Membrane for use in guided tissue regeneration

Abstract

The invention provides a multi-layer membrane comprising a matrix layer predominantly of collagen II and having an open sponge-like texture, and at least one barrier layer having a close, relatively impermeable texture. Such a membrane is particularly suitable for use in guided tissue regeneration, in particular for use in vivo in the reconstruction of bone or cartilage tissue.

1 . A membrane comprising a resorbable multi-layer membrane for use in vivo in the reconstruction of bone or cartilage tissue, said resorbable multi-layer membrane comprising a matrix layer having a matrix consisting essentially of collagen II and having an open sponge-like texture, and at least one barrier layer having a close, relatively impermeable texture, the at least one barrier layer consisting essentially of a barrier layer material selected from the group consisting of collagen I, collagen III and a mixture thereof, wherein said multi-layer membrane is formed by adhering of said matrix layer to said at least one barrier layer by non-sutured adhesive, so that said matrix layer is adhered firmly to and in direct contact with said at least one barrier layer.  
     
     
         2 . A membrane as claimed in  claim 1  in which the matrix layer is provided between two barrier layers.  
     
     
         3 . A membrane as claimed in  claim 1  in which the matrix layer is provided by collagen II material derived from natural cartilage.  
     
     
         4 . A membrane as claimed in  claim 3  wherein the collagen II material is derived from hyaline cartilage from pigs.  
     
     
         5 . A membrane as claimed in  claim 3  in which the collagen II material is physically cross-linked.  
     
     
         6 . A membrane as claimed in  claim 4  in which the at least one barrier layer is derived from peritoneum membrane from calves or pigs.  
     
     
         7 . A membrane as claimed in  claim 1  in which the matrix layer is impregnated with chondrocytes isolated from articular cartilage, periosteum, periocardium or mesenchymal stem cells from bone marrow.  
     
     
         8 . A membrane as claimed in  claim 1  in which the matrix layer, said at least one barrier layer, or each said layer is impregnated with a glycosaminoglycan.  
     
     
         9 . A membrane as claimed in  claim 8  wherein the glycosaminoglycan is hyaluronic acid, chondroitin 6-sulphate, keratin sulphate or dermatan sulphate.  
     
     
         10 . A membrane as claimed in  claim 1  in which the matrix and barrier layers are substantially free from proteoglycans.  
     
     
         11 . A membrane as claimed in  claim 1  in which the matrix layer, said at least one barrier layer, or each of the layers further comprise chondronectin, lectin, fibronectin, calcium alginate, anchorin II, growth factors or bone morphogenetic factors.  
     
     
         12 . A process for the preparation of a membrane as claimed in  claim 1  in which a collagen II slurry is applied to a surface of a barrier membrane having a close, relatively impermeable texture, followed by freeze-drying whereby to provide a matrix layer having an open sponge-like structure.  
     
     
         13 . A method of treating a bone or cartilage defect in the human or non-human animal body, said method comprising application of a membrane as claimed in  claim 1  to the defect, said membrane being oriented such that the barrier layer or layers prevent the ingrowth of undesirable tissue types into the area of bone or cartilage regeneration.  
     
     
         14 . A method of treating a bone or cartilage defect in the human or non-human animal body, said method comprising application of a membrane as claimed in  claim 1  to the defect, said membrane being oriented such that the barrier layer or layers prevent the ingrowth of undesirable tissue types into the area of bone or cartilage regeneration, and wherein the matrix layer of said membrane is impregnated with chondrocytes either immediately prior to or following application to the defect.  
     
     
         15 . The method of  claim 13  wherein said membrane is applied during arthroscopic surgery.  
     
     
         16 . The method of  claim 14  wherein said membrane is applied during arthroscopic surgery.  
     
     
         17 . A membrane as claimed in  claim 11  wherein the growth factors are cartilage inducing factor (CTF), insulin-like growth factor (IGF), or transforming growth factor (TGF ).  
     
     
         18 . A membrane as claimed in  claim 11  wherein the bone morphogenetic factors are human BMP-2, BMP-3, BMP-4 or BMP-7.  
     
     
         19 . A membrane comprising a resorbable multi-layer membrane for use in vivo in the reconstruction of bone or cartilage tissue at a site of a defect in said tissue, said resorbable multi-layer membrane comprising a matrix layer having a matrix comprising collagen I, collagen III or a mixture thereof, and having an open sponge-like texture, and at least one barrier layer having a close, relatively impermeable texture, the at least one barrier layer comprising a barrier layer comprising collagen I, collagen III or a mixture thereof, wherein said multi-layer membrane is formed by application of said matrix layer to said at least one barrier layer as a slurry, so that said matrix layer is adhered firmly to and in direct contact with said at least one barrier layer, wherein firm adherence of the matrix layer to said at least one barrier layer results essentially solely from application of said slurry to said at least one barrier layer.  
     
     
         20 . A membrane comprising a resorbable multi-layer membrane for use in vivo in the reconstruction of bone or cartilage tissue at a site of a defect in said tissue, said resorbable multi-layer membrane comprising a matrix layer having a matrix comprising collagen I, collagen II or a mixture thereof, and having an open sponge-like texture, and at least one barrier layer having a close, relatively impermeable texture, the at least one barrier layer comprising collagen I, collagen III or a mixture thereof, wherein said multi-layer membrane is formed by application of said matrix layer to said at least one barrier layer by non-sutured adhesive, so that said matrix layer is adhered firmly to and in direct contact with said at least one barrier layer.