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

概要

〔目的(Purpose)〕
Efficient bone regeneration using recombinant human bone morphogenetic protcin-2 (BMP-2) is needed so as to reduce side effects caused by high-dose BMP-2 use. Synthetic copolymer polylactic-acid polyethylene glycol (PLA-PEG) is known as a good carrier for BMP-2. Osteoconductive properties of nano-sized hydroxyapatite (nHAp) is reported to be superior to conventional hydroxyapatite. The composite material of PLA-PEG (for sustained release) and osteogenic nHAP can contribute to efficient bone regeneration by BMP-2. In the literature no study is reported with PLA-PEG/ BMP-2 / nHAp. So the purpose of this study is to produce a novel biocomposite of PLA-PEG/nHAp/BMP-2 and to investigate the effectiveness of a novel composite material of* PLA-PEG and nHAp as a carrier for BMP-2.

〔方法ならびに成績(Methods/Results)〕
方法[Methods]
The release kinetics of BMP-2 from the composites was investigated by ELISA. Thirty-six males Sprague-Dawley rats underwent posterolateral spinal fusion on L4-5 transverse processes with 3 different doses of BMP-2 (0μg [control],3gg [low dose], 10pg [high dose]). Weekly μCΤ and manual palpation - histology [by Haematoxylin & Eosin (H&E) and Safranin O (SO)] at 8 weeks postoperatively were used to assess spinal fusion.

成績[Results]
ELISA demonstrated the sustained release of BMP-2 from the composite until day 21.gCT and manual palpation results demonstrated a solid fusion in 91.6% (11/12) of specimens in both the low- and high-dose groups. No 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. Histological evaluation with H&E and SO staining was coherent with μCT results. The μCT evaluation of the newly formed bone mass of low- and high-dose BMP-2 groups demonstrated the newly formed fusion mass was larger in size (BV and TV) in the high-dose BMP-2 group, however the low-dose BMP-2 group formed more solid fusion mass with a higher BV/TV value.

〔総括(Conclusion)〕 ·
The novel 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. This novel composite material has potential in clinical applications(spinal fusion, large bone detect and non-union) by enabling efficient bone formation by BMP-2.