Porous polymer scaffold and methods thereof

Abstract

The present invention relates to a method of treating a bone defect site in a patient. The method includes applying to the bone defect site a bone graft composition comprising a scaffold having a desired shape. The scaffold includes a biodegradable polymer and a ceramic material. The scaffold includes interconnected pores and an average porosity range of about 50% to about 90%, wherein the porosity is substantially uniform throughout the scaffold. The scaffold is bioresorbable and exhibits advantageous mechanical properties that mimic those found in natural bone. Methods of preparing the scaffolds and using them in skeletal tissue engineering applications (e.g., as bone grafts to repair osteochondral defects and ligaments) is also described.

What is claimed is: 
     
         1 . A method of treating a bone defect site in a patient in need thereof, the method comprising:
 applying to the bone defect site a bone graft composition comprising a scaffold having a desired shape, the scaffold comprising:
 a biodegradable polymer, and 
 a ceramic material, 
 wherein the scaffold comprises interconnected pores and an average porosity range of about 50% to about 90%, wherein the porosity is substantially uniform throughout the scaffold. 
   
     
     
         2 . The method of  claim 1 , wherein applying to the bone defect site the bone graft composition comprises surgically implanting the bone graft composition. 
     
     
         3 . The method of  claim 1 , wherein the biodegradable polymer is selected from the group consisting of: polycaprolactone, poly(lactic-co-glycolic acid), poly(lactic acid), polyhydroxybutyrate, poly(lactide-co-caprolactone), and poly(3-hydroxybutyrate-co-3-hydroxyvalerate). 
     
     
         4 . The method of  claim 1 , wherein the ceramic material is selected from the group consisting of: tricalcium phosphate, hydroxyapatite, biphasic calcium phosphate, and bioglass. 
     
     
         5 . The method of  claim 1 , wherein the average porosity is in the range of about 60% to about 80%. 
     
     
         6 . The method of  claim 1 , wherein the pores of the scaffold have an average pore size of about 450 μm to about 600 μm. 
     
     
         7 . The method of  claim 1 , wherein the desired shape is an anatomical shape. 
     
     
         8 . The method of  claim 1 , wherein the desired shape is in the form of a biological tissue. 
     
     
         9 . The method of  claim 1 , wherein the desired shape is in the form of a bone graft. 
     
     
         10 . The method of  claim 9 , wherein the bone graft composition comprises a bioactive agent. 
     
     
         11 . The method of  claim 10 , wherein the bioactive agent is selected from the group consisting of: stem cells, bone marrow, plasma, growth factors, antibiotics, and immunosuppressive agents, or combinations thereof. 
     
     
         12 . The method of  claim 10 , wherein the bioactive agent comprises stem cells, the method further comprising harvesting the stem cells from the patient. 
     
     
         13 . The method of  claim 12  wherein the stem cells are adipose derived stem cells. 
     
     
         14 . The method of  claim 12 , wherein the bioactive agent comprises differentiated mesenchymal stem cells harvested from the patient. 
     
     
         15 . The method of  claim 12 , wherein the scaffold is a suitable platform for stem cell differentiation. 
     
     
         16 . The method of  claim 10 , wherein the bioactive agent comprises differentiated mesenchymal stem cells, the method further comprising harvesting the stem cells from a donor. 
     
     
         17 . The method of  claim 1 , wherein the scaffold is prepared by a process comprising:
 heating a mixture comprising the biodegradable polymer, the ceramic material, and a porogen;   compressing the heated mixture at a pressure of about 5 MPa to about 110 MPa;   cooling the compression to form a bulk substrate;   selectively removing a material from the bulk substrate to afford a shaped substrate; and   removing the porogen from the shaped substrate to afford the scaffold having a desired shape.   
     
     
         18 . The method of  claim 17 , wherein the scaffold comprises at least about 50% by volume of the ceramic material. 
     
     
         19 . The method of  claim 17 , wherein selectively removing material from the bulk substrate comprises excising at least some of the bulk substrate by way of milling, lathing, drilling or cutting the bulk substrate to afford a desired shape. 
     
     
         20 . The method of  claim 17 , wherein the porogen comprises sodium chloride or poly(methyl methacrylate).