In situ bioprosthetic filler and methods, particularly for the in situ formation of vertebral disc bioprosthetics

Abstract

Bioprosthetic devices include an exterior biological tissue member which at least partly defines a cavity, and a proteinaceous biopolymer which fills the cavity, and intercalates and is chemically bound (fixed) to the tissue of the surrounding biological tissue member. In preferred forms, the bioprosthetic device is a bioprosthetic vertebral disc having a fibrillar outer annulus which surrounds and defines an interior cavity and is formed by removal of at least a substantial portion of the natural gelatinous core therefrom. The cavity defined by the fibrillar outer annulus may then be filled with a flowable proteinaceous biopolymer. Preferably, the proteinaceous biopolymer is a liquid mixture comprised of human or animal-derived protein material and a di- or polyaldehyde, which are allowed to react in situ to form a cross-linked biopolymer within the cavity. The liquid mixture may be formed in advance of being introduced into the cavity, or may be formed simultaneously during introduction into the cavity.

What is claimed is:  
     
         1 . The combination comprised of an exterior biological tissue member which at least partly defines a cavity, and a polymeric material which fills the cavity, intercalates the surrounding biological tissue member, and is chemically bound to the tissue of the surrounding biological tissue member.  
     
     
         2 . The combination of  claim 1 , wherein the polymeric material is a proteinaceous biopolymer.  
     
     
         3 . The combination of  claim 1 , wherein the polymeric material includes a fibrous or particulate filler material.  
     
     
         4 . The combination of  claim 2 , wherein the biopolymer is the cross-linked reaction product of human or animal-derived protein material and a di- or polyaldehyde.  
     
     
         5 . The combination of  claim 4 , wherein the protein is bovine or human serum albumin or hemoglobin.  
     
     
         6 . The combination of  claim 5 , wherein the aldehyde is glutaraldehyde.  
     
     
         7 . The combination of any one of claims  1 - 6 , in the form of a vertebral disc.  
     
     
         8 . The combination of  claim 7 , wherein the vertebral disc which remains intact and flexible after being subjected to 5 million cycles of a cyclic load of 0.85 MPa.  
     
     
         9 . The combination of  claim 2 , wherein the proteinaceous biopolymer is the reaction product of at least two reactable components, and wherein one of the components includes a natural, synthetic or sequence-modified polypeptide.  
     
     
         10 . The combination of  claim 1 , wherein the polymeric material is the reaction product of at least two reactable components, and wherein one of the components includes a synthetic polymeric component which contains a cross-linkable functional group.  
     
     
         11 . The combination of  claim 10 , wherein the synthetic polymeric components includes polyethylene glycol polymer derivatized with electrophilic and/or nucleophilic groups.  
     
     
         12 . The combination of  claim 11 , wherein the electrophilic and/or nucleophilic groups include at least one selected from amine, succinimidyl, anhydride and thiol groups.  
     
     
         13 . A bioprosthetic vertebral disc comprised of a fibrillar outer annulus which remains following removal of a gelatinous core from a biologically natural vertebral disc to thereby define an interior cavity, and a proteinaceous biopolymer which fills the cavity and intercalates the surrounding biological tissue of the fibrillar outer annulus.  
     
     
         14 . The bioprosthetic vertebral disc of  claim 13 , that exhibits flexibility comparable to the biologically natural vertebral disc.  
     
     
         15 . The bioprosthetic vertebral disc of  claim 14 , that exhibits flexibility comparable to the biologically natural vertebral disc after being subjected to 5 million cycles of a cyclic load of 0.85 MPa.  
     
     
         16 . The bioprosthetic vertebral disc of  claim 14 , wherein the biopolymer includes a fibrous or particulate filler material.  
     
     
         17 . The bioprosthetic vertebral disc of  claim 13 , wherein the biopolymer is the cross-linked reaction product of human or animal-derived protein material and a di- or polyaldehyde.  
     
     
         18 . The bioprosthetic vertebral disc of  claim 17 , wherein the protein is bovine or human serum albumin or hemoglobin.  
     
     
         19 . The bioprosthetic vertebral disc of  claim 17  or  18 , wherein the aldehyde is glutaraldehyde.  
     
