Bone graft substitute

Abstract

A bone graft substitute in the form of an implantable three-dimensional scaffold that includes calcium phosphate and has pores. The scaffold is impregnated with a calcium and/or phosphate containing substance, and the dissolution rate DR S of the scaffold is slower than the dissolution rate DR D of the calcium and/or phosphate containing substance.

1 . A bone graft substitute in the form of an implantable three-dimensional scaffold comprising calcium phosphate and having pores, wherein:
 (i) the scaffold is impregnated with a calcium and/or phosphate containing substance;   (ii) the dissolution rate DR S  of said scaffold being slower than the dissolution rate DR D  of said calcium and/or phosphate containing substance used for the impregnation of the scaffold; whereby and   (iii) the chemical composition and integrity of the scaffold remains essentially unaffected by said impregnation with said calcium and/or phosphate containing substance.   
     
     
         2 . The bone graft substitute according to  claim 1 , wherein said calcium and/or phosphate containing substance is ionic. 
     
     
         3 . The bone graft substitute according to  claim 1 , wherein said calcium and/or phosphate containing substance is crystalline. 
     
     
         4 . The bone graft substitute according to  claim 3 , wherein said calcium and/or phosphate containing substance has a degree of crystallinity higher than 80%. 
     
     
         5 . The bone graft substitute according to  claim 1 , wherein said calcium and/or phosphate containing substance is not chemically bound to said scaffold. 
     
     
         6 . The bone graft substitute according to  claim 1 , wherein said calcium and/or phosphate containing substance only adheres physically to said scaffold. 
     
     
         7 . The bone graft substitute according to  claim 1 , wherein said dissolution rate DR D  as measured in a phosphate-buffered solution (PBS) at pH 7.4 is at least 10 times larger than said dissolution rate DR S . 
     
     
         8 . The bone graft substitute according to  claim 1 , wherein said dissolution rate DR D  as measured in an aqueous citric acid solution at pH 3.0 is at least 10 times larger than said dissolution rate DR S . 
     
     
         9 . The bone graft substitute according to  claim 1 , wherein said dissolution rate DR S =0 and said dissolution rate DR D >0 in serum or simulated body fluid having a pH 7.4 at 37° C. and 5% CO 2  in the atmosphere. 
     
     
         10 . The bone graft substitute according to  claim 1 , wherein said calcium and/or phosphate containing substance is rigid. 
     
     
         11 . The bone graft substitute according to  claim 1 , wherein the degree of porosity of said scaffold is 40-95%. 
     
     
         12 . The bone graft substitute according to  claim 1 , wherein said scaffold has micropores with a mean diameter D micro  smaller than 10 microns. 
     
     
         13 . The bone graft substitute according to  claim 1 , wherein said scaffold has macropores with a mean diameter D macro  in the range of 0.03 to 1 mm. 
     
     
         14 . The bone graft substitute according to  claim 1 , wherein said scaffold has a specific surface area superior to 1 m 2 /g. 
     
     
         15 . The bone graft substitute according to  claim 1 , wherein the tortuosity of the pores of said scaffold is larger than 3. 
     
     
         16 . The bone graft substitute according to  claim 1 , wherein said pores are interconnected. 
     
     
         17 . The bone graft substitute according to  claim 13 , wherein the size of interconnections between the pores is larger than 30 microns. 
     
     
         18 . The bone graft substitute according to  claim 1 , wherein said calcium and/or phosphate containing substance comprises calcium chloride. 
     
     
         19 . The bone graft substitute according to  claim 1 , wherein said calcium and/or phosphate containing substance comprises K 2 HPO 4 . 
     
     
         20 . The bone graft substitute according to  claim 1 , wherein the ratio WD/WS between the weight WD of said calcium and/or phosphate containing substance and the weight WS of said scaffold is comprised in the range of 0.1 to 0. 
     
     
         21 . The bone graft substitute according to  claim 1 , wherein said calcium phosphate of said scaffold is beta-tricalcium phosphate (β-TCP). 
     
     
         22 . The bone graft substitute according to  claim 1 , wherein said scaffold has a volume larger than 10 mm 3 . 
     
     
         23 . The bone graft substitute according to  claim 1 , wherein said pores are filled with said calcium and/or phosphate containing substance to an extent of 1% to 50 vol.-%. 
     
     
         24 . A method for manufacturing a bone graft substitute, the method comprising impregnating a three-dimensional scaffold comprising calcium phosphate having interconnected pores with a calcium and/or phosphate containing substance, wherein the chemical composition and integrity of said scaffold remains essentially unaffected by said impregnation with said calcium and/or phosphate containing substance. 
     
     
         25 . The method according to  claim 24 , wherein the calcium and/or phosphate containing substance is calcium chloride and the impregnating is performed by applying an aqueous solution of calcium chloride to said scaffold. 
     
     
         26 . The method according to  claim 24 , wherein the calcium and/or phosphate containing substance is K 2 HPO 4  and the impregnating is performed by applying an aqueous solution of calcium chloride to said scaffold. 
     
     
         27 . The method according to  claim 24 , wherein said aqueous solution applied to said scaffold is dried in an atmosphere having a relative humidity of 0%. 
     
     
         28 . The method according to  claim 24 , wherein said aqueous solution applied to said scaffold is dried for more than 1 day. 
     
     
         29 . The method according to  claim 24 , wherein said aqueous solution has a concentration of 12.5% to 50%. 
     
     
         30 . The method according to  claim 24 , wherein said impregnating is performed in two successive steps. 
     
     
         31 . The method according to  claim 30 , wherein one step of the two successive steps comprises impregnating the scaffold with a calcium-containing substance and another step of the two successive steps comprises impregnating the scaffold with a phosphate-containing substance.