Abstract: This process, which essentially comprises the following steps:esterification of the free acid groups of the collagen,transformation of the esterified groups into hydrazides groups,transformation of the hydrazide groups into azide groups by the action of nitrous acid, is characterized in that each step is separated by a rinsing in an aqueous salt solution, and in that the step of transformation of esterified groups into azide groups and the step of transformation of hydrazide groups into azide groups by the action of nitrous acid, are performed in the presence of salt.

Abstract: A method for producing a biodegradable polymer having a preferentially oriented pore structure and a method for using the polymer to regenerate damaged nerve tissue is disclosed. The preferentially oriented pores are produced by an axial freezing process and serve to promote proper vascularation and regeneration of the damaged nerve. Preferably, the biodegradable polymer comprises uncrosslinked collagen-glycosaminoglycan.

Abstract: A mechanically stable, conformable collagen wound dressing sheet material is fabricated by lyophilizing (freeze-drying) a collagen composition and compressing the porous pad thus produced at a pressure between about 15,000-30,000 p.s.i. The sheet material thus produced may also be treated with optional dehydrothermal crosslinking known in the art. In addition to mechanical stability and conformability, the sheet material demonstrates high absorptivity, i.e., about 15-20 times its weight in isotonic saline, making it highly useful as a medical or surgical dressing or as a carrier for other medicaments such as antibiotics. The sheet material may be impregnated with thrombin.

Abstract: An implantable collagen-based material is prepared by (i) pretreating a collagen-based material with a member selected from the group consisting of fluorescein isothiocyanate, picrylsulphonic acid and nitrous acid, in an amount sufficient to render some of the amino acid side chains of the material unable to bind with a cross-linking agent, and (ii) reacting the pretreated collagen-based material with a cross-linking agent whereby at least some of the remaining amino acid side chains are linked together.

Abstract: The invention relates to a process to prepare vessel prostheses formed from a porous basic body and an impregnating coating of crosslinked gelatin for sealing the pores.Crosslinking takes place accompanied by the use of a diisocyanate. The impregnating coating has good mechanical and physiological properties.

Abstract: Chemically-modified collagen is prepared by reacting native collagen with a di or tri-carboxylic acid halide, di or tri-sulfonyl halide, di or tri-anhydride, or di or tri-reactive active ester coupling agent. The reaction is done in a controlled manner so that the degree of cross-linking is limited. Any remaining lysine epsilon amino groups present in the coupled collagen product may be converted to ureido, .beta.-malicamino carboxyamido or sulfonamido groups by isocyanate, epoxy succinic acid, acid halide, anhydride, sulfonyl halide or active ester aminemodifying agents. The resultant soluble product when dissolved in a physiological buffer provides a viscoelastic solution having therapeutic application in a variety of surgical procedures, particularly in ophthalmic surgery. This viscoelastic solution "melts," i.e., exhibits a dramatic loss of viscosity, when subjected to temperatures of between 32.degree. and 48.degree. C.

Abstract: A prosthetic meniscus is disclosed which can be implanted in a humanoid knee, and which can act as a scaffold for regrowth of native meniscal tissues. The meniscus comprises a three dimensional array of collagen fibers interspersed with glycosaminoglycan molecules. The collagen fibers are present at a concentration of about 65 to 98 percent by dry weight, and the glycosaminoglycan molecules are present at a concentration of about 1 to 25 percent by dry weight. Crosslinks are provided by at least a portion of the glycosaminoglycan molecules, and may consist of at least one of the group comprising chondroitan 4-sulfate, chondroitan 6-sulfate, keritan sulfate, dermatan sulfate, heparin sulfate, and hyaluronic acid.

Abstract: Chemically-modified collagen is prepared by reacting native collagen with a di or tri-carboxylic acid halide, di or tri-sulfonyl halide, di or tri-anhydride, or di or tri-reative active ester coupling agent. The reaction is done in a controlled manner so that the degree of cross-linking is limited. Any remaining lysine epsilon amino groups present in the coupled collagen product may be converted to carboxyamido or sulfonamido groups by acid halide, anhydride, sulfonyl halide or active ester amine-modifying agents. The resultant product when dissolved in a physiological buffer provides a viscoelastic solution having therapeutic application in a variety of surgical procedures, particularly in ophthalmic surgery. This viscoelastic solution "melts," i.e., exhibits a dramatic loss of viscosity, when subjected to temperatures of between 32.degree. and 48.degree. C.

