Comparative analysis of carrier systems for delivering bone morphogenetic proteins

PURPOSE: The objective of this study was to comparatively assess the bone regenerative capacity of absorbable collagen sponge (ACS), biphasic calcium phosphate block (BCP) and collagenated biphasic calcium phosphate (CBCP) loaded with a low dose of recombinant human bone morphogenetic protein-2 (rhBMP-2). METHODS: The CBCP was characterized by X-ray diffraction and scanning electron microscopy. In rabbit calvaria, four circular 8-mm-diameter defects were created and assigned to one of four groups: (1) blood-filled group (control), (2) rhBMP-2-soaked absorbable collagen sponge (0.05 mg/mL, 0.1 mL; CS group), (3) rhBMP-2-loaded BCP (BCP group), or (4) rhBMP-2-loaded CBCP (CBCP group). The animals were sacrificed either 2 weeks or 8 weeks postoperatively. Histological and histomorphometric analyses were performed. RESULTS: The CBCP showed web-like collagen fibrils on and between particles. Greater dimensional stability was observed in the BCP and CBCP groups than in the control and the CS groups at 2 and 8 weeks. The new bone formation was significantly greater in the BCP and CBCP groups than in the control and CS groups at 2 weeks, but did not significantly differ among the four groups at 8 week. The CBCP group exhibited more new bone formation in the intergranular space and in the center of the defect compared to the BCP group at 2 weeks, but a similar histologic appearance was observed in both groups at 8 weeks. CONCLUSIONS: The dose of rhBMP-2 in the present study enhanced bone regeneration in the early healing period when loaded on BCP and CBCP in rabbit calvarial defects. GRAPHICAL ABSTRACT: [Image: see text]