Abstract: Non-glutaraldehyde fixation of an organ or a prosthesis for implantation in a mammal is based upon carbodiimide treatment. A solution containing a sterilizing agent, such as EDC, in combination with a coupling enhancer, such as Sulfo-NHS, and a high concentration of a diamine cross linking agent is used. As a result, only minimal surface reduction occurs during fixation, and the resultant products show a dramatic increase in resistance to calcification.

Abstract: Non-glutaraldehyde fixation of an organ or a prosthesis for implantation in a mammal is based upon carbodiimide treatment. An aqueous solution containing a coupling agent, such as EDC, in combination with a coupling enhancer, such as sulfo-NHS, and a high concentration of a diamine cross-linking agent is used. As a result, only minimal surface reduction occurs during fixation, and the resultant products show a dramatic increase in resistance to calcification.

Abstract: Non-glutaraldehyde fixation of an organ or a prosthesis for implantation in a mammal is based upon carbodiimide treatment. An aqueous solution containing a coupling agent, such as EDC, in combination with a coupling enhancer, such as sulfo-NHS, and a high concentration of a diamine cross-linking agent is used. As a result, only minimal surface reduction occurs during fixation, and the resultant products show a dramatic increase in resistance to calcification.

Abstract: Allograft tissue prostheses, as well as tissue valves for replacement of defective heart valves and other tissue-engineered products (TEPs), are effectively sterilized by treatment with a coupling agent known to create amide linkages between amines and carboxylic acids in the presence of a protecting agent. The sterilization treatment preferably employs EDC as a water-soluble coupling agent, plus a water-soluble protecting agent which complexes with potentially reactive amine or carboxyl moieties on the biological tissue, in the optional presence of isopropanol or an equivalent alkanol. One preferred sterilization treatment process uses a buffered aqueous solution where a hydroxymonoamine buffer, such as TRIS plus ethanolamine, provides both the buffering effect and the protecting agents, effectively complexing with potentially reactive carboxyl moieties on the tissue.

Abstract: Heart valves or other components for replacement of heart or other bodily organs and tissue prostheses or synthetic prosthetic materials are effectively sterilized by treatment with a carbodiimide coupling agent known to create amide linkages between amines and carboxylic acids. Such treatment has been shown to be bactericidal when carried out using an effective concentration of such a carbodiimide at a temperature of at least about 35° C. for a sufficient period of time, e.g. treatment for about 9 hours at a concentration of at least about 50 mM. The sterilization treatment preferably employs EDC as a water-soluble coupling agent.

Abstract: Heart valves or other components for replacement of heart or other bodily organs and tissue prostheses or synthetic prosthetic materials are effectively sterilized by treatment with a coupling agent known to create amide linkages between amines and carboxylic acids in the presence of a lower alkanol. Such treatment has been shown to be bactericidal when carried out at 40.degree. C. for over 1 hour. The sterilization treatment preferably employs EDC as a water-soluble coupling agent plus an optional coupling enhancer such as sulfo-NHS or NHS, in the presence of isopropanol or an equivalent alkanol. Such sterilization treatment is preferably carried out at a temperature above ambient temperature in a buffered aqueous solution. The treatment leaves no residuals other than ones which are nontoxic and biocompatible, does not affect the resistance of the tissue to thermal denaturation and to digestion by proteolytic enzymes, and surprisingly also increases the resistance of fixed biological tissue to calcification.

Abstract: A process is provided for non-glutaraldehyde fixation of an organ or prosthesis to be implanted in a mammal. The process produces stable fixation of the tissue by forming amide linkages within and between the molecules of the tissue and employs a coupling agent, such as EDC, in combination with a coupling enhancer, such as Sulfo-NHS; diamine and/or dicarboxyl cross-linking agents are optionally included. In addition to fixing the tissue, the process prevents or retards calcification and results in a nontoxic product that does not cause inflammation.

Abstract: A process is provided for the non-glutaraldehyde fixation of a prosthesis to be implanted in a mammal whereby the prosthesis is fixed by employing cross-linking agents to form amide linkages between and within the molecules of the prosthetic tissue. The disclosed process prevents or retards calcification and results in a product which does not cause inflammation and is nontoxic; it thus provides prostheses that are well-suited for implantation in a mammal.

Abstract: A method for retarding or preventing the calcification of a prosthesis implanted in a mammal by covalently coupling to the prosthesis before implantation an effective amount of an anticalcification agent in the form of an aliphatic carboxylic acid, or a derivative thereof, which contains from about 8 to about 30 carbon atoms and which may be straight-chain or branched-chain and saturated or unsaturated. Such acid is substituted by at least one amino, mercapto, carboxyl or hydroxyl group by which the covalent coupling takes place. For a natural tissue prosthesis, such coupling may be to an aldehyde group of gluteraldehyde in which the tissue is pre-soaked.