Nanoclay gels attenuate BMP2-associated inflammation and promote chondrogenesis to enhance BMP2-spinal fusion.

Autor:	Furuichi T; Department of Orthopedic Surgery, Osaka University Graduate School of Medicine, 2-2 Yamadaoka, Suita, Osaka, 565-0871, Japan., Hirai H; Department of Orthopedic Surgery, Osaka University Graduate School of Medicine, 2-2 Yamadaoka, Suita, Osaka, 565-0871, Japan., Kitahara T; Department of Orthopedic Surgery, Osaka University Graduate School of Medicine, 2-2 Yamadaoka, Suita, Osaka, 565-0871, Japan., Bun M; Department of Orthopedic Surgery, Osaka University Graduate School of Medicine, 2-2 Yamadaoka, Suita, Osaka, 565-0871, Japan., Ikuta M; Department of Orthopedic Surgery, Osaka University Graduate School of Medicine, 2-2 Yamadaoka, Suita, Osaka, 565-0871, Japan., Ukon Y; Department of Orthopedic Surgery, Osaka University Graduate School of Medicine, 2-2 Yamadaoka, Suita, Osaka, 565-0871, Japan., Furuya M; Department of Orthopedic Surgery, Osaka University Graduate School of Medicine, 2-2 Yamadaoka, Suita, Osaka, 565-0871, Japan., Oreffo ROC; Bone & Joint Research Group, Centre for Human Development, Stem Cells & Regeneration, Institute of Developmental Sciences, University of Southampton, Southampton, SO16 6YD, United Kingdom., Janeczek AA; Renovos Biologics Limited, 2 Venture Road, University of Southampton Science Park, Southampton, SO16 7NP, United Kingdom., Dawson JI; Bone & Joint Research Group, Centre for Human Development, Stem Cells & Regeneration, Institute of Developmental Sciences, University of Southampton, Southampton, SO16 6YD, United Kingdom., Okada S; Department of Orthopedic Surgery, Osaka University Graduate School of Medicine, 2-2 Yamadaoka, Suita, Osaka, 565-0871, Japan., Kaito T; Department of Orthopedic Surgery, Osaka University Graduate School of Medicine, 2-2 Yamadaoka, Suita, Osaka, 565-0871, Japan.
Jazyk:	angličtina
Zdroj:	Bioactive materials [Bioact Mater] 2024 Nov 05; Vol. 44, pp. 474-487. Date of Electronic Publication: 2024 Nov 05 (Print Publication: 2025).
DOI:	10.1016/j.bioactmat.2024.10.027
Abstrakt:	Bone morphogenetic protein 2 (BMP2) is clinically applied for treating intractable fractures and promoting spinal fusion because of its osteogenic potency. However, adverse effects following the release of supraphysiological doses of BMP2 from collagen carriers are widely reported. Nanoclay gel (NC) is attracting attention as a biomaterial, given the potential for localized efficacy of administered agents. However, the efficacy and mechanism of action of NC/BMP2 remain unclear. This study explored the efficacy of NC as a BMP2 carrier in bone regeneration and the enhancement mechanism. Subfascial implantation of NC containing BMP2 elicited superior bone formation compared with collagen sponge (CS). Cartilage was uniformly formed inside the NC, whereas CS formed cartilage only on the perimeter. Additionally, CS induced a dose-dependent inflammatory response around the implantation site, whereas NC induced a minor response, and inflammatory cells were observed inside the NC. In a rat spinal fusion model, NC promoted high-quality bony fusion compared to CS. In vitro, NC enhanced chondrogenic and osteogenic differentiation of hBMSCs and ATDC5 cells while inhibiting osteoclastogenesis. Overall, NC/BMP2 facilitates spatially controlled, high-quality endochondral bone formation without BMP2-induced inflammation and promotes high-density new bone, functioning as a next-generation BMP2 carrier. Competing Interests: The authors declare the following financial interests/personal relationships which may be considered as potential competing interests: Takashi Kaito has received research funding from 10.13039/501100001691Japan Society for the Promotion of Science and Biosciencepartners Inc.R.O.C. Oreffo, J. I Dawson and A.A. Janeczek are co-founders and shareholders in a University of Southampton spin out company, Renovos Biologics Limited, with a license to IP indirectly related to the current manuscript. (© 2024 The Authors.)
Databáze:	MEDLINE
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