Abstract: A wound dressing comprising a crosslinked collagen matrix; a bioabsorbable adhesive coated on one surface of the collagen matrix; a multilayer polymer film imparting pre-selected moisture vapor and gas transmissivity to the dressing, secured to the opposite surface of the collagen matrix; and an adhesive securing the collagen matrix to the polymer film.

Abstract: A collagen impregnated synthetic vascular graft including a synthetic vascular graft substrate and cross-linked collagen fibril is formed by depositing an aqueous slurry of collagen fibrils in the lumen of the graft and massaging to insure intimate mixing of the fibrils into the porous structure of the substrate. After massaging, the collagen is dried and cross-linked. Repeated applications and massaging and drying further reduce porosity of the graft.

Abstract: A process for treating biological tissue prior to implantation to mitigate the calcification of the tissue following implantation comprises incorporating acetylsalicylic acid into the tissue in an amount effective to reduce calcification of the tissue after it is implanted. In accordance with one embodiment, the process involves convalently binding the acetylsalicylic acid to the tissue via a coupling agent.

Abstract: Collagen-based compositions for augmenting soft tissue, wound dressings, implants, injectable formulations or other drug delivery systems, comprising resorbable collagen matrix beads, the beads having an average pore size of from 50 to 350 microns, and the collagen comprising from 1 to 30% by volume of the beads, the collagen matrix being sufficiently open to stimulate cellular ingrowth therethrough and yet sufficiently stiff and non-compressible to fill and protect a wound, and the formulation being sufficiently moisture and gas permeable to prevent liquid pooling on a wound and to permit sufficient oxygen diffusion for promoting wound healing.

Abstract: Anisotropic mammalian diaphragm is crosslinked using, for example, glutaraldehyde and used as a surgical implant graft for repair of tissues which accommodate to relative movement of tendons, joints, etc.

Abstract: A process for preparing collagen tubes includes extruding an aqueous gel containing about 1.5% native collagen through a cylindrical spinneret equipped with a central concentric tube designed to receive a part of a coagulation bath, followed by coagulation of the internal and external walls of the tube, leaving the spinneret in a coagulation bath constituted by about 70% acetone and 30% ammonia, followed by drying. Following drying, the collagen tube may be subjected to reticulation by dehydration carried out at about 80.degree. C. under a pressure of about 0.1 mm of Hg (vacuum) for about 24 hours. The reticulated collagen tube may eventually be subjected to a treatment which permits the introduction of azide groups onto the molecule without requiring that the collagen be coupled to any external molecule.

Abstract: A xenogeneic tissue replacement for nonfunctional flexor tendon pulley comprising crosslinked, bovine or porcine or other anisotropic mammalian diaphragm and method of use are disclosed.

Abstract: A sterile body implant is derived from a body structure having as its major protein component collagens in the form of extracellular matrix. The body structure is treated to remove cellular membranes, nucleic acids, lipids and cytoplasmic components. Such structures are implanted internally in the body or externally on the body in a variety of medical uses.

Abstract: Xenogeneic tissue implants prepared by precrosslinking proteins in xenogeneic tissue using, for example, glutaraldehyde, and thereafter irradiating the crosslinked tissue with high energy radiation, e.g. gamma radiation, to sterilize, reduce the immunogenicity and improve the compliance and physical properties of the tissue are disclosed.

Abstract: The present invention relates to a composition consisting of an association of collagen with an antiseptic and/or antiinflammatory active principle, the process for its preparation and its use for the production of a pharmaceutical composition.The pharmaceutical composition according to the invention comprises collagen as the vehicle and at least one antiseptic and/or inflammatory substance as the active principle.Application to the topical treatment of periodontal complaints.

Abstract: The invention relates to vessel prostheses formed from a porous vascular prosthesis impregnated with diisocyanate crosslinked gelatin for sealing the pores.

Abstract: A composition which combines autogenic bone marrow with a suspension of purified atelopeptide reconstituted collagen is used to repair bone defects in mammals.

Abstract: A single lumen implantable and biocompatible breast prosthesis composed of an outer membrane of silastic, medical grade silicone, and an inner filling material selected from the group consisting of purified reconstituted collagen gel and a purified gel of poly-alpha amino acid homopolymers or random copolymers having a molecular weight of from 5,000 to 400,000. The purified reconstituted collagen gel has a collagen concentration of from 20 to 100 milligrams per milliliter of gel.

