Biocompatible bone implant compositions and methods for repairing a bone defect

Abstract

Moldable bone implants for use in a bone defect or wound include a plurality of biocompatible granules and a biocompatible polymer that together form an implant mass. The polymer is softened with a plasticizer to make the implant mass moldable or flowable. The plasticizer can dissipate or be extracted to cause the implant mass to harden. The implant mass can be shaped in-situ or ex-situ. Implants formed in-situ are shaped by the bone defect or wound. The implant becomes hard through contact with body fluids, which extracts the plasticizer from the implant mass. Bone implants formed ex-situ, such as in a mold, are shaped by a mold, for example, and then hardened by placing the implant mass in contact with a hardening agent, such as water, which extracts the plasticizer from the implant mass. The shaped, hardened implant can be placed into a bone defect of corresponding size and shape.

1 . An implant composition for use in repairing a bone defect in a living organism, comprising: 
 a plurality of biocompatible granules;    a biocompatible polymer on at least a portion of the biocompatible granules so as to form an implant mass comprising the biocompatible granules and the biocompatible polymer; and    a plasticizer in the implant mass in an amount sufficient to condition at least a portion of the biocompatible polymer so that the implant mass is initially flowable and then hardenable upon removal of at least a portion of the plasticizer from the implant mass.    
   
   
       2 . An implant composition as defined in  claim 1 , wherein the biocompatible granules comprise a material selected from the group consisting of biocompatible ceramics, biocompatible glasses, biocompatible polymers, and combinations thereof.  
   
   
       3 . An implant composition as defined in  claim 1 , wherein the biocompatible granules comprise a material selected from the group consisting of silicon oxide, calcium sulfate, calcium phosphate, and combinations thereof.  
   
   
       4 . An implant composition as defined in  claim 1 , wherein the biocompatible granules comprise a material selected from the group consisting of monocalcium phosphate monohydrate, monocalcium phosphate anhydrous, dicalcium phosphate dihydrate, dicalcium phosphate anhydrous, tetracalcium phosphate, calcium orthophosphate phosphate, calcium pyrophosphate, α-tricalcium phosphate, β-tricalcium phosphate, hydroxyapatite, carbonate hydroxyapatite, apatite, bioglass, and combinations thereof.  
   
   
       5 . An implant composition as defined in  claim 1 , wherein the biocompatible granules are biodegradable.  
   
   
       6 . An implant composition as in defined  claim 1 , wherein the biocompatible polymer is biodegradable.  
   
   
       7 . An implant composition as defined in  claim 1 , wherein the biocompatible polymer is selected from the group consisting of poly(α-hydroxyesters), poly(orthoesters), poly(ether esters), polyanhydrides, poly(phosphazenes), poly(propylene fumarates), poly(ester amides), poly(ethylene fumarates), poly(amino acids), polysaccharides, polypeptides, poly(hydroxy butyrates), poly(hydroxy valerates), polyurethanes, poly(malic acid), polylactides, polyglycolides, poly(lactide-co-glycolide), polycaprolactones, poly(glycolide-co-trimethylene carbonates), polydioxanones, and co-polymers, terpolymers thereof and blends of those polymers.  
   
   
       8 . An implant composition as defined in  claim 1 , wherein the biocompatible polymer comprises poly(lactide-co-glycolide).  
   
   
       9 . An implant composition as in  claim 1 , wherein the plasticizer is selected from the group consisting of n-methyl-2-pyrrolidone, acetone, ethyl lactate, ethyl acetate, ethyl formiate, acetyltributylcitrate, triethyl citrate, lactic acid, citric acid tetrahydrofuran, toluene, alcohol, and carbon dioxide.  
   
   
       10 . An implant composition as in defined  claim 1 , further comprising a biologically active substance.  
   
   
       11 . An implant composition as defined in  claim 1 , wherein the implant composition is pre-packaged within a syringe capable of injecting the implant composition into a bone defect.  
   
   
       12 . An implant composition as defined in  claim 1 , wherein said plasticizer comprises a liquid solvent that is added in sufficient quantities to liquefy at least a portion of the biocompatible polymer.  
   
   
       13 . An implant composition as in  claim 12 , wherein said plasticizer is extractable from the implant mass when contacted with a hardener.  
   
   
       14 . An implant composition as defined in  claim 13 , wherein the hardener comprises water or a body fluid.  
   
   
       15 . A method for repairing a defect or wound in a bone of a living organism, comprising: 
 providing an implant mass comprising a plurality of biocompatible granules, said biocompatible comprising one or more biocompatible polymers;    exposing the implant mass to a plasticizer to condition the biocompatible polymer to yield a flowable implant mass; and    shaping the implant mass into a desired shape for repairing a bone defect in a living organism.    
   
   
       16 . A method as defined in  claim 15 , wherein exposing the implant mass to a plasticizer comprises immersing the implant mass in a liquid plasticizer.  
   
   
       17 . A method as defined in  claim 15 , wherein exposing the implant mass to a plasticizer comprises immersing the implant mass in a gaseous plasticizer.  
   
   
       18 . A method as defined in  claim 15 , wherein the implant mass is pre-packaged within a syringe and shaping the moldable implant mass comprises injecting the implant mass into a bone defect using the syringe.  
   
   
       19 . A method as defined in  claim 18 , wherein the implant mass hardens as a result of the plasticizer being extracted from the implant mass by body fluid in contact therewith.  
   
   
       20 . A method as defined in  claim 15 , wherein shaping the implant mass comprises: 
 placing the implant mass into a mold having a mold cavity corresponding to a shape of a bone defect in order for the implant mass to be formed into the shape of the bone defect;    applying a hardening substance to the shaped implant mass to cause the shaped implant mass to harden; and    removing the hardened implant mass from the mold and inserting the solidified implant mass into a bone defect in a living organism.    
   
   
       21 . A method as defined in claim.  20 , wherein the hardening substance comprises water that causes hardening by extracting the plasticizer from the implant mass.  
   
   
       22 . A method as defined in  claim 15 , said biocompatible granules further comprising biocompatible particles coated by said one or more biocompatible polymers.  
   
   
       23 . A method for repairing a defect or wound in a bone of a living organism, comprising: 
 placing an implant mass into a bone defect or void, the implant mass comprising a plurality of biocompatible granules, at least a portion of which comprise a biocompatible polymer;    while the granules are in the bone defect or void, exposing the implant mass to a plasticizer to condition the biocompatible polymer;: and allowing a body fluid in contact with the implant mass to extract the plasticizer therefrom in order to cause the implant mass to harden, wherein the plurality of granules in the hardened implant mass adhere to one another.