Artificial stabilized composition of calcium phosphate phases particularly adapted for supporting bone cell activity

Abstract

This invention relates to a bioactive artificial sintered composition for providing a morphology capable of consistently supporting bone cell activity thereon. The composition comprises stabilized calcium phosphate phases developed by the conversion of a hydroxyapatite substance in the presence of stabilizing entities at sintering temperatures into insolubilized and stabilized tricalcium phosphate. The present invention has numerous applications in medical diagnostics for the assessment of abnormal bone cell activity as well as for medical therapeutics, including bone and dental tissue replacement and repair as well as for ex vivo bone graft tissue engineering.

1 . A bioactive artificial sintered composition for supporting bone cell activity, said composition comprising: 
 a powder or bulk material of stabilized insoluble tricalcium phosphate wherein the tricalcium phosphate is stabilized with stabilizing entities uniformly throughout the entire composition, and wherein said uniformly stabilized tricalcium phosphate is resorbable by osteoclasts and promotes secretion of mineralized bone matrix by osteoblasts,    wherein said stabilizing entities are selected from the group consisting of silicon entities, aluminum entities, barium entities, titanium entities, germanium entities, chromium entities, vanadium entities, niobium entities, boron entities and mixtures thereof.    
     
     
         2 . A composition as claimed in  claim 1 , wherein said stabilized tricalcium phosphate is primarily alpha tricalcium phosphate.  
     
     
         3 . A composition as claimed in  claim 1 , wherein said stabilizing entities are provided as a solution.  
     
     
         4 . The composition as claimed in  claim 3 , wherein said stabilizing entities are a solution of tetrapropyl orthosilicate.  
     
     
         5 . A composition as claimed in  claim 1 , wherein said composition is insoluble in physiological fluids of pH of approximately 6.4 to 7.3.  
     
     
         6 . The composition of  claim 1 , where said composition is provided as a microporous polycrystalline structure.  
     
     
         7 . The composition of  claim 6 , wherein said structure has said globular morphology of  FIG. 14 .  
     
     
         8 . The composition of  claim 7 , wherein said morphology comprises rounded granules with a lateral dimension of about 0.5 to 1 μm.  
     
     
         9 . The composition of  claim 6 , wherein said composition has an internal macroporosity.  
     
     
         10 . The composition of  claim 1 , wherein said stabilizing entities are silicon.  
     
     
         11 . An implantable device coated with the composition of  claim 1 .  
     
     
         12 . An implantable device consisting essentially of the composition of  claim 1 .  
     
     
         13 . An implantable calcified bone matrix comprising: 
 a) the composition of  claim 1  forming a structure for supporting said bone matrix; and    b) a calcified bone matrix secreted by osteoblasts on said structure.    
     
     
         14 . An implantable calcified bone matrix of  claim 13 , wherein said matrix is free of bone cells including osteoblasts.  
     
     
         15 . An implantable calcified bone matrix of  claim 13 , wherein said matrix includes a patients bone cells including osteoblasts.  
     
     
         16 . A process for making the composition of  claim 1 , said process comprising: 
 doping and mixing a hydroxyapatite substance with a composition of stabilizing entities to uniformly distribute said stabilizing entities throughout said entire hydroxyapatite substance;    and sintering said uniformly doped hydroxyapatite substance;    wherein sintering converts at least a portion of said uniformly doped hydroxyapatite substance into primarily alpha tricalcium phosphate.    
     
     
         17 . The process of  claim 16 , wherein sintering is done at temperatures of about 900° C. to 1100° C.  
     
     
         18 . A method for the culturing of functional bone cells, said method comprising: 
 applying a suspension of bone cells in physiological media to the composition of  claim 1  provided as a substrate.    
     
     
         19 . A method of the ex vivo engineering of a mineralized collagenous implant, the method comprising the steps of: 
 a) providing the composition of  claim 1  as a bulk material;    b) applying a suspension of osteoblasts on said composition and incubating for a time sufficient for said osteoblasts to secrete mineralized collagenous bone matrix on said bulk material; and    c) implanting the product of step (b) in a patient.