Synthetic biomaterial compound of calcium phosphate phases particularly adapted for supporting bone cell activity

Abstract

The present invention is directed to a synthetic biomaterial compound based on stabilized calcium phosphates and more particularly to the molecular, structural and physical characterization of this compound. The compound comprises calcium, oxygen and phosphorous, wherein at least one of the elements is substituted with an element having an ionic radius of approximately 0.1 to 1.1 Å. The knowledge of the specific molecular and chemical properties of the compound allows for the development of several uses of the compound in various bone-related clinical conditions.

1. An isolated bioresorbable biomaterial compound comprising calcium, oxygen and phosphorous, wherein a portion of at least one of said elements is substituted with an element having an ionic radius of approximately 0.1 to 0.6 Å  Si 4+   , wherein said compound has a microporous structure . 
     
     
       2. The biomaterial compound as claimed in  claim 1 , wherein a portion of the phosphorous is substituted by at least one element having an ionic radius of approximately 0.1 to 0.4 Å. 
     
     
       3. The biomaterial compound as claimed in  claim 2 , further comprising an additional element having an effective charge to compensate any imbalance of charge resulting from the partial substitution of phosphorous. 
     
     
       4. The biomaterial compound as claimed in  claim 1 , wherein said element is silicon. 
     
     
       5. The biomaterial compound as claimed in  claim 1 , wherein said compound has a microporous structure. 
     
     
       6. The biomaterial compound as claimed in claim  5    1  wherein said compound is formed as a macroporous structure comprising an open cell construction with interconnected voids having a pore size of approximately 50 to 1000 microns. 
     
     
       7. The biomaterial compound as claimed in  claim 6  wherein said macroporous structure is formed by coating said compound onto a reticulated polymer and subsequently removing said polymer through pyrolysis. 
     
     
       8. The biomaterial compound as claimed in  claim 5 , wherein said compound has a nanoporous structure. 
     
     
       9. The biomaterial compound as claimed in claims  1 , wherein said compound exhibits monoclinic pseudo-rhombic symmetry and is in the monoclinic space group P2 1 /a. 
     
     
       10. The biomaterial compound as claimed in  claim 1 , wherein said compound is resorbed by the cellular activity of osteoclasts and promotes the generation of new mineralized bone matrix by the activity of osteoblasts. 
     
     
       11. The biomaterial compound as claimed in  claim 10 , wherein said compound is progressively replaced with natural bone in vivo. 
     
     
       12. The biomaterial compound as claimed in  claim 10 , wherein said compound is essentially insoluble in biological media at human physiological pH of 6.4-7.3. 
     
     
       13. A biomaterial compound as claimed in  claim 1 , wherein the calcium to phosphorous atomic ratio is less than 1.67. 
     
     
       14. The biomaterial compound as claimed in  claim 1 , wherein said element is boron. 
     
     
       15. A biomaterial compound comprising calcium, oxygen and phosphorous, wherein at least one of said elements is substituted with an element having an ionic radius of approximately 0.1 to 1.1 Å and wherein said compound is selected from the group consisting of Ca 3 (P 0.750 Si 0.25 O 3.875 ) 2  and Ca 3 (P 0.9375 Si 0.0625 O 3.96875 ) 2 . 
     
     
       16. A biomaterial composition comprising the compound as claimed in  claim 1  and further comprising monoclinic hydroxyapatite. 
     
     
       17. A biomaterial composition comprising the biomaterial compound as claimed in  claim 12  and further comprising collagen. 
     
     
       18. A biomaterial compound having the formula:
   (Ca) i {(P 1-x-y-z B x C y D z )O j } 2    
 wherein B, C and D are selected from those elements having an ionic radius of approximately 0.1 to  0.4 Å and selected from the group consisting of silicon and boron ;  
 x is greater than or equal to zero but less than 1;  
 y is greater than or equal to zero but less than 1;  
 z is greater than or equal to zero but less than 1;  
 x+y+z is greater than zero but less than 1;  
 i is greater than or equal to 2 but less than or equal to 4; and  
 j is equal to 4-δ, where δ is greater than or equal to zero but less than or equal to 1.  
 
     
     
       19. The biomaterial compound as claimed in  claim 18 , wherein δ is determined by charge compensation of the elements present in the compound. 
     
     
       20. The biomaterial compound as claimed in  claim 18 , wherein B is silicon. 
     
     
       21. The biomaterial compound as claimed in  claim 18 , wherein B is boron. 
     
     
       22. A biomaterial composition comprising the biomaterial compound as claimed in  claim 18  and further comprising at least one calcium material selected from the group consisting of calcium hydroxyapatite, α-TCP, β-TCP, octacalcium phosphate, tetracalcium phosphate, dicalcium phosphate and calcium oxide. 
     
     
       23. The biomaterial composition as claimed in  claim 22 , wherein said composition comprises calcium hydroxyapatite and said composition is characterized by those peaks in the x-ray diffraction spectrum of FIG.  9 . 
     
     
       24. The biomaterial composition as claimed in  claim 22 , wherein B is silicon and wherein said compound is mixed with calcium hydroxyapatite in a ratio of approximately 20:80 to 80:20. 
     
     
       25. The biomaterial composition as claimed in  claim 22  wherein said composition additionally comprises an additive to increase the mechanical toughness and strength of said biomaterial composition. 
     
     
       26. The biomaterial composition as claimed in  claim 22 , wherein said composition exists as a physical mixture or a solid solution. 
     
     
       27. A composition as claimed in  claim 22 , wherein the  said composition exists as a fine or coarse powder, pellets, three-dimensional shaped pieces, macroporous structures and  or coatings. 
     
     
       28. A composition as claimed in  claim 22 , wherein said composition is resorbed by the cellular activity of osteoclasts and promotes the generation of new mineralized bone matrix by the activity of osteoblasts.