Tissue repair fabric

Abstract

This invention is directed to prosthesis, which, when implanted into a mammalian patient, serves as a functioning replacement for a body part, or tissue structure, and will undergo controlled biodegradation occurring concomitantly with bioremodeling by the patient's living cells. The prosthesis is treated so that it is rendered non-antigenic so as not to elicit a significant humoral immune response. The prosthesis of this invention, in its various embodiments, thus has dual properties. First, it functions as a substitute body part, and second, it functions as bioremodeling template for the ingrowth of host cells.

What is claimed:  
     
         1 . A prosthesis comprising two or more superimposed, bonded layers of collagenous tissue which have been crosslinked with a crosslinking agent that permits bioremodeling and sterilized, wherein all of the layers of the prosthesis are completely bioremodelable, and which, when implanted into a mammalian patient, undergoes controlled biodegradation occurring with adequate living cell replacement such that the original implanted prosthesis is remodeled by the patient's living cells.  
     
     
         2 . The prosthesis of  claim 1  wherein the shape of said prosthesis is flat, tubular, or complex.  
     
     
         3 . The prosthesis of  claim 1  wherein said collagen material is sourced from a mammalian source and is intestinal material, fascia lata, dura mater, and pericardium.  
     
     
         4 . The prosthesis of  claim 3  wherein said collagen material is the tunica submucosa of the small intestine.  
     
     
         5 . The prosthesis of  claim 1  wherein said collagen layers are bonded together by heat welding for a time and under conditions sufficient to effect the bonding of the collagenous tissue layers.  
     
     
         6 . The prosthesis of  claim 1  wherein said prosthesis is crosslinked with the crosslinking agent 1-ethyl-3-(3-dimethylaminopropyl) carbodiimide hydrochloride.  
     
     
         7 . The prosthesis of  claim 6  wherein sulfo-N-hydroxysuccinimide is added to the crosslinking agent.  
     
     
         8 . The prosthesis of  claim 6  wherein acetone is added to the crosslinking agent.  
     
     
         9 . The prosthesis of  claim 1  wherein the prosthesis is sterilized with peracetic acid.  
     
     
         10 . The prosthesis of  claim 10  wherein said prosthesis is non-antigenic.  
     
     
         11 . The prosthesis of  claim 1  wherein one or more surfaces of said prosthesis is coated with a collagenous material which acts as a smooth flow surface.  
     
     
         12 . The prosthesis of  claim 1  wherein said prosthesis further contains pores.  
     
     
         13 . The prosthesis of  claim 1  wherein said prosthesis is further composed of chopped collagen fibers.  
     
     
         14 . The prosthesis of  claim 1  wherein said prosthesis is further composed of collagen threads.  
     
     
         15 . The prosthesis of  claim 14  wherein said collagen threads are arranged to form a felt, a bundle, a weave or a braid.  
     
     
         16 . The prosthesis of any of claims  13 - 15  wherein said collagen fibers or threads are partially or completely crosslinked.  
     
     
         17 . The prosthesis of  claim 1  wherein said prosthesis additionally contains an anticoagulant; one or more antibiotics, or one or more growth factors.  
     
     
         18 . A method of preparing a prosthesis having two or more superimposed, bonded layers of collagen material, comprising: 
 (a) bonding the two or more collagen layers together using heat welding by heating said collagenous tissue layers for a time and under conditions sufficient to effect the bonding of the collagen layers and to form a prosthesis;    (b) cooling said heated prosthesis; and,    (c) crosslinking said prosthesis with a crosslinking agent that permits bioremodeling, wherein said thus formed prosthesis when implanted into a mammalian patient, undergoes controlled biodegradation occurring with adequate living cell replacement such that the original implanted prosthesis is remodeled by the patient's living cells;    wherein the collagenous tissue layers are sterilized with peracetic acid before bonding in step (a) or the prosthesis is sterilized after crosslinking in step (c).    
     
     
         19 . The method of  claim 18  wherein said collagen layers are formed from two or more layers of collagenous tissue sourced from a mammalian source and is intestinal material, fascia lata, dura mater, and pericardium.  
     
     
         20 . The method of  claim 19  wherein said collagen material is the tunica submucosa of the small intestine.  
     
     
         21 . The method of  claim 18  wherein said heat welding is from about 50° C. to about 75° C., more preferably from about 60° to 65° C. and most preferably at about 62° C.  
     
     
         22 . The method of  claim 18  wherein said cooling is accomplished by quenching.  
     
     
         23 . The method of  claim 18  wherein said heat welding is accomplished for a time from about 7 minutes to about 24 hours, preferably about 1 hour.  
     
     
         24 . The method of  claim 18  wherein said prosthesis is crosslinked with the crosslinking agent 1-ethyl-3-(3-dimethylaminopropyl) carbodimide hydrochloride.  
     
     
         25 . The method of  claim 18  wherein said prosthesis is non-antigenic.  
     
     
         26 . A method of repairing or replacing a damaged tissue comprising implanting a prosthesis in a patient comprising two or more superimposed, bonded layers of collagenous tissue which have been sterilized with peracetic acid and crosslinked with a crosslinking agent that permits bioremodeling, wherein all of the layers of the prosthesis are completely bioremodelable, and which, when implanted into a mammalian patient, undergoes controlled biodegradation occurring with adequate living cell replacement such that the original implanted prosthesis is remodeled by the patient's living cells.  
     
     
         27 . A sterile, non-pyrogenic, and non-antigenic prosthesis formed from mammalian derived collagenous tissue for engraftment to a recipient patient, whereby said engrafted prosthesis does not elicit a humoral immune response to components in said collagenous tissue and wherein said prosthesis concomitantly undergoes bioremodeling occurring with adequate living cell replacement such that the original implanted prosthesis is remodeled by the patient's living cells.  
     
     
         28 . The prosthesis if  claim 27  wherein said humoral immune response to components derived from said collagenous tissue demonstrates no significant increase in antibody titer for antibodies from baseline titer levels when blood serum obtained from a recipient of a prosthesis is tested for antibodies to proteins in extracts of the collagenous tissue..  
     
     
         29 . The prosthesis of  claim 28  wherein said antibody titer levels is 1:40 or less for a patient or host previously non-sensitized to collagenous tissue proteins.  
     
     
         30 . A method of preparing a non-antigenic prosthesis prepared from collagenous tissue derived from a mammalian source selected from the group consisting of intestinal material, fascia lata, dura mater, and pericardium, comprising: 
 (a) disinfecting the collagen material with peracetic acid at a concentration between about 0.01 and 0.3% v/v in water; and,    (b) crosslinking said sterilized collagenous tissue with a crosslinking agent that permits bioremodeling;    wherein the prosthesis isformed from two or more superimposed, bonded layers of collagenous tissue, wherein all of the layers of the prosthesis are bioremodelable, and wherein the prosthesis when implanted into a mammalian patient, undergoes controlled bioremodeling occurring with adequate living cell replacement such that the original implanted prosthesis is remodeled by the patient's living cells without eliciting a significant humoral immune response.    
     
     
         31 . The method of  claim 30  wherein said collagenous tissue is the tunica submucosa of the small intestine.  
     
     
         32 . The method of  claim 30  wherein said collagen material is formed from two or more layers of superimposed, bonded layers of collagen material.  
     
     
         33 . The method of  claim 30  wherein the prosthesis is sterilized with peracetic acid prior to implantation into the mammalian patient.