Plasticized bone and soft tissue grafts and methods of making and using same

Abstract

The present invention provides a plasticized dehydrated or freeze-dried bone and/or soft tissue product that does not require special conditions of storage, for example refrigeration or freezing, exhibits materials properties that approximate those properties present in normal hydrated tissue, is not brittle, does not necessitate rehydration prior to clinical implantation and is not a potential source for disease transmission. The invention replaces water in the molecular structure of the bone or soft tissue matrix with one or more plasticizers allowing for dehydration of the tissue, yet not resulting in an increase in brittleness of the plasticized product, and resulting in compressive and/or tensile properties similar to those of normal hydrated bone. Replacement of the chemical plasticizers by water prior to implantation is not required and thus, the dehydrated bone or soft tissue plasticized product can be placed directly into an implant site without significant preparation in the operating room.

1 . A plasticized bone graft, comprising: a cleaned bone graft comprising one or more plasticizers.  
     
     
         2 . A plasticized bone graft suitable for transplantation into a human, comprising: a bone graft having an internal matrix essentially free from bone marrow elements; and one or more plasticizers contained in said internal matrix.  
     
     
         3 . A plasticized bone graft, comprising: a cleaned bone graft; and one or more plasticizers, wherein said cleaned bone graft is impregnated with said one or more plasticizers.  
     
     
         4 . The bone graft of any one of claims  1 ,  2 , or  3 , wherein said bone graft is suitable for direct transplant into a human without rehydration.  
     
     
         5 . The bone graft of any one of claims  1 ,  2 , or  3 , wherein said bone graft is a non-demineralized bone graft.  
     
     
         6 . The bone graft of any one of claims  1 ,  2 , or  3 , wherein said bone graft is a load-bearing bone graft.  
     
     
         7 . The bone graft of any one of claims  1 ,  2 , or  3 , wherein said bone graft is a non load-bearing bone graft.  
     
     
         8 . A method for producing a plasticized bone graft suitable for transplantation into a human, comprising: impregnating a cleaned bone graft with one or more plasticizers to produce a plasticized bone graft.  
     
     
         9 . The method of  claim 8 , said step of impregnating, comprising: incubating said cleaned bone graft with a plasticizer composition comprising one or more plasticizers and one or more biocompatible solvents.  
     
     
         10 . The method of  claim 9 , wherein said one or more biocompatible solvents comprise one or more alcohols.  
     
     
         11 . The method of  claim 9 , wherein incubating comprises soaking said cleaned bone graft in said plasticizer composition.  
     
     
         12 . The method of  claim 11 , wherein said soaking is carried out under negative pressure.  
     
     
         13 . The method of  claim 8 , wherein said cleaned bone graft is essentially free from bone marrow elements.  
     
     
         14 . The method of  claim 10 , wherein said one or more plasticizers are present in said plasticizer composition in a weight ratio of from 30 to 90 wt %, and said one or more alcohols are present in said plasticizer composition in a weight ratio of from 10 to 70 wt %.  
     
     
         15 . The method of  claim 14 , wherein said plasticizer is glycerol and said alcohol is isopropyl alcohol.  
     
     
         16 . The method of  claim 15 , wherein said glycerol is present at 30 wt % and said isopropyl alcohol is present at 70 wt %.  
     
     
         17 . A plasticized soft tissue graft suitable for transplantation into a human, comprising: a cleaned soft tissue graft having an internal matrix; and one or more plasticizers contained in said internal matrix.  
     
     
         18 . A plasticized soft tissue graft, comprising: a cleaned, soft tissue graft; and one or more plasticizers, wherein said cleaned soft tissue graft is impregnated with said one or more plasticizers.  
     
     
         19 . A plasticized soft tissue graft, comprising: a cleaned, soft tissue graft comprising one or more plasticizers.  
     
     
         20 . The soft tissue graft of any one of claims  17 ,  18 , or  19 , wherein said soft tissue graft is suitable for direct transplant into a human without rehydration.  
     
     
         21 . The soft tissue graft of any one of claims  17 ,  18 , or  19 , wherein said soft tissue graft is a load-bearing soft tissue graft.  
     
     
         22 . The soft tissue graft of any one of claims  17 ,  18 , or  19 , wherein said soft tissue graft is a non load-bearing soft tissue graft.  
     
     
         23 . The soft tissue graft of any one of claims  17 ,  18 , or  19 , wherein said soft tissue graft is selected from the group consisting of: dura, pericardium, fascia lata, tendons and ligaments.  
     
     
         24 . A method for producing a plasticized soft tissue graft suitable for transplantation into a human, comprising: impregnating a cleaned, soft tissue graft with one or more plasticizers to produce a plasticized soft tissue graft.  
     
     
         25 . The method of  claim 24 , said step of impregnating, comprising: incubating said cleaned, soft tissue graft with a plasticizer composition comprising one or more plasticizers and one or more biocompatible solvents.  
     
     
         26 . The method of  claim 25 , wherein incubating comprises soaking said cleaned, soft tissue graft in said plasticizer composition.  
     
     
         27 . The method of  claim 25 , wherein said soaking is carried out under negative pressure.  
     
     
         28 . The method of  claim 26 , wherein said one or more biocompatible solvents comprise one or more alcohols.  
     
     
         29 . The method of  claim 28 , wherein said one or more plasticizers are present in said plasticizer composition in a weight ratio of from 30 to 90 wt %, and said one or more alcohols are present in said plasticizer composition in a weight ratio of from 10 to 70 wt %.  
     
     
         30 . The method of  claim 28 , wherein said plasticizer is glycerol and said alcohol is isopropyl alcohol.  
     
     
         31 . The method of  claim 30 , wherein said glycerol is present at 30 wt % and said isopropyl alcohol is present at 70 wt %.  
     
     
         32 . A plasticized bone graft, comprising: a cleaned, non-demineralized bone graft comprising one or more plasticizers.  
     
     
         33 . The plasticized bone graft of  claim 32 , wherein the non-demineralized bone graft is non load-bearing.  
     
     
         34 . A plasticized load-bearing, bone graft, comprising: a cleaned, load-bearing bone graft comprising one or more plasticizers.  
     
     
         35 . A plasticized load-bearing soft tissue graft, comprising: a cleaned, load-bearing soft tissue graft comprising one or more plasticizers.  
     
     
         36 . A plasticized bone graft, comprising: a non load-bearing bone graft comprising one or more plasticizers.  
     
     
         37 . A plasticized bone graft, comprising: a non-load-bearing bone graft; and one or more plasticizers, wherein said bone graft is impregnated with said one or more plasticizers.  
     
     
         38 . A method for producing a plasticized bone graft suitable for transplantation into a human, comprising: impregnating a non load-bearing bone graft with one or more plasticizers to produce a plasticized bone graft.  
     
     
         39 . A plasticized soft tissue graft suitable for transplantation into a human, comprising: a soft tissue graft having an internal matrix; and one or more plasticizers contained in said internal matrix.  
     
     
         40 . A plasticized soft tissue graft, comprising: a cleaned soft tissue graft; and one or more plasticizers, wherein said cleaned soft tissue graft is impregnated with said one or more plasticizers.  
     
     
         41 . A plasticized soft tissue graft, comprising: a soft tissue graft comprising one or more plasticizers.  
     
     
         42 . The plasticized soft tissue graft of any one of claims  39 ,  40 , or  41 , wherein said soft tissue graft is a non load-bearing soft tissue graft.  
     
     
         43 . The plasticized soft tissue graft of any one of claims  39 ,  40 , or  41 , wherein said soft tissue graft is a load-bearing soft tissue graft.