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 mu g [control], 3 mu g [low dose], and 10 mu g [high dose]). Weekly mu CT 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. mu CT 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. (C) 2021 Elsevier Inc. All rights reserved.