Enhanced bone augmentation by controlled release of recombinant human bone morphogenetic protein-2 from bioabsorbable membranes

Abstract

Background: The present study was undertaken to determine the effect of recombinant human bone morphogenetic protein-2 (rhBMP-2)-loaded biodegradable membranes on bone augmentation in a rabbit calvarial model. Methods: Five μg of rhBMP-2 was loaded into a stiff hemispherical dome membrane made of poly(L-lactide) and tricalcium phosphate (PLLA/TCP). The release kinetics of rhBMP-2 from the membrane were determined in vitro using a human BMP-2 immunoassay. Twelve rhBMP-2-loaded dome membranes (test group) and 12 control dome membranes (control group) were placed on the partial-thickness calvarial defects of 24 rabbits. The animals were sacrificed at 4 and 8 weeks, and undecalcified ground sections were prepared. Newly formed bone area and height were measured histomorphometrically and calculated by percentage ratio to the total submembranous space area and height below the dome. Results: In vitro release results demonstrated that rhBMP-2 was released consistently over a 4-week period following a high initial burst release on the first day. At both 4 and 8 weeks, histomorphometric analysis revealed that the test group showed significantly higher newly formed bone heights and areas than the control group (P <0.01). In the control group, new bone height was 36.3% of the dome height and the new bone area reached 8.2% of the submembranous space area at 8 weeks, while the test group reached 87.3% and 35.4%, respectively. Conclusion: These results suggest that the use of rhBMP-2-loaded PLLA/TCP membranes can result in additional bone augmentation, which is due to the osteoinductive properties of rhBMP-2 released from the membrane during healing.