Abstract: The present invention relates to an elastin-based biomaterial and to a method of using same to effect tissue repair or replacement. The invention further relates to a method of securing the biomaterial to existing tissue.

Abstract: Tissue is procured from a human or animal donor. The tissue may be fixed by application of a fixative. Cellular components which would cause rejection are removed from tissue by a chemical treatment that allows the extracellular matrices (ECM) to retain their original shapes, biological structures and ultrastructures, locations and durability. The resulting ECM serves as a cell scaffold on which living cells are seeded to form a lifegraft for implanting or for allograft reconstruction.

Abstract: Microfibrillar collagen and a superabsorbent polymer are combined in a hemostatic bandage which both absorbs blood and induces clotting.

Abstract: Cell culture substrates comprising dried films of native fibrillar collagen produced by a method in which collagen fibers are hydrolyzed in acid, solubilized, and reformed as gels on porous surfaces under non-physiologic salt conditions to produce large fibers with the striations characteristic of collagen fibers found in vivo. The gels are collapsed onto the porous surfaces by drawing the interfibril fluid out of the gel through the underside of the porous surface and then dried to form films. Dried collagen films made in this manner retain native fibrillar collagen structure and excellent diffusion characteristics. Native fibrillar collagen films produced according to the methods of the invention are useful as cell culture substrates. They have particularly advantageous properties for growth and differentiation of epithelial cells. This effect is synergistically enhanced by addition of butyric acid as a differentiation inducing agent.

Abstract: A biopsy needle has coaxial, telescopically interengaged stylet, inner and outer cannulas which are axially and rotatably displaceable relative to one another. The stylet has a distal portion provided with a cutting recess for severing a biopsy specimen from a site in a patient, and the inner cannula has a distal portion for cutting and capturing the specimen in the recess for removal from the site upon withdrawal of the needle from the patient. The distal portion of the inner cannula is partially cut away to provide an insert recess which supports a semi-circular insert of hemostatic collagen which remains at the site upon removal of the needle to minimize hemorrhagic complications by promoting blood clotting. The insert and the distal portion of the inner cannula have radially outer surfaces of corresponding radius whereby the distal portion of the inner cannula and the insert supported thereon are received within the distal end of the outer cannula prior to use of the needle.

Abstract: The present invention provides improved osteogenic compositions having enhanced by the sorption of growth factors, of nutrient factors, or drugs onto or into the compositions. Compositions may consist of collagen and demineralized bone materials onto and into which growth factors, antimicrobial agent, a nutrient factors, or other soluble factors may be sorbed to enhance the osteogenic factor. These materials can be used in a wide range of clinical procedures to replace and restore osseous or periodontal defects.

Abstract: Soft tissue implants can be constructed by forming an outer membrane into a closed pouch and filling material in that pouch. A composition for use as a filler material in such a soft tissue implant may include elastin and collagen. The filling material has collagen as a component thereof, and this collagen can be cross-linked or not cross-linked. Methods of making such implants are described.

Abstract: A method of promoting collagen reformation in vivo comprises applying a mixture of calcium hydroxide and oleum pedum tauri, optionally with pharmaceutically tolerable auxiliaries, to the tissue in need of collagen reformation. Enhanced bone healing results, following general surgery, dental surgery, tooth implantation etc.

Abstract: A soft tissue closure system for closing percutaneous puncture sites or soft tissue voids, its method of manufacture and method of use are disclosed. The system comprises a delivery means and a self-expandable, resorbable implant disposed within the delivery means in a compressed configuration. Upon release of the implant member from the system within a soft tissue void, the implant member self-expands to conform to the shape of the soft tissue void and seals the void.

Abstract: Suturable, biocompatible, control-resorbing membranes are disclosed for use in guided tissue regeneration, comprising a cross-linked collagen material either obtained by crosslinking a starting collagen material in the coagulated state produced by coagulation of a collagen material gel with a coagulating agent or obtained by crosslinking of a sponge of a collagen material on which a collagen material gel has been poured before performing the crosslinking.