Abstract: An improved soft tissue implant which resists capsule formation and contracture is described. The implant is coated with a non-immunogenic collagen preparation optionally stabilized by crosslinking.

Abstract: A soft tissue wound healing composition comprising an aqueous mixture of fibrillar collagen, heparin, and undegranulated platelets or platelet releasate. The composition is applied topically to the wound site in conjunction with means to keep it at the site and hydrated or in the form of an occlusive dressing.

Abstract: A biomaterial suitable for use in medical devices which comprises peritoneal tissue, especially animal parietal peritoneum tissue, which has been chemically treated to crosslink the collagen in the tissue.

Abstract: This invention relates to a hemostatic agent used in surgical operations, which can be produced in two ways: one blending collagen/gelatin with protamine, the other blending collagen/gelatin with protamine and a bi-functional cross-linking agent so as to make said collagen/gelatin have a covalent bond with said protamine. The produced hemostatic agent can stop bleeding within far less time than a conventional hemostatic agent made out of pure collagen.

Abstract: Bio-and blood compatible materials are prepared by treating the surface of a substrate to provide reactive primary or secondary amine groups sites which are activated by treatment with a dialdehyde or arylchloride for coupling to a biological in an amount sufficient to provide compatibility. The use of specific substrates, such as a compliant, and elastic material, such as a fabric-elastomer membrane matrix, results in a product having advantageous qualities as a thermal burn dressing. Detailed procedures and various products are described including gloves and sleeves and tubes with or without adhesive to facilitate formation of sheet materials into various forms and products. The products may have small holes provided therein for the rapid passage of accumulated fluid away from the wound or infusion of liquid materials to the wound site.

Abstract: Collagen membranes with desired properties are prepared by using a variety of gel-forming techniques in combination with methods for converting the gels to solid forms. The properties of these membranes or other solid forms may be further altered by cross-linking the collagen preparation either after formation of the membrane or gel, or most preferably by mixing cross-linked collagen with solubilized collagen in the original mixture used to create the gel.

Abstract: Chemically-modified collagen is prepared by reacting native collagen with a di or tri-carboxylic acid halide, di or tri-sulfonyl halide, di or tri-anhydride, or di or tri-reactive active ester coupling agent. The reaction is done in a controlled manner so that the degree of cross-linking is limited. Any remaining lysine epsilon amino groups present in the coupled collagen product may be converted to carboxyamido or sulfonamido groups by acid halide, anhydride, sulfonyl halide or active ester amine-modifying agents. The resultant product when dissolved in a physiological buffer provides a viscoelastic solution having therapeutic application in a variety of surgical procedures, particularly in ophthalmic surgery. This viscoelastic solution "melts," i.e., exhibits a dramatic loss of viscosity, when subjected to temperatures of between 32.degree. and 48.degree. C.

Abstract: A method of treating a solid tumor, including the steps of localizing the tumor and the arterial vessel that supplies it, and injecting into the vessel, a vaso-occlusive collagen material adapted to produce occlusion of vessels having lumen diameters between about 10 and 150 microns. The injected material is effective to produce occlusion of the secondary and tertiary vessels supplying the tumor, distal to the collateral blood vessels which may also supply the tumor. The region of the occluded tumor is heated under conditions that produce tissue necrosis selectively in the occluded tumor tissue.

Abstract: The medical material contains heparinized collagen in which heparin has been bonded to protamine covalently fixed on collagen, and, owing to its excellent compatibility with living bodies, especially, its superb antithrombotic property, can be suitably used as a substituent material for tissues or organs which are brought into direct contact with blood, namely, as aritificial vessels, artificial valves and patching materials for cardiovascular organs, and the above medical material is also suitable as a membrane having anti-adhesion effects. The medical material is obtained by immersing and treating a natural or artificial material successively in an aqueous protamine solution, an aqueous glutaraldehyde solution and an aqueous heparin solution.

Abstract: There are disclosed processes for preparing biodegradable collagen-based matrices in sponge or sheet form wherein in one embodiment a collagen-based material including a collagen selected from the group consisting of types I, II and II collagens is freeze dried to form a collagen-based sponge which is contacted with a cross-linking agent selected from the group consisting of a carbodiimide or a succinimidyl active ester to form an intermediate collagen-based matrix which is subsequently subjected to conditions of severe dehydration to form the collagen-based matrix in sponge or sheet form. In another embodiment, a collagen-based sponge or sheet is first subjected to conditions of severe dehydration followed by contacting the thus formed intermediate collagen-based matrix with a carbodiimide crosslinking compound to form the collagen-based matrix in sponge or sheet form.

