Spatiotemporal regulation of angiogenesis/osteogenesis emulating natural bone healing cascade for vascularized bone formation

Journal of Nanobiotechnology

Huimin Tao¹  Fangqian Wang¹  Xingzhi Zhou¹  Jiayu Chen¹  Wei Zhang¹  An Liu¹  Wangsiyuan Teng¹  Peng Lin¹  Yan Wu¹  Hangxiang Sun¹  Xianan Mo¹  Xiaohua Yu¹  Zengjie Zhang¹  Zhaoming Ye¹  Donghua Huang¹  Yikai Wang²  Yuxiao Ye³ 

[1] Department of Orthopedic Surgery, The Second Affiliated Hospital, Zhejiang University School of Medicine, 310000, Hangzhou, Zhejiang, People’s Republic of China;Orthopedics Research Institute of Zhejiang University, 310000, Hangzhou, Zhejiang, People’s Republic of China;Key Laboratory of Motor System Disease Research and Precision Therapy of Zhejiang Province, 310000, Hangzhou, Zhejiang, People’s Republic of China;Department of Orthopedics, Renming Hospital of Wuhan University, Gaoxin 6th Road, 430000, Wuhan, Hubei, People’s Republic of China;School of Material Science and Engineering, University of New South Wales, 2052, Sydney, Australia;

关键词: Hydrogel;    Mineral coating;    Growth factor;    Angiogenesis;    Osteogenesis;   

DOI  :  10.1186/s12951-021-01173-z

来源: Springer

【 摘 要 】

Engineering approaches for growth factor delivery have been considerably advanced for tissue regeneration, yet most of them fail to provide a complex combination of signals emulating a natural healing cascade, which substantially limits their clinical successes. Herein, we aimed to emulate the natural bone healing cascades by coupling the processes of angiogenesis and osteogenesis with a hybrid dual growth factor delivery system to achieve vascularized bone formation. Basic fibroblast growth factor (bFGF) was loaded into methacrylate gelatin (GelMA) to mimic angiogenic signalling during the inflammation and soft callus phases of the bone healing process, while bone morphogenetic protein-2 (BMP-2) was bound onto mineral coated microparticles (MCM) to mimics osteogenic signalling in the hard callus and bone remodelling phases. An Initial high concentration of bFGF accompanied by a sustainable release of BMP-2 and inorganic ions was realized to orchestrate well-coupled osteogenic and angiogenic effects for bone regeneration. In vitro experiments indicated that the hybrid hydrogel markedly enhanced the formation of vasculature in human umbilical vein endothelial cells (HUVECs), as well as the osteogenic differentiation of mesenchymal stem cells (BMSCs). In vivo results confirmed the optimal osteogenic performance of our F/G-B/M hydrogel, which was primarily attributed to the FGF-induced vascularization. This research presents a facile and potent alternative for treating bone defects by emulating natural cascades of bone healing.Graphical Abstract

【 授权许可】

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