A novel nano-hydroxyapatite/synthetic polymer/bone morphogenetic protein-2 composite for efficient bone regeneration

BACKGROUND: Efficient bone regeneration using recombinant human bone morphogenetic protein-2 (BMP-2) is needed to reduce side effects caused by high-dose BMP-2 use. The composite material of polylactic acid–polyethene glycol (PLA-PEG) for sustained release and an osteogenic nano-hydroxyapatite (nHAp) can contribute to efficient bone regeneration by BMP-2. STUDY DESIGN: An experimental in vitro and in vivo study. PURPOSE: The objective of this study is to investigate the effectiveness of a novel composite material of PLA-PEG and nHAp as a carrier for BMP-2. METHODS: The release kinetics of BMP-2 from the composites was investigated by ELISA. Thirty-six male Sprague–Dawley rats underwent posterolateral spinal fusion on L4–L5 with three different doses of BMP-2 (0 µg [control], 3 µg [low dose], and 10 µg [high dose]). Weekly µCT results and histology and a manual palpation test at 8 weeks postoperatively were used for assessment of the spinal fusion. RESULTS: ELISA demonstrated the sustained release of BMP-2 until day 21. µCT and manual palpation test demonstrated a solid fusion in 91.6% (11/12) of specimens in both the low- and high-dose groups. N mice in the control group attained bony fusion (0%, 0/9). nHAp was resorbed between 2 and 4 weeks postoperatively, and regenerated fusion mass at 8 weeks postoperatively consisted of only newly formed bone. CONCLUSIONS: The nHAp/PLA-PEG composite enabled efficient bone regeneration with low-dose BMP-2. The sustained release of BMP-2 by PLA-PEG and the osteogenic and biodegradable scaffold of nHAp might contribute to efficient bone regeneration. CLINICAL SIGNIFICANCE: This novel composite material has potential in clinical applications (spinal fusion, large bone defect and non-union) by enabling efficient bone formation by BMP-2.