Abstract: This invention concerns a production process of an antithrombogenic and antiadhesive material which can favorably be used as artificial blood vessels, artificial valves, grafting patches for cardiovascular organs, artificial heart catheters and so on. The gist of this invention is constructed substantially of subjecting glycidyltrialkylammonium halide such as glycidyltrimethylammonium chloride to the reaction with a material comprising pure collagen or collagen and other components like mucopolysaccharide in order to introduce a cationic quaternary functional group in collagen molecules of the material and then subjecting heparin to the ionic combination with the cationic functional group introduced.

Abstract: A process for preparing collagen membranes useful in tissue repair, and wound healing and related membranous implant materials useful in both hard and soft tissue applications is disclosed. The resulting membranes and materials have properties which can be varied as desired to suit intended use. Variation results from altering the precise conditions of formation of the membrane or of related fibers and solids. The process comprises first forming a gel from solubilized collagen, followed by converting the gel into a one-, two- or three-dimensional membranous solid form. This conversion is performed either by applying pressure to the gel, or by disrupting the gel and separating the resulting precipitate for casting.

Abstract: A process for preparing collagen membranes useful in tissue repair, and wound healing and related membranous implant materials useful in both hard and soft tissue applications is disclosed. The resulting membranes and materials have properties which can be varied as desired to suit intended use. Variation results from altering the precise conditions of formation of the membrane or of related fibers and solids. The process comprises first forming a gel from solubilized collagen, followed by converting the gel into a one-, two- or three-dimensional membranous solid form. This conversion is performed either by applying pressure to the gel, or by disrupting the gel and separating the resulting precipitate for casting.

Abstract: An injectable collagen material composed of reconstituted, mechanically sheared atelopeptide collagen fibers. The material is prepared by passing reconstituted collagen fibers repeatedly through a rigid mesh screen, until a substantial reduction in fiber size and size-heterogeneity is achieved. The mechanically sheared fibers may be further crosslinked to improve implant characteristics.

Abstract: The present invention relates to a collagen gel and to a process for obtaining it. More particularly, the present invention relates to an improved homogeneous collagen gel, which can be used in the manufacture of collagen film articles of improved thinness, smoothness, superior strength, and superior homogeneity, and to a process for obtaining the improved gel.

Abstract: A process for the production of an unnative and biologically active bonded collagen fiber sheet from human placentae is described, in which process collagen-containing material from placentae is treated with a neutral salt solution, a solution of citric acid and with pepsin. The degraded collagen material obtained in this manner is, where appropriate, treated with a crosslinking agent. The collagen material produced in this manner is used for producing bonded collagen fiber sheets which can be used, for example, as covering for wounds.

Abstract: An improved hemostatic article is made by fusing an onlay of hemostatic agent to a porous body which is already impregnated with the same or with a different hemostatic agent. The hemostatic agent(s) may comprise a collagen or collagen-like substance which has been modified by rendering the surface charge thereof effectively more positive than prior to modification.

Abstract: A process for preparing collagen membranes useful in tissue repair, and wound healing and related membranous implant materials useful in both hard and soft tissue applications is disclosed. The resulting membranes and materials have properties which can be varied as desired to suit intended use. Variation results from altering the precise conditions of formation of the membrane or of related fibers and solids. The process comprises first forming a gel from solubilized collagen, followed by converting the gel into a one-, two- or three-dimensional membranous solid form. This conversion is performed either by applying pressure to the gel, or by disrupting the gel and separating the resulting precipitate for casting.

Abstract: Cross-linked atelopeptide collagen that is substantially free of residual cross-linking agent is prepared by: reconstituting atelopeptide collagen from solution by neutralizing the solution at a reduced temperature and a hypotonic ionic strength; cross-linking the reconstituted fibers in an aqueous medium at a concentration of 0.1 to 10 mg/ml with glutaraldehyde under conditions that produce cross-linked collagen that when in suspension in physiological saline at a concentration of 35 mg/ml exhibits a shear viscosity whose log varies linearly with the log of the shear rate and is approximated by the formulalog .eta..ltoreq.-0.96 log .gamma.+2.3where .gamma. is the shear rate in sec.sup.-1, log .gamma. is in the range of -6 to +2 and .eta. is the viscosity of the suspension in Pascal-sec; optionally quenching the cross-linking reaction with an amino acid; and separating the cross-linked atelopeptide collagen from the reaction mixture.