Abstract: A method of treating aldehyde-tanned biological tissue minimizes in vivo calcification and reduces cytotoxicity without impairing the mechanical strength of the tanned tissue. The method includes the step of treating the aldehyde-tanned biological tissue with at least one liquid polyol having the formula: ##STR1## where R is CH.sub.2 OH or an alkyl group, and R' is H, an alkyl group or an O-acyl where the acyl is C.sub.2 -C.sub.9 or a carboxyalkyl; or ##STR2## where R is H or an alkyl group, and R' is H, an alkyl group, O-alkyl or O-carboxyalkyl. Preferred polyols are propylene glycol, 1,3-propanediol, 2,3-butylene glycol and glycerol, and the polyol is preferably a diol.

Abstract: A bioresorbable and hemostatic plug for embolization made from a collagen piece is compressed so as to be longitudinally insertable into a tubular biological vessel such as a blood vessel to be occluded. The collagen piece is capable of expanding radially inside the vessel by absorbing fluid such as the blood and thereby providing mechanical fixation in and occlusion of the vessel. Two such collagen pieces may be used with a spacer of a different material in between. Different kinds of therapeutic agents can be bonded to or physically absorbed by the collagen pieces so as to be delivered to the site of occlusion.

Abstract: The invention relates to three-layer vascular prostheses comprising an internal layer 1, a middle layer 2 and an external layer 3 which is characterized in that the middle layer 2 is made from a physiologically non-resorbable, porous material, and the internal layer 1 and the external layer 3 are self-supporting and are made from a physiologically resorbable, fibrillar material, and are tanned. The internal layer 1 and the external layer 3 preferably consist of collagen, but have different resorbability. The middle layer 2 is preferably made from inert fibers, preferably synthetic fibers, by means of textile technology. The biologically resorbable layers preferably comprise chemically or physically bonded or incorporated pharmacologically active substances.

Abstract: Collagen-containing sponges comprising an absorbable gelatin sponge, collagen, and an active ingredient are disclosed as are methods of enhancing wound healing of external and internal wounds using such sponges.

Abstract: A surgical method for implanting cadaver collagen for the restoration of lesions caused by the loss of collagen. The skin is perforated and a pocket is created under the skin. Human cadaver collagen is then introduced into the pocket and the skin perforation is closed. Over the next several months, the cadaver collagen is replaced by endogenous collagen.

Abstract: Preparing chemically cross-linked collagenous biological graft material by preparation processes which include the step of altering the locations and/or orientations of chemical cross-linkages formed during the collagen cross-linking process. Embodiments of the method include various processes whereby physical force, stress or movement is applied to alter the relative positioning of the collagen fibers within the graft materials during at least the initial period of exposure to the collagen cross-linking reagent.

Abstract: Bioprosthetic materials, either natural or synthetic, are treated with trivalent aluminum or iron cations, or salts, to prevent in vivo calcification. Such bioprosthetic materials include porcine aortic valve leaflets, bovine pericardium, aortic homografts, biocompatible elastomers, and the like which are intended for invasive, or in-dwelling use in a human or animal body. Simple incubation of the natural bioprosthetic materials in an ion-containing solution, such as aqueous AlCl.sub.3 or FeCl.sub.3, prior to implantation has been found to inhibit calcification of the biomaterial over a prolonged period, and to do so without adverse side effects. Incorporation of an aluminum-containing compound into the formulation for polymers, such as polyurethane, has also been found to inhibit calcification with no adverse side effects.

Abstract: Cell-penetrable medical material made of denatured collagen which is prepared by heating, in the presence of water is disclosed, the collagen having cross-linking structure. Artificial skin prepared by using this medical material as a wound-contacting layer (2) is also disclosed.

Abstract: A soft tissue closure system for closing a percutaneous puncture site or soft tissue voids, its method of manufacture and method of use are disclosed. The system comprises a delivery means and a self-expandable, resorbable implant disposed within the delivery means in a compressed configuration. Upon release of the implant member from the system within a soft tissue void, the implant member self-expands to conform to the shape of the soft tissue void and seals the void.

Abstract: A method for molecularly crosslinking amino acid containing polymers by photoactivating chemical crosslinkers which have been combined with the polymers. Collagen crosslinked by this method can be used as a bioadhesive for sutureless closures of the skin and eye or as a superhydrated material for contact lenses, moist bandage contact lens, lens or corneal implant material, or as a drug delivery mechanism.

