Zeynep Bal1, Feza Korkusuz2, Hiroyuki Ishiguro3, Rintaro Okada4, Junichi Kushioka1, Ryota Chijimatsu5, Joe Kodama1, Daisuke Tateiwa1, Yuichiro Ukon1, Shinichi Nakagawa1, Eda Çiftci Dede6, Merve Gizer7, Petek Korkusuz8, Hideki Yoshikawa9, Takashi Kaito10. 1. Osaka University, Graduate School of Medicine, Orthopaedic Surgery, 2-2 Yamadaoka, Suita, Osaka 565-0871, Japan. 2. Department of Sports Medicine, Medical Faculty, Hacettepe University, Ankara, Turkey. 3. Department of Orthopaedic Surgery, National Hospital Organization Osaka National Hospital, Osaka, Japan. 4. Department of Orthopaedic Surgery, Minoh City Hospital, Osaka, Japan. 5. The University of Tokyo, Graduate School of Medicine, Bone and Cartilage Regenerative Medicine, Tokyo, Japan. 6. Department of Bioengineering, Graduate School of Science and Engineering, Hacettepe University, Ankara, Turkey. 7. Department of Stem Cell Sciences, Graduate School of Health Sciences, Hacettepe University, Ankara, Turkey. 8. Department of Histology & Embryology, Medical Faculty, Hacettepe University, Ankara, Turkey. 9. Department of Orthopaedic Surgery, Toyonaka Municipal Hospital, Osaka, Japan. 10. Osaka University, Graduate School of Medicine, Orthopaedic Surgery, 2-2 Yamadaoka, Suita, Osaka 565-0871, Japan. Electronic address: takashikaito@ort.med.osaka-u.ac.jp.
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.
BACKGROUND: Efficient bone regeneration using recombinant humanbone 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 osteogenicnano-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.
Authors: Christian Deininger; Andrea Wagner; Patrick Heimel; Elias Salzer; Xavier Monforte Vila; Nadja Weißenbacher; Johannes Grillari; Heinz Redl; Florian Wichlas; Thomas Freude; Herbert Tempfer; Andreas Herbert Teuschl-Woller; Andreas Traweger Journal: Int J Mol Sci Date: 2021-12-28 Impact factor: 5.923