Abstract: This invention relates to a prosthetic replacement for the cornea and particularly to a transparent collagen material useful for making such a prosthesis and to methods for making such transparent collagen material. The prosthesis is preferably composed of a native, non-fibrilized, transparent collagen material formed from a soluble collagen solution by ultracentrifuging to form a pellet and fixing the same pellet, whereby the collagen material has less than 5% absorbance of light at 900 nm for a 5 mm thick sample and comprises polyhydroxyethylmethacrylate or vitrosin, in a range of from 0.01 to 50.0 percent by weight, based on the collagen protein.

Abstract: Hemostatic-adhesive, collagen dressings in the form of dry-laid, non-woven, self-supporting webs of collagen fibers and methods for preparing those webs are disclosed. The webs are formed from a mass of hemostatic-adhesive, collagen fibers having a moisture content of from about 7% to about 15% by weight, and retain the hemostatic-adhesive properties of the mass of collagen fibers.

Abstract: Catgut suturing filament protected by a flexible polymer sheath that is slowly hydrolytically degradable and impervious to body fluid degratative enzymes. The sheath is prepared by coating the catgut filament with an isocyanate capped polyhydroxylated polyester followed by curing.

Abstract: A transparent native, non-fibrilized collagen material is described having an absorbence at a wavelength of 900 nm of less than 5% in a sample 5 mm thick. This collagen material is useful for a prosthetic replacement of the cornea because of the high transparency and because it is a native material, and thus less susceptible to immunogenic responses. A method for forming the native, non-fibrilized, highly transparent collagen material comprises ultracentrifuging a purified solution of native collagen to form a pellet of transparent collagen material, and fixing the pellet of collagen material to form a rigid, leather-like material. The collagen material can also be used for prosthetic replacement of other bodily tissues, such as nucleus pulposus, cartilage, and vitreous body.

Abstract: New and highly stable preparations containing collagen in association with mucopolysaccharides are obtained by combining a homogeneous gel or solution of crosslinked or decrosslinked collagen, and a solution of CSA or CSC, and bringing the pH to 7.

Abstract: A process for preparing a crosslinked collagen-glycosaminoglycan composite material which comprises forming an uncrosslinked composite material from collagen and a glycosaminoglycan and contacting the uncrosslinked composite with a gaseous aldehyde until a crosslinked product having an M.sub.c of from about 800 to about 60,000 is disclosed along with composite materials prepared by this process. Artificial skin produced by this process is more stable toward long-term storage than similar materials prepared using other methods of crosslinking.

Abstract: A process for preparing a coherent porous collagen sheet material is comprised of forming natural insoluble particulate collagen in substantially pure form and suspending the particulate collagen in a weak aqueous organic acid solution while maintaining the collagen in particulate form. The suspension is freeze-dried to form a coherent porous native collagen sheet material which is useful as a wound dressing, burn dressing, hemostatic sheet or the like.

Abstract: The invention comprises a bio-compatible composition suitable for constructing surgical articles for the repair or replacement of a part of the body of a human or non-human animal, e.g., ligaments, tendons, bones, comprising a composite of a bio-absorbable polymer and at least one substrate of a plurality of carbon fibers.The invention also includes surgical articles fabricated from the composites for the repair of damaged tissue, e.g., tendons, ligaments and bones.The invention includes a method for the formation of the aforesaid composite comprising providing a substrate of the carbon fibers and providing the substrate with a continuous coating of a bio-absorbable polymer.The invention also includes the surgical repair of a damaged body part such as a ligament, tendon or bone comprising surgically affixing to the damaged part the surgical article, the bio-absorbable polymer being absorbed by the body upon formation of the new tissue.

Abstract: An improved hemostatic article is made by combining collagen or a collagen-like substance with a pad or sponge. The thusly modified pad or sponge is employed to control or terminate bleeding.

Abstract: An improved hemostatic article is made by combining collagen or a collagen-like substance with a pad or sponge. The thusly modified pad or sponge is employed to control or terminate bleeding.