Plga/hydroxyapatite composite bone grafts and method of making

Abstract

The present invention involves tissue engineering constructs made from a new composite bone graft material made from biocompatible poly(D,L-lactic-co-glycolic acid) (PLGA) and bioceramic particles exposed on its surface using a gas foaming particle leaching (GF/PL) method and infused with collagen. Methods and apparatus for of forming scaffolds are also disclosed.

1 - 56 . (canceled) 
     
     
         57 . A bone graft biomaterial comprised of a scaffold consisting of a biocompatible polymer and a bioceramic composite in a ratio of about 1:2 to about 2:1 wherein the bioceramic particles are less than 1000 nm in diameter and wherein the scaffolds contain interconnected pores made via a gas foaming or a particulate leaching process, wherein the bioceramic particles are exposed on the surface of the biomaterial and wherein the biomaterial is impregnated with collagen after the pores are formed by forcing the collagen into the pores by placing the scaffold into a collagen solution and the solution is placed under a vacuum until the temperature is just above the freezing point of the collagen solution, the solution allowed to warm before being subjected to repeated cycles of vacuum and warming. 
     
     
         58 . The bone graft material of  claim 57  wherein the biocompatible polymer is selected from the group comprising Poly lactic acid (PLA), poly glycolic acid (PGA), Poly lactic co-glycolic acid (PLGA), and copolymers with polyethylene glycol (PEG); polyanhydrides, poly(ortho)esters, polyurethanes, poly(butyric acid), poly(valeric acid), poly(lactide-co-caprolactone) and trimethylene carbonate and combinations and co-polymers thereof. 
     
     
         59 . The bone graft material of claim of  claim 57  wherein the bioceramic is selected from the group consisting of hydroxyapatite, tricalcium phosphate, bioglass, calcium phosphate or bone or a combination thereof. 
     
     
         60 . The bone graft material of  claim 57  wherein the bioceramic particles are from 100 nm to 1000 nm in diameter. 
     
     
         61 . The bone graft material of  claim 60  wherein the bioceramic particles are from 100 nm to 400 nm in diameter. 
     
     
         62 . The bone graft material of  claim 57  wherein the biocompatible polymer is poly lactic acid, poly glycolic acid, lactide or caprolactone or copolymers or combinations thereof. 
     
     
         63 . The bone graft material of  claim 62  comprising two polymers in a ratio from 2:1 to 1:2. 
     
     
         64 . The bone graft material of  claim 62  where the polymers are lactide and caprolactone in a ratio of about 75:25 by weight. 
     
     
         65 . A bone graft biomaterial of  claim 57  wherein the bioceramic is TCP coated hydroxyapatite. 
     
     
         66 . The bone graft material of  claim 57  wherein the ratio of biocompatible polymer to bioceramic ranges from about 80:20 to about 50:50. 
     
     
         67 . The bone graft material of  claim 64  wherein the ratio of polymer to bioceramic is about 60:40 
     
     
         68 . The bone graft material of  claim 59  where in the bioceramic particles are a mixture of hydroxy apatite and TCP in a ratio of about 40:60. 
     
     
         69 . A bone graft material comprising lactide and caprolactone polymers in a ratio from about 1:2 to about 2:1 which are in a ratio of from about 80:20 to about 50:50 with a bioceramic having a diameter from about 150 microns to about 300 microns comprising hydroxyapatite, TCP, hydroxyapatite TCP or a mixture thereof wherein the scaffold is formed via gas foaming. 
     
     
         70 . The bone graft material of  claim 69  where in the ratio of lactide to caprolactone is 75:25. 
     
     
         71 . The bone graft material of  claim 69  wherein the ratio of lactide and caprolactone polymers to bioceramic is about 60:40. 
     
     
         72 . The bone graft material of  claim 57  wherein the material is compressed using an inert gas at pressures from about 400 psi to about 3000 psi for a period of about 1 to about 8 hours, before reducing pressure to ambient with a period of about 10 minutes to about 30 minutes. 
     
     
         73 . The bone graft material of  claim 72  wherein the material is compressed using an inert gas at pressures from about 1500 to about 2500 PSI for a period of about 1-5 hours before reducing pressure to ambient with a period of about 10 minutes to about 30 minutes. 
     
     
         74 . A method of fabricating a polymer and hydroxyapatite biomaterial scaffold for use in replacing bone comprising:
 a) introducing a biocompatible polymer selected from selected from the group comprising Poly lactic acid (PLA), poly glycolic acid (PGA), Poly lactic co-glycolic acid (PLGA), and copolymers with polyethylene glycol (PEG); polyanhydrides, poly(ortho)esters, polyurethanes, poly(butyric acid), poly(valeric acid), poly(lactide-co-caprolactone) and trimethylene carbonate and combinations and co-polymers thereof and a bioceramic selected from of hydroxyapatite, tricalcium phosphate, bioglass, calcium phosphate or bone or a combination thereof into a mold in a pressure reactor;   b) pressurizing the reactor with an inert gas to form a scaffold;   c) reducing the pressures to induce pore forming bubbles in the scaffold; and   d) introducing the scaffold to a collagen solution;   e) driving the collagen solution into the scaffold using pressure or a vacuum; and   f) optionally shaping the scaffold using cutting tools.   
     
     
         75 . The method of  claim 74  wherein the mold further comprises a Teflon sheath. 
     
     
         76 . The method of  claim 75  wherein the scaffold is shaped with a water jet. 
     
     
         77 . The method of  claim 74  having the following steps prior to step a:
 i) imaging a region in a patient requiring bone replacement to obtain the dimensions of bone requiring replacement 
 ii) using the dimensions of the bone requiring replacement to determine the dimensions of the required bone graft 
 iii) fabricating a mold for a pressure reactor using the calculated bone replacement dimensions.