Abstract
Sustained release of BMP-2 is reported to be able to reduce the required dose of BMP-2 for bone induction. Nanohydroxyapatite (nHAp) has an osteoinduction capability which is lack in conventional hydroxyapatite. In this study, we combined PLA-PEG with nHAp and investigated the bone regenerative capacity of the newly established composite material of rhBMP-2/PLA-PEG/nHAp in a rat model of spinal fusion. The PLA-PEG was liquidized in acetone and mixed with nHAp and rhBMP-2. The sheet-shaped BMP-2/PLA-PEG (5mg)/nHAp (12.5mg) composites were prepared while evaporating the acetone. The release kinetics of rhBMP-2 from the composite was investigated by ELISA. In vivo bone formation was investigated by posterolateral spinal fusion in rats (the dosage of rhBMP-2; 0µg/ 0.5µg / 3µg). Bone formation was assessed by µCT and histology at post-op. 8 weeks. The composite showed the burst-release in the initial 24 hours (69% of total release) and the subsequent sustained-release for 25 days. According to µCT and histology of the spinal fusion experiment for all groups the bone formation was observed. While no bony bridging was observed in 0 µg and 0.5 µg BMP groups; in 3 µg group bony bridging and fusion were achieved. We developed a new technology for bone regeneration with rhBMP-2/PLA-PEG/nHAp composite. The reduction in the required dose of BMP-2 for bone induction was achieved. This result can be explained by the high bone induction ability of nHAp and sustainable release of BMP from PLA-PEG in the composite.