Biocompatible tissue sealant for treatment of osteochondral and bone defects using an acellular matrix implant

Abstract

An acellular matrix implant for treatment of defects and injuries of articular cartilage, bone or osteochondral bone and a method for treatment of injured, damaged, diseased or aged articular cartilage or bone, using the acellular matrix implant implanted into a joint cartilage lesion in situ and a bone-inducing composition implanted into an osteochondral or bone defect. A method for repair and restoration of the injured, damaged, diseased or aged cartilage or bone into its full functionality by implanting the acellular matrix implant between two layers of biologically acceptable sealants and/or the bone-inducing composition into the osteochondral bone or skeletal bone defect. A method for fabrication of the acellular matrix implant of the invention. A method for preparation of bone-inducing composition.

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       32 . A biocompatible and biodegradable tissue sealant suitable for treatment of a cartilage and bone lesion using an acellular matrix implant wherein said sealant is used for sealing of a top and bottom of the cartilage or bone lesion implanted with the acellular implant, wherein said sealant is a polymer rapidly gelling from a flowable liquid or paste to a load-bearing gel within 30 seconds to 5 minutes.  
   
   
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       34 . The sealant of  claim 34  having a minimal peel strengths of at least about 3N/m to about to 30 N/m, a cohesive strength, measured as tensile strength, in the range of from about 0.2 MPa to about 1.0 MPa, or wherein said sealant has a bond strength of at least 0.5 N/cm 2  to about 6 N/cm 2 .  
   
   
       35 . The sealant of  claim 34  wherein said sealant is a gel having a cohesive strength dependent on the number of inter-chain linkages.  
   
   
       36 . The sealant of  claim 35  which has adhesive or peel strengths at least 10 N/m and tensile strength at least 0.3 MPa.  
   
   
       37 . The sealant of  claim 35  which has adhesive or peel strength of 100 N/cm and tensile strength in the range from 0.8 to 1.0 MPA.  
   
   
       38 . The sealant of  claim 36  wherein said sealant deposited at the top and the bottom of the cartilage or bone lesion is the same.  
   
   
       39 . The sealant of  claim 36  wherein said sealant deposited at the top and the bottom of the cartilage or bone lesion is different.  
   
   
       40 . The sealant of  claim 32  wherein said sealant gels from a flowable liquid or paste to a load-bearing gel within 30 seconds.  
   
   
       41 . The sealant of  claim 32  wherein said sealant is natural or synthetic.  
   
   
       42 . The sealant of  claim 41  wherein said sealant comprises a compound selected from the group of consisting of gelatin, di-aldehyde starch, 4-armed pentaerythritol tetra-thiol, polyethylene glycol diacrylate, photo-polymerizable polyethylene glycol-co-poly(α-hydroxy acid), diacrylate macromer, periodate-oxidized gelatin, serum albumin, a di-functional polyethylene glycol derivatized with maleimidyl, a di-functional polyethylene glycolderivatized with succinimidyl, a di-functional polyethylene glycolderivatized with phthalimidyl, a copolymer of polyethylene glycol and polylactide, polyglycolide, polyhydroxybutyrate, a polymer of aromatic organic amino acids, 4-armed pentaerythritol thiol, 4-armed polyethylene glycol derivatized with succinimidyl ester and thiol, albumin and methylated collagen.  
   
   
       43 . The sealant of  claim 42  wherein the sealant comprises methylated collagen.  
   
   
       44 . The sealant of  claim 43  wherein the sealant is conjugated with a cross-linking agent.  
   
   
       45 . The sealant of  claim 42  wherein said sealant comprises albumin.  
   
   
       46 . The sealant of  claim 45  wherein said albumin is human or bovine albumine conjugated with a cross-linking agent.  
   
   
       47 . The sealant of  claim 44  wherein said cross-linking agent is selected from the group consisting of glutaradehyde, amino acid, polypeptide and protein.  
   
   
       48 . The sealant of  claim 46  wherein said cross-linking agent is selected from the group consisting of glutaradehyde, amino acid, polypeptide, protein or collagen.