Bone Abstracts

Delivery of recombinant human bone morphogenetic protein (rhBMP2) with various carriers has been showing the successful induction of bone formation in many bony defects, including oral and maxillofacial regions. However, effectiveness of the exogenous proteins, when repeatedly administered into different regions in an individual, has not been determined. The present study was aimed to examine alterations of ectopic or orthotopic bone generation and serum level of anti-BMP2 antibody following the repeated administration of rhBMP2. Absorbable collagen sponge or thermosensitive hydrogel containing rhBMP2 (7 μg) was subcutaneously implanted or injected twice at 4 week intervals into both sides of the back in C57BL/6 mice, respectively. Microradiographic and histological analyses showed that the second administration of rhBMP2 (7 μg) also induced the same amount of heterotopic bone in the subcutaneous regions compared to the first administration, regardless of carrier type. When the same amount of rhBMP2 was primarily delivered with the hydrogel into subcutaneous region of the back and 3 weeks later another rhBMP2 was implanted with absorbable collagen sponge into calvarial defects, the defects were completely recovered with newly regenerated bones at three additional weeks after the second implantation. In addition, indirect ELISA assays showed that repetition of rhBMP2 did not significantly alter the blood level of anti-BMP2 antibody compared with untreated control groups in both subcutaneous and calvarial deliveries. These results suggest that rhBMP2 can be repeatedly used for bone regeneration therapy in the limits of short interval and a specific dose.