear biocompatible conjugates useful in a variety of medical applications, particularly in ophthalmic devices. The chemically modified collagen is in substantially nonfibrillar form at pH 7 and is preferably succinylated or methylated collagen. The synthetic hydrophilic polymer is preferably an activated polymeric glycol, most preferably, a di- or multifunctionally activated polyethylene glycol. Materials and devices formed with the chemically modified collagen-synthetic polymer conjugates have good optical clarity, mechanical strength, and moldability.

Abstract: The present invention discloses a novel method for preparing crosslinked biomaterial compositions for use in the augmentation of soft or hard tissue. In general, the method comprises mixing a biocompatible polymer, which is preferably collagen, with a sterile, dry crosslinking agent, which is preferably a synthetic hydrophilic polymer such as a functionally activated polyethylene glycol. Also provided are preferred processes for preparing sterile, dry crosslinking agents contained within syringes for use in the method of the invention. Methods for sterilization of the crosslinking agent include, but are not limited to, sterile filtration, aseptic processing, and e-beam or gamma irradiation. Methods for providing augmentation of soft or hard tissue using crosslinked biomaterial compositions prepared according to the method of the invention are also disclosed.

Abstract: The present invention discloses a novel method for preparing crosslinked biomaterial compositions for use in the augmentation of soft or hard tissue. In general, the method comprises mixing a biocompatible polymer, which is preferably collagen, with a sterile, dry crosslinking agent, which is preferably a synthetic hydrophilic polymer such as a functionally activated polyethylene glycol. Also provided are preferred processes for preparing sterile, dry crosslinking agents contained within syringes for use in the method of the invention. Methods for sterilization of the crosslinking agent include, but are not limited to, sterile filtration, aseptic processing, and e-beam or gamma irradiation. Methods for providing augmentation of soft or hard tissue using crosslinked biomaterial compositions prepared according to the method of the invention am also disclosed.

Abstract: Pharmaceutically acceptable, nonimmunogenic compositions are formed by covalently binding glycosaminoglycans or derivatives thereof, to hydrophilic synthetic polymers via specific types of chemical bonds to provide biocompatible conjugates. Useful glycosaminoglycans include hyaluronic acid, the chondroitin sulfates, keratan sulfate, chitin and heparin, each of which is chemically derivatized to react with a hydrophilic synthetic polymer. The conjugate comprising a glycosaminoglycan covalently bound to a hydrophilic synthetic polymer may be further bound to collagen to form a three component conjugate having different properties. The hydrophilic synthetic polymer may be polyethylene glycol and derivatives thereof having an average molecular weight over a range of from about 100 to about 100,000. The compositions may include other components such as fluid, pharmaceutically acceptable carriers to form injectable formulations, and/or biologically active proteins such as growth factors or cytokines.

Abstract: Pharmaceutically acceptable, nonimmunogenic compositions are formed by covalently binding glycosaminoglycans or derivatives thereof, to hydrophilic synthetic polymers via specific types of chemical bonds to provide biocompatible conjugates. Useful glycosaminoglycans include hyaluronic acid, the chondroitin sulfates, keratan sulfate, chitin and heparin, each of which is chemically derivatized to react with a hydrophilic synthetic polymer. The conjugate comprising a glycosaminoglycan covalently bound to a hydrophilic synthetic polymer may be further bound to collagen to form a three component conjugate having different properties. The hydrophilic synthetic polymer may be polyethylene glycol and derivatives thereof having an average molecular weight over a range of from about 100 to about 100,000. The compositions may include other components such as fluid, pharmaceutically acceptable carders to form injectable formulations, and/or biologically active proteins such as growth factors or cytokines.

Abstract: Pharmaceutically acceptable, nonimmunogenic compositions are formed by covalently binding glycosaminoglycans or derivatives thereof, to hydrophilic synthetic polymers via specific types of chemical bonds to provide biocompatible conjugates. Useful glycosaminoglycans include hyaluronic acid, the chondroitin sulfates, keratan sulfate, chitin and heparin, each of which is chemically derivatized to react with a hydrophilic synthetic polymer. The conjugate comprising a glycosaminoglycan covalently bound to a hydrophilic synthetic polymer may be further bound to collagen to form a three component conjugate having different properties. The hydrophilic synthetic polymer may be polyethylene glycol and derivatives thereof having an average molecular weight over a range of from about 100 to about 100,000. The compositions may include other components such as fluid, pharmaceutically acceptable carriers to form injectable formulations, and/or biologically active proteins such as growth factors or cytokines.

Abstract: The present invention discloses collagen-synthetic polymer matrices which are prepared using a multiple step reaction. The first step of the reaction generally involves reacting collagen with a functionally activated synthetic hydrophilic polymer to form a collagen-synthetic polymer matrix. The synthetic hydrophilic polymer may be mono- or multifunctionally activated, but is preferably difunctionally activated, resulting in the formation of a crosslinked collagen matrix. The second step comprises modifying the collagen-synthetic polymer matrix according to one or more of the following methods: further crosslinking the matrix using a multifunctionally activated synthetic polymer, conjugating the matrix using a monofunctionally activated synthetic polymer, coupling biologically active molecules or glycosaminoglycans to the matrix, crosslinking the matrix using conventional chemical crosslinking agents, or modifying the collagen in the matrix by means of various chemical reactions.

Abstract: Pharmaceutically acceptable, nonimmunogenic compositions are formed by covalently binding glycosaminoglycans or derivatives thereof, to hydrophilic synthetic polymers via specific types of chemical bonds to provide biocompatible conjugates. Useful glycosaminoglycans include hyaluronic acid, the chondroitin sulfates, keratan sulfate, chitin and heparin, each of which is chemically derivatized to react with a hydrophilic synthetic polymer. The conjugate comprising a glycosaminoglycan covalently bound to a hydrophilic synthetic polymer may be further bound to collagen to form a three component conjugate having different properties. The hydrophilic synthetic polymer may be polyethylene glycol and derivatives thereof having an average molecular weight over a range of from about 100 to about 100,000. The compositions may include other components such as fluid, pharmaceutically acceptable carriers to form injectable formulations, and/or biologically active proteins such as growth factors or cytokines.