Abstract: A puncture seal device for stemming the flow of blood from a punctured blood vessel has an elongated outer sheath affixed to a generally tubular housing where the housing contains a manually actuable slide which is affixed to a rigid tubular pusher member coaxially disposed within the outer sheath. Also contained within the outer sheath in longitudinal alignment with the pusher and distally thereof is a ring-shaped plug of a hemostatic material. The assembly thus far described may be fitted over a tubular introducer or the body of a catheter and then advanced therealong until the distal end of the outer sheath is proximate a bleeding blood vessel. By actuating the pusher member, the hemostatic plug surrounding the introducer or catheter is ejected from the distal end of the outer sheath and held in abutting relationship to the bleeding blood vessel.

Abstract: A composite living skin equivalent is described comprising an epidermal layer of cultured keratinocyte cells, a layer of non-porous collagen, and a dermal layer of cultured fibroblast cells in a porous cross-linked collagen sponge matrix. Preferably the non-porous collagen is Type 1, Type 3 or mixtures of Types 1 and 3 bovine collagen, which has been pepsin treated. A process for preparing the skin equivalent is described, as well as a test kit for in vitro testing of the skin equivalent. The skin equivalent has use for skin grafting as well as in vitro testing of the effects of various substances on skin.

Abstract: A method for the treatment of bone lesions or bone deficiencies in a living mammal comprising administering a composition comprising an inorganic phase and an organic phase wherein the inorganic phase comprises a porous particulate TCP ceramic or a nonporous or microporous particulate HAP ceramic or a mixture of porous particulate TCP ceramic and nonporous or microporous particulate HAP ceramic, wherein the organic phase comprises a purified hydrated collagen product which is mixed with and forms a continuous or substantially continuous surface coating over said inorganic phase(s) and a hydrated collagen-demineralized bone product which is mixed with and forms a substantially continuous surface coating over said purified hydrated collagen product surface coating or the organic phase comprises a hydrated collagen-demineralized bone product which is mixed with and forms a continuous or substantially continuous surface coating over said inorganic phase and a purified hydrated collagen product which is mixed with

Abstract: Disclosed is a cell-penetrable medical material in which cells can invade, comprising denatured collagen with helix content of 0 to 80%, and carrier substance having higher resistance to enzyme decomposition than the denatured collagen. An artificial skin in which this medical material is used as the wound contact layer, and its preferred manufacturing methods are also disclosed.

Abstract: A composition for use in bone repair, in particular, in only procedures, which comprises calcium phosphate mineral particles in admixture with atelopeptide reconstituted fibrillar collagen preparations is disclosed. This composition is non-immunogenic and encourages the fusion of host bone with new bone growth through the implant. Additional processes for curing the implant to improve its compressive strength include heat curing, maturation, and cross-linking.

Abstract: An osteogenic composition is obtained from demineralized bone tissue.

Abstract: Mineralized collagen is prepared by forming calcium phosphate mineral under mild agitation in situ in the presence of dispersed collagen fibrils. A stable composition is obtained with desirable physical characteristics mimicking the characteristics of bone.

Abstract: The present invention provides a biologically compatible collagenous reaction product comprising ethylenically unsaturated or polymeric substituted collagen, the monomeric substituents being essentially free of nitrogen, e.g., methacrylate, styrene, polyvinyl, ethylene. The collagenous reaction product can be polymerized, e.g., by exposure to UV irradiation, chemical agents or atmospheric oxygen, and molded to form useful medical implant articles. Methods of preparation are also provided.

Abstract: A matrix for implantation in a mammalian host comprising biocompatible, mineral-free, insoluble Type-I bone collagen which may be allogenic or xenogenic to the host, and which, when implanted in the host, is biodegradable. The collagen is treated with a collagen fibril modifying substance such as acidified acetonitrile, chloroform, or dichloromethane, or by heating in an aqueous environment to a temperature of 37.degree.-65.degree. C. The treated material undergoes a change in morphology involving a significant increase in its surface area as measured by various methods. Under the scanning electron microscope the material has an "oyster shell" appearance with many pits and micropores.

