Porous orthapedic materials coated with demineralized bone matrix

Abstract

A biomaterial comprising a porous biocompatible structure and a demineralized bone extract coated onto into the pores of the biocompatible structure are provided. The biomaterial may also comprise a demineralized bone gelatin where the gelatin may be coated over the extract coating or mixed with the extract coating before being applied to the biocompatible structure. Methods for making the biomaterial are also provided.

1 . A biomaterial comprising:
 a porous biocompatible structure comprising interconnected pores, wherein the pores comprise interior walls and are interconnected by passageways;   an aqueous demineralized bone extract coating comprising growth factors, proteins or a combination thereof;   a demineralized bone gelatin coating comprising a demineralized bone matrix gelatin; and   wherein the demineralized bone extract coating and the demineralized bone gelatin coating cover the interior walls and passageways.   
     
     
         2 . The biomaterial of  claim 1  wherein the demineralized bone extract coating and the demineralized bone gelatin matrix coating are combined into a single coating material which covers the interior walls and passageways. 
     
     
         3 . The biomaterial of  claim 1  wherein the demineralized bone extract coating covers the interior walls and passageways and the demineralized bone gelatin coating covers the demineralized bone extract coating. 
     
     
         4 . The biomaterial of  claim 1  wherein the demineralized bone extract coating and the demineralized bone gelatin coating are dried on interior walls and passageways. 
     
     
         5 . The biomaterial of  claim 1  wherein the demineralized bone extract coating is an acid soluble demineralized bone coating. 
     
     
         6 . The biomaterial of  claim 1  wherein the demineralized bone extract coating is a guanidine hydrochloride extract. 
     
     
         7 . The biomaterial of  claim 1  wherein the porous biocompatible structure comprises a porous metal, hydroxyapatite or xenograft demineralized cancellous bone. 
     
     
         8 . The biomaterial of  claim 7  wherein the metal is stainless steel, titanium, a titanium alloy, tantalum or a cobalt-chromium alloy. 
     
     
         9 . The biomaterial of  claim 7  wherein the hydroxyapatite comprises tricalcium phosphate. 
     
     
         10 . The biomaterial of  claim 7  wherein the hydroxyapatite comprises a coralline hydroxyapatite. 
     
     
         11 . The biomaterial of  claim 1  wherein the pores have a size of from about 5 microns to about 1000 microns. 
     
     
         12 . The biomaterial of  claim 1  wherein the pores have an average diameter of from about 200 microns to about 500 microns. 
     
     
         13 . The biomaterial of  claim 1  wherein the biomaterial has a form of granules, blocks, cylinders or pre-formed shapes such as hip or knee augments, hip or knee implants, or other orthopedic devices. 
     
     
         14 . The biomaterial of  claim 1  wherein the biomaterial is used as an orthopedic implant. 
     
     
         15 . A biomaterial comprising:
 a porous biocompatible structure comprising interconnected pores, wherein the pores comprise interior walls and are interconnected by passageways; and   an aqueous demineralized bone extract coating comprising growth factors, proteins or a combination thereof, wherein the demineralized bone extract coating covers the interior walls and passageways.   
     
     
         16 . The biomaterial of  claim 15  wherein the demineralized bone extract coating is an acid soluble demineralized bone extract coating. 
     
     
         17 . The biomaterial of  claim 15  wherein the demineralized bone extract coating is a guanidine hydrochloride demineralized bone extract coating. 
     
     
         18 . The biomaterial of  claim 15  wherein the demineralized bone extract coating comprises a growth factor. 
     
     
         19 . The biomaterial of  claim 18  wherein the growth factor is a bone morphogenic protein, TGF-β, IGF-1, VEGF, PDGF, FGF, EGF or mixtures thereof. 
     
     
         20 . The biomaterial of  claim 15  wherein the porous biocompatible structure is metal, wherein the metal is stainless steel, titanium, a titanium alloy, tantalum or a cobalt-chromium alloy. 
     
     
         21 . The biomaterial of  claim 15  wherein the porous biocompatible structure is xenograft demineralized cancellous bone. 
     
     
         22 . The biomaterial of  claim 15  wherein the porous biocompatible structure is hydroxyapatite, the hydroxyapatite comprising tricalcium phosphate or a coralline hydroxyapatite. 
     
     
         23 . The biomaterial of  claim 15  wherein the pores have an average diameter of from about 200 microns to about 500 microns. 
     
     
         24 . The biomaterial of  claim 15  further comprising a demineralized bone gelatin coating. 
     
     
         25 . The biomaterial of  claim 24  wherein the demineralized bone gelatin coating and the demineralized bone extract are combined into a single coating material which covers the interior walls and passageways. 
     
     
         26 . The biomaterial of  claim 24  wherein the demineralized bone extract coating covers the interior walls and passageways and the demineralized bone gelatin coating covers the acid soluble demineralized bone coating. 
     
     
         27 . The biomaterial of  claim 15  wherein the biomaterial has a form of granules, blocks, cylinders or pre-formed shapes such as hip or knee augments, hip or knee implants, or other orthopedic devices 
     
     
         28 . An orthopedic implant comprising:
 a porous biocompatible structure comprising interconnected pores, wherein the pores comprise interior walls and are interconnected by passageways and wherein the pores have an average diameter of from about 200 microns to about 500 microns; and   an aqueous demineralized bone extract coating comprising growth factors, proteins or a combination thereof, wherein the demineralized bone extract coating covers the interior walls and passageways, wherein the bone extract coating is dried on the interior walls and passageways.   
     
