Method for the manufacture of an implantable cartilaginous tissue repair device

Abstract

A cartilaginous tissue repair device with a biocompatible, bioresorbable three-dimensional silk or other fibre lay and a biocompatible, bioresorbable substantially porous silk-based or other hydrogel partially or substantially filling the interstices of the fibre lay; with or without an integral means of firmly anchoring the device to a patient's hone.

1 - 19 . (canceled) 
     
     
         20 . A method for the manufacture of an implantable cartilaginous tissue repair device comprising the steps of:
 forming a three-dimensional fibre lay from biocompatible and at least partially bioresorbable silk fibres by one or more of the methods selected from the group consisting of: winding, weaving, compressing felts, twisting, knitting, braiding, stitching, embroidery, and combining layers of cloth;   preparing a biocompatible and at least partially bioresorbable, substantially porous hydrogel comprising silk protein; and   either during or after production of said three-dimensional fibre lay, infiltrating said three-dimensional fibre lay with said biocompatible and at least partially bioresorbable, substantially porous hydrogel.   
     
     
         21 . A method for the manufacture of an implantable cartilaginous tissue repair device according to  claim 20  further comprising a step of:
 cross-linking said three-dimensional fibre lay and/or cross-linking said substantially porous hydrogel. 
 
     
     
         22 . A method for the manufacture of an implantable cartilaginous tissue repair device according to  claim 20  further comprising a step of:
 treating said three-dimensional fibre lay and/or said substantially porous hydrogel with a hydrophobic acylating agent. 
 
     
     
         23 . A method for the manufacture of an implantable cartilaginous tissue repair device according to  claim 20  in which said step of preparing a porous hydrogel comprises the substeps of:
 preparing a solution of degummed silk; 
 gelling said solution of degummed silk; and 
 freezing the resulting gel of degummed silk. 
 
     
     
         24 . A method for the manufacture of an implantable cartilaginous tissue repair device according to  claim 20  which further comprises a step of mineralising a surface layer, extension or flange of said implantable cartilaginous tissue repair device. 
     
     
         25 . A method for the manufacture of an implantable cartilaginous tissue repair device according to  claim 24  in which said step of mineralising a surface layer, extension or flange of said implantable cartilaginous tissue repair device comprises the substeps of:
 preparing a buffered phosphate solution; 
 adding said buffered phosphate solution to the hydrogel which is to be contained within said surface layer, extension or flange of said implantable cartilaginous tissue repair device; 
 controlled freezing and/or drying of said surface layer, extension or flange of said implantable cartilaginous tissue repair device; and 
 exposing said surface layer, extension or flange of said implantable cartilaginous tissue repair device to a buffered calcium chloride solution. 
 
     
     
         26 . A method for the manufacture of an implantable cartilaginous tissue repair device according to  claim 25  in which said buffered phosphate solution is added to the hydrogel by utilising said buffered phosphate solution in gelling the hydrogel. 
     
     
         27 . A method for the manufacture of an implantable tissue repair device comprising the steps of:
 forming a three-dimensional fibre lay from biocompatible and at least partially bioresorbable silk fibres by one or more of the methods selected from the group consisting of: winding, weaving, compressing felts, twisting, knitting, braiding, stitching, embroidery, and combining layers of cloth;   preparing a biocompatible and at least partially bioresorbable hydrogel comprising silk protein;   either during or after production of said three-dimensional fibre lay, infiltrating said three-dimensional fibre lay with said biocompatible and at least partially bioresorbable hydrogel; and   mineralising at least one surface of said implantable tissue repair device by:
 preparing a buffered phosphate solution; 
 adding said buffered phosphate solution to the hydrogel contained within said surface of said implantable tissue repair device; 
 controlled freezing and/or drying of said surface of said implantable tissue repair device; and 
 exposing said surface of said implantable tissue repair device to a buffered calcium chloride solution. 
   
     
     
         28 . A method for the manufacture of an implantable tissue repair device according to  claim 27  in which said buffered phosphate solution is added to the hydrogel by utilising said buffered phosphate solution in gelling the hydrogel. 
     
     
         29 - 30 . (canceled) 
     
     
         31 . A method for the manufacture of an implantable tissue repair device comprising the steps of:
 preparing a biocompatible and at least partially bioresorbable hydrogel comprising silk protein; and   mineralising said hydrogel by:
 preparing a buffered phosphate solution; 
 adding said buffered phosphate solution to the hydrogel; 
 controlled freezing and/or drying of said hydrogel; 
 exposing said hydrogel to a buffered calcium chloride solution. 
   
     
     
         32 . A method for the manufacture of an implantable tissue repair device according to  claim 31  in which said buffered phosphate solution is added to the hydrogel by utilising said buffered phosphate solution in gelling the hydrogel. 
     
     
         33 . A method for the manufacture of an implantable tissue repair device according to  claim 20  wherein said three-dimensional fibre lay is substantially biomimetic of the fibre patter of a cartilaginous tissue which is to be repaired. 
     
     
         34 . A method for the manufacture of an implantable tissue repair device according to  claim 20  wherein the three-dimensional fibre lay comprises fibres selected from the group consisting of: natural mulberry-silk fibres, natural wild-silk fibres, spider-silk fibres, fibres of a recombinant protein based substantially on the proteins of mulberry silk, fibres of a recombinant protein based substantially on the proteins of wild silk, and fibres of a recombinant protein based substantially on the proteins of spider silk. 
     
     
         35 . A method for the manufacture of an implantable tissue repair device according to  claim 20  wherein said substantially porous hydrogel comprises at least one component selected from the group consisting of: regenerated silk fibroin from mulberry silk and regenerated silk fibroin from wild silk. 
     
     
         36 . A method for the manufacture of an implantable tissue repair device according to  claim 20  wherein the average pore diameter of the porous hydrogel is between 50 μm and 300 μm.