Abstract: Disclosed is a matrix material for implantation in a mammalian host comprising biocompatible mineral-free type I bone collagen, xenogenic to the host, and biodegradable therewithin. The matrix is manufactured from protein-extracted bone powder treated with certain swelling agents to increase its surface area and porosity. The matrix may be combined with osteogenic protein to induce reliably and reproducibly endochondral bone formation. It also can be used as a surface coat around implantable prosthetic devices to promote cellular ingrowth or as a carrier for sustained release of various therapeutic compositions.

Abstract: A method of bonding collagen to synthetic polyester fibers, particularly DACRON. The method involves providing synthetic polyester fabric fibers having repeating carbonyl groups, hydrogenating the repeating carbonyl groups and then conducting a transesterification step which includes the addition of free amine groups. The free amine groups are reacted with a bifunctional crosslinking agent to produce modified polyester fibers. The final step involves adding collagen to the modified polyester fibers for a time sufficient to produce covalent bonding of the collagen to the fibers.The invention also involves the making of a fabric matrix comprised of synthetic polyester fibers, particularly DACRON, and collagen being covalently bound to the fibers. Such matrix can be utilized in ligament prosthesis design.

Abstract: Ophthalmologic collagen coverings derived from animal eyes and a process for preparing such coverings comprising treatment of a fibrous tunic of an animal eye with an alkali metal hydroxide in a saturated solution of a salt of an alkali metal, followed by neutralization, dissolution in an aqueous solution of an organic acid, purification of the resulting solution of collagen by dialysis against a buffer solution while bringing the solution of collagen to a pH of 4.5 to 7.5 and drying the thus-obtained solution of collagen simultaneously with shaping spherical coverings therefrom.

Abstract: The present invention is a method for treating bony defects. The method involves contacting the bony defect with a formable composition and allowing the formable composition to solidify. The formable composition is comprised of 2-40% of reconstituted fibrillar atelopeptide collagen and 60-98% calcium phosphate mineral by weight exclusive of moisture. After the formable composition is placed in intimate contact with the bony defect, it is allowed to solidify until it acquires an additional characteristic selected from the group consisting of a compressive modulus of at 10 N/cm.sup.2 or a tensile strength of at least 1 N/cm.sup.2. The method can be used to repair a variety of bony defects such as bone non-union, fresh fractures, periodontal bony pockets, tooth extraction sockets and jaw cysts. Further, the composition can be used to augment an alveolar ridge.

Abstract: Human-skin collagen fibers are obtained from sterile pieces of human skin by first comminuting the sterile skin and then mixing the comminuted sterile skin with a sterile aqueous solution of an alkaline-metal or alkaline-earth salt to form a suspension. This suspension is then diluted with a promoter of fibrillogenesis taken from the group formed by acetylated glucosamine, n-acetyl neuraminic acid, and mixtures thereof and the pH of the suspension is set to a value between 4 and 6. The diluted suspension is then left to ripen while fibers grow in it. Collagen fibers are then separated from the suspension and are checked under a microscope for the presence of protein impurities. If any such fraction is then found the fibers are rinsed by agitation with an atoxic aqueous solution of a nonionic detergent, then the residual protein impurities are separated out to obtain an aqueous suspension of collagen fibers having no foreign matter, and finally the collagen fibers are rinsed in steriized water.

Abstract: The present invention embodies a composition particularly adapted for use as an ophthalmic viscosurgical material for use in the anterior chamber, posterior chamber and vitreous cavity of the eye consisting essentially of a mixture of purified collagen Type II and Type IV, which is the basic composition of naturally occuring vitreous in the eye. The invention further embodies an improved ophthalmic viscosurgical procedure wherein the anterior chamber of the eye is filled with a space - filling corneal endothelium and ocular tissue protective surgical material, the improvement comprising the utilization of an ophthalmic surgical material having the above described composition.