     
         29 . The orthopedic implant of  claim 28  wherein the porous biocompatible structure is coralline hydroxyapatite. 
     
     
         30 . The orthopedic implant of  claim 28  wherein the demineralized bone extract is an acid soluble extract. 
     
     
         31 . The orthopedic implant of  claim 28  wherein the demineralized bone extract is a guanidine hydrochloride extract. 
     
     
         32 . The biomaterial of  claim 28  further comprising a demineralized bone gelatin coating, wherein the demineralized bone gelatin coating and the demineralized bone extract are combined into a single coating material which covers the interior walls and passageways. 
     
     
         33 . The biomaterial of  claim 28  further comprising a demineralized bone gelatin coating, wherein the demineralized bone extract coating covers the interior walls and passageways and the demineralized bone gelatin coating covers the acid soluble demineralized bone coating. 
     
     
         34 . A method of preparing a biomaterial comprising:
 a. mixing demineralized bone with an aqueous solution, the aqueous solution comprising a weak acid or guanidine hydrochloride, and wherein the mixing proceeds with constant agitation at a temperature of no greater than 50° C. for a time period of from about 8 hours to about 96 hours to prepare a demineralized bone extract;   b. separating the demineralized bone extract from any remaining solids;   c. diluting, removing or neutralizing the weak acid or guanidine hydrochloride in the demineralized bone extract;   d. coating a porous biocompatible structure with the demineralized bone extract, wherein the porous biocompatible structure has a porosity comprising interconnected pores, the pores comprising interior walls and interconnected by passageways, and wherein the demineralized bone extract infiltrates the pores and coats the interior walls and passageways; and   e. drying the applied demineralized bone extract onto the porous biocompatible structure.   
     
     
         35 . The method of  claim 34  wherein the aqueous solution comprises a weak acid, wherein the weak acid is citric acid, lactic acid, malic acid, acetic acid or a combination thereof. 
     
     
         36 . The method of  claim 34  wherein the aqueous solution comprises a weak acid, the weak acid having a concentration of from about 2 M to about 3 M. 
     
     
         37 . The method of  claim 34  wherein the weak acid or the guanidine hydrochloride is neutralized by adjusting the pH to from about 6.5 to about 7.5 by titrating with a counterion. 
     
     
         38 . The method of  claim 34  wherein the aqueous solution comprises guanidine hydrochloride, the guanidine hydrochloride having a concentration of from about 3 M to about 6 M. 
     
     
         39 . The method of  claim 34  wherein the weak acid or the guanidine hydrochloride is removed from the demineralized bone extract by dialysis, ultrafiltration, hollow fiber filtration or crossflow filtration. 
     
     
         40 . The method of  claim 34  wherein an amount of demineralized bone mixed with the aqueous solution is from about 4 grams to about 7 grams of demineralized bone per about 100 grams of aqueous solution. 
     
     
         42 . The method of  claim 34  wherein the mixing proceeds for a time period of from about 24 hrs to about 96 hrs. 
     
     
         43 . The method of  claim 34  wherein the demineralized bone extract infiltrates the pores under vacuum. 
     
     
         44 . The method of  claim 34  wherein the demineralized bone extract infiltrates the pores by capillary action. 
     
     
         45 . The method of  claim 34  wherein the porous biocompatible material comprises a metal, hydroxyapatite or xenograft demineralized cancellous bone. 
     
     
         46 . The method of  claim 45  wherein the metal is stainless steel, titanium, a titanium alloy, tantalum or a cobalt-chromium alloy. 
     
     
         47 . The method of  claim 45  wherein the hydroxyapatite is a coralline hydroxyapatite. 
     
     
         48 . The method of  claim 34  wherein the pores have an average diameter of from about 200 microns to about 500 microns. 
     
     
         49 . The method of  claim 34  wherein the demineralized bone extract is mixed with a collagen gel before coating the porous biocompatible material and wherein the porous biocompatible material is coated with the combined demineralized bone extract and collagen gel. 
     
     
         50 . The method of  claim 34  further comprising:
 f. mixing the solids separated out in step b with an aqueous saline solution to form a suspension;   g. heating the suspension to a temperature of from about 85° C. to about 130° C. at a pressure of at least 15 psig, dissolving the demineralized bone to produce a demineralized bone gelatin; and   h. mixing the demineralized bone gelatin with the demineralized bone extract before coating the biocompatible structure.   
     
     
         51 . The method of  claim 34  further comprising the steps of:
 f. mixing the solids separated out in step b with an aqueous saline solution to form a suspension;   g. heating the suspension to a temperature of from about 85° C. to about 130° C. at a pressure of at least 15 psig, dissolving the demineralized bone to produce a demineralized bone gelatin solution;   h. applying the demineralized bone gelatin solution over the dried demineralized bone extract on the biocompatible structure, wherein the demineralized bone gelatin solution infiltrates the pores and coats the interior walls and passageways;   i. allowing the applied demineralized bone gelatin solution to gel; and   j. lyophilizing the biocompatible structure and the applied demineralized bone gelatin solution.