Animals ; Bone Morphogenetic Protein 2/pharmacology* ; Bone Regeneration/drug effects* ; Bone Substitutes/pharmacology* ; Calcium Phosphates/pharmacology* ; Collagen/pharmacology ; Drug Carriers ; Models, Animal ; Rabbits ; Recombinant Proteins/pharmacology ; Skull/surgery* ; Transforming Growth Factor beta/pharmacology*
Keywords
biphasic calcium phosphate ; bone morphogenetic protein 2 ; bone regeneration ; bone substitutes ; collagen
Abstract
OBJECTIVES: This study compared the bone regenerative effects of a recombinant human bone morphogenetic protein 2 (rhBMP-2)-loaded collagen-based biphasic calcium phosphate composite (BCPC) and rhBMP-2-loaded biphasic calcium phosphate (BCP).
MATERIAL AND METHODS: The in vitro release profiles of rhBMP-2-loaded BCP and BCPC were measured. The animal surgery was performed on ten rabbits. Four 8-mm-diameter circular calvarial defects were made and filled with BCP, BCPC, rhBMP-2-loaded BCP (BMP + BCP) and rhBMP-2-loaded BCPC (BMP + BCPC). The animals were euthanized either 2 or 8 weeks after surgery.
RESULTS: The initial burst release of rhBMP-2 was greater for BCP than for BCPC, and both presented a slow release pattern thereafter. In rabbit calvarial defects, the space maintaining capability and graft resorption of all experimental groups did not show statistical differences at 2 and 8 weeks. New bone formation in the rhBMP-2-loaded groups was greater than in the non-loaded groups at both weeks, but the amount of new bone was comparable between both rhBMP-2-loaded groups at both weeks. There was a distinct histologic difference between the BMP + BCP and BMP + BCPC groups at 2 weeks; the new bone formation occurred more in the intergranular spaces and the BCP-to-bone contact was greater in the BMP + BCPC group, but these differences were no longer discernible at 8 weeks.
CONCLUSIONS: BCP- and BCPC-loaded rhBMP-2 significantly improved bone regeneration and BCPC led to a dense network of new bone and bone particles during the early healing period. BCPC can therefore be considered as a promising candidate for carrying rhBMP-2.