Hypoxia-mimicking 3D bioglass-nanoclay scaffolds promote endogenous bone regeneration

• Published in: Bioactive materials 2021-10, Vol.6 (10), p.3485-3495
• Main Authors: Zheng, Xiao, Zhang, Xiaorong, Wang, Yingting, Liu, Yangxi, Pan, Yining, Li, Yijia, Ji, Man, Zhao, Xueqin, Huang, Shengbin, Yao, Qingqing
• Format: Article
• Language: English
• Subjects: 3D bioglass scaffold; Angiogenesis; Endogenous bone regeneration; Hypoxia; Osteogenesis
• ISSN: 2452-199X; 2452-199X
• DOI: 10.1016/j.bioactmat.2021.03.011

Large bone defect repair requires biomaterials that promote angiogenesis and osteogenesis. In present work, a nanoclay (Laponite, XLS)-functionalized 3D bioglass (BG) scaffold with hypoxia mimicking property was prepared by foam replication coupled with UV photopolymerization methods. Our data revealed that the incorporation of XLS can significantly promote the mechanical property of the scaffold and the osteogenic differentiation of human adipose mesenchymal stem cells (ADSCs) compared to the properties of the neat BG scaffold. Desferoxamine, a hypoxia mimicking agent, encourages bone regeneration via activating hypoxia-inducible factor-1 alpha (HIF-1α)-mediated angiogenesis. GelMA-DFO immobilization onto BG-XLS scaffold achieved sustained DFO release and inhibited DFO degradation. Furthermore, in vitro data demonstrated increased HIF-1α and vascular endothelial growth factor (VEGF) expressions on human adipose mesenchymal stem cells (ADSCs). Moreover, BG-XLS/GelMA-DFO scaffolds also significantly promoted the osteogenic differentiation of ADSCs. Most importantly, our in vivo data indicated BG-XLS/GelMA-DFO