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

Zeynep Bal, Feza Korkusuz, Hiroyuki Ishiguro, Rintaro Okada, Junichi Kushioka, Ryota Chijimatsu, Joe Kodama, Daisuke Tateiwa, Yuichiro Ukon, Shinichi Nakagawa, Eda Çiftci Dede, Merve Gizer, Petek Korkusuz, Hideki Yoshikawa, Takashi Kaito

Research output: Contribution to journalArticlepeer-review

14 Citations (Scopus)

Abstract

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.

Original languageEnglish
Pages (from-to)865-873
Number of pages9
JournalSpine Journal
Volume21
Issue number5
DOIs
Publication statusPublished - May 2021
Externally publishedYes

Keywords

  • Biomaterials
  • Bone morphogenetic protein
  • Bone regeneration
  • Nano-hydroxyapatite
  • Spinal fusion
  • Synthetic polymer

ASJC Scopus subject areas

  • Surgery
  • Orthopedics and Sports Medicine
  • Clinical Neurology

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