Abstract: An uncured or partially cured, collagen-based material is delivered to a selected site in a blood vessel and is crosslinked in the blood vessel by laser energy or other suitable energy to form an endovascular stent. The collagen-based material can be delivered to the blood vessel as a coating on an inflatable balloon mounted on the distal end of a catheter. The collagen-based material can also be delivered to the blood vessel in liquid form and forced through a porous balloon to form a tubular configuration. The collagen-based material is preferably crosslinked by laser radiation carried through an optical fiber to a diffusing tip located within the balloon. In another embodiment, an endovascular stent is formed by rolling a flexible sheet of biologically-compatible material onto an outside surface of an inflatable balloon.

Abstract: Ophthalmologic collagen coverings derived from animal eyes and a process preparing such coverings comprising treatment of a fibrous tunic of an animal eye with an alkali metal hydroxide in a saturated solution of a salt of an alkali metal, followed by neutralization, dissolution in an aqueous solution of an organic acid, purification of the resulting solution of collagen by dialysis against a buffer solution while bringing the solution of collagen to a pH of 4.5 to 7.5 and drying the thus-obtained solution of collagen simultaneously with shaping spherical coverings therefrom.

Abstract: Ophthalmologic collagen coverings derived from animal eyes and a process preparing such coverings comprising treatment of a fibrous tunic of an animal eye with an alkali metal hydroxide in a saturated solution of a salt of an alkali metal, followed by neutralization, dissolution in an aqueous solution of an organic acid, purification of the resulting solution of collagen by dialysis against a buffer solution while bringing the solution of collagen to a pH of 4.5 to 7.5 and drying the thus-obtained solution of collagen simultaneously with shaping spherical coverings therefrom.

Abstract: A method of repairing connective tissue uses a heterograft for supporting ingrowth of ligament or tendon connective tissue to replace damaged connective tissue in a subject which is composed of a plurality of long, thin fibers extracted from animal connective tissue having generally the same mechanical properties as the tissue to be replaced. The individual fibers are extracted by a sequence of chemical treatments and mechanical treatments, purified to eliminate foreign material from the fibers, and cross-linked to a degree that causes their shrinkage temperature to have a preselected value that corresponds to the desired tensile strength, allows only a preselected amount of water retention by the fibers in order to enhance attraction of fibrogenic cells to the fiber surfaces, and avoids producing foreign body reaction to the heterograft. The fibers are maintained generally parallel in a bundle or weave.

Abstract: Implants containing a reasonably biocompatible fabric, which is to be exposed to blood flow after implantation, are rendered biocompatible and substantially impervious to blood, by applying a collagen composition containing soluble collagen, and preferably also collagen fibers, to the fabric in such a manner that the collagen composition penetrates into the interstitial spaces of the fabric. The fabric retaining collagen composition is then incubated at elevated temperature for sufficient time to form collagen fibers from the soluble collagen. Thereafter, the implant is dried. The steps of applying collagen composition, incubating and drying are repeated approximately two to four times. The implants, particularly when they comprise tubular vascular grafts, are tested for porosity by placing a pressurized column of aqueous solution, such as saline, into their interior.

Abstract: A biocompatible collagen/mineral composition which comprises a mixture of 2-40% reconstituted fibrillar atelopeptide collagen and 60-98% calcium phosphate mineral by weight, exclusive of water, is disclosed. The composition has a sterility assurance factor of at least as low as 10.sup.-6 and either a compressive modulus of at least 10 N/cm.sup.-2 or a tensile strength of about 3-12 N/cm.sup.-2.

Abstract: Octacalcium phosphate and hydroxyapatite are provided, where octacalcium phosphate is produced as novel single crystals and organized polycrystalline structures that are non-dense. The crystals serve as fibers, which find application in a wide variety of applications as well as coatings of prosthetic devices or other materials which may have physiological application.

Abstract: An antithrombogenic material is described, comprising an expanded polytetrafluoroethylene base having a collagen layer provided on the surface thereof, and further provided thereon a composite layer of collagen and a mucopolysaccharide, and said collagen is crosslinked with a crosslinking agent.

Abstract: A collagen-hydrogel for promoting epithelial cell growth is shown. Also shown is an optical lens for the eye, fabricated from the collagen-hydrogel, which, when affixed to Bowman's membrane, promotes and supports epithelial cells growth and enables corneal epithelium of the cornea of an eye, during the healing process, to attach to and cover the anterior surface of the lens implanting the same. The collagen-hydrogel is a hydrogel polymer formed by the free radical polymerization of a hydrophilic monomer solution gelled and crosslinked in the presence of an aqueous solution of macromolecules to form a three dimensional polymeric meshwork for anchoring macromolecules. Macromolecules comprising a constituent of a ground substance of tissue, which in the preferred embodiment is a native collagen, are interspersed within the polymeric network forming the hydrogel resulting in a collagen-hydrogel for promoting epithelial cell growth.