     
         20 . A method for the in situ formation of a bioprosthetic device comprising filling a cavity defined at least partly by surrounding biological tissue material with a flowable polymeric material in situ within the cavity thereby forming the bioprosthetic device.  
     
     
         21 . The method of  claim 20 , which comprises injecting a flowable proteinaceous biopolymer into the cavity, and allowing the proteinaceous biopolymer to at least partly solidify in situ therewithin.  
     
     
         22 . The method of  claim 20 , said method comprises injecting at least two reactable biopolymeric components in situ within the cavity, and allowing the reactable biopolymeric components at least partly solidify by a cross-linkage reaction therebetween.  
     
     
         23 . The method of  claim 21 , wherein said at least two reactable components are premixed before being injected into the cavity.  
     
     
         24 . The method of  claim 21 , wherein said at least two reactable components are mixed simultaneously while being injected into the cavity.  
     
     
         25 . The method of  claim 21 , wherein said at least two reactable components include a liquid mixture comprised of human or animal-derived protein material and a di- or polyaldehyde, and wherein the method comprises allowing the liquid mixture to form a cross-linked proteinaceous biopolymer material in situ within the cavity.  
     
     
         26 . The method of  claim 25 , wherein said protein material and said di- or polyaldehyde are premixed before being introduced into the cavity.  
     
     
         27 . The method of  claim 25 , wherein said protein material and said di- or polyaldehyde are mixed simultaneously while being introduced into the cavity.  
     
     
         28 . The method of  claim 25 , which includes providing a fibrous or particulate filler material in the liquid mixture.  
     
     
         29 . The method of  claim 21 , wherein the proteinaceous biopolymer is the reaction product of at least two reactable components, and wherein one of the components includes a natural, synthetic or sequence-modified polypeptide.  
     
     
         30 . The method of  claim 20 , wherein the polymeric material is the reaction product of at least two reactable components, and wherein one of the components includes a synthetic polymeric component which contains a cross-linkable functional group.  
     
     
         31 . The method of  claim 30 , wherein the at least one of the reactable components includes polyethylene glycol polymer derivatized with electrophilic and/or nucleophilic groups.  
     
     
         32 . The method of  claim 31 , wherein the electrophilic and/or nucleophilic groups include at least one selected from amine, succinimidyl, anhydride and thiol groups.  
     
     
         33 . A method for the formation of a bioprosthetic vertebral disc comprising: 
 (a) providing a vertebral disc having a fibrillar outer annulus which surrounds and defines an interior cavity formed by removal of at least a substantial portion of a gelatinous core therefrom;    (b) filling the cavity defined by the fibrillar outer annulus with a flowable polymeric material, and    (c) allowing the polymeric material to at least partly solidify in situ within the cavity.    
     
     
         34 . The method of  claim 33 , wherein the polymeric material is a proteinaceous biopolymer.  
     
     
         35 . The method of  claim 33 , said method comprises injecting at least two reactable biopolymeric components in situ within the cavity, and allowing the reactable biopolymeric components at least partly solidify by reaction therebetween.  
     
     
         36 . The method of  claim 35 , wherein said at least two reactable components are premixed before being injected into the cavity.  
     
     
         37 . The method of  claim 35 , wherein said at least two reactable components are mixed simultaneously while being injected into the cavity.  
     
     
         38 . The method of  claim 35 , wherein said at least two reactable components include a liquid mixture comprised of human or animal-derived protein material and a di- or polyaldehyde, and wherein the method comprises allowing the liquid mixture to form a cross-linked proteinaceous biopolymer material in situ within the cavity.  
     
     
         39 . The method of  claim 38 , wherein said protein material and said di- or polyaldehyde are premixed before being introduced into the cavity.  
     
     
         40 . The method of  claim 38 , wherein said protein material and said di- or polyaldehyde are mixed simultaneously while being introduced into the cavity.  
     
     
         41 . The method of  claim 38 , which includes providing a fibrous or particulate filler material in the liquid mixture.  
     
     
         42 . The method of  claim 33 , wherein prior to step (a) there is practiced the step of (a1) removing a substantial portion of the gelatinous core of the vertebral disc to leave the fibrillar outer annulus which defines the interior cavity.