Abstract: A process for producing a collagen-based cross-linked biopolymer is provided in which a collagen solution free of low-molecular impurities is saturated with nitrogen protoxide, its concentration is brought to maximum 80 mass percent and the solution is exposed to an ionizing radiation in a dose of 0.5 to 15 kGy. An implant for hermetization of corneal and scleral wounds involved in eye injuries prepared from said bipolymer has the shape and size that provide for complete hermetization of said wounds. The method for its preparation comprises saturation of a collagen solution free of impurities and having a concentration of 0.2 to 1.3 mass percent, with nitrous oxide, filling of a mould with said solution and its exposure to an ionizing radiation in a dose of 0.5 to 15 kGy. The resultant blank is dried to a moisture content in its biopolymer of 30 to 50 mass percent, whereupon the blank is given the shape and size of a required implant.

Abstract: Disclosed is a matrix material for implantation in a mammalian host comprising biocompatible mineral-free type I bone collagen, xenogenic to the host, and biodegradable therewithin. The matrix is manufactured from protein-extracted bone powder treated with certain swelling agents to increase its surface area and porosity. The matrix may be combined with osteogenic protein to induce reliably and reproducibly endochondral bone formation. It also can be used as a surface coat around implantable prosthetic devices to promote cellular ingrowth or as a carrier for sustained release of various therapeutic compositions.

Abstract: This invention relates to a biodegradable collagen matrix having a pore size and morphology which enhances the healing of a wound. It further relates to a process for preparing the matrix. One embodiment of the invention comprises a biodegradable matrix which comprises collagen, hyaluronic acid and fibronectin. Other embodiments include a process which comprises freeze drying a dispersion containing collagen, crosslinking the collagen via two crosslinking steps and freeze drying the crosslinked matrix.

Abstract: Production of a chemically modified, crosslinkable, telopeptide-containing, naturally crosslinked, solubilized collagen from tissue obtained from a sole human donor, for implanting in the same donor, by chemically modifying the tissue, e.g. by acylation and/or esterification, to form an autoimplantable, crosslinkable, telopeptide-containing naturally crosslinked, collagen, product, as a completely solubilized collagen solution, optionally of high index of refraction for correcting sight, or as a partially solubilized collagen suspension; and use of the product for altering the condition of in situ tissue of the same human donor by autoimplantation, such as by crosslinking the product to form an implant device, by placing an effective amount of the product at the tissue site and crosslinking the product in situ, or by partially crosslinking the product and placing an effective amount thereof at the tissue site and optionally further crosslinking the product in situ.

Abstract: A method and surgical implant article for enhancing the regeneration of periodontal connective tissue at tooth root surfaces exposed by periodontal surgery wherein the exposed root surfaces are covered with a surgical implant article which is a membrane which excludes contact between the root surfaces and gingival epithelium and gingival connective tissue but permits migration to the root surfaces of PDL cells, the membrane being constructed of a non-toxic, nonimmunogenic, bio-absorbable material.

Abstract: A composite living skin equivalent is described comprising an epidermal layer of cultured keratinocyte cells, a layer of non-porous collagen, and a dermal layer of cultured fibroblast cells in a porous cross-linked collagen sponge matrix. Preferably the non-porous collagen is Type 1, Type 3 or mixtures of Types 1 and 3 bovine collagen, which has been pepsin treated. A process for preparing the skin equivalent is described, as well as a test kit for in vitro testing of the skin equivalent. The skin equivalent has use for skin grafting as well as in vitro testing of the effects of various substances on skin.The questions raised in reexamination request No. 90/003,418, filed Apr. 25, 1994, have been considered and the results thereof are reflected in this reissue patent which constitutes the reexamination certificate required by 35 U.S.C. 307 as provided in 37 CFR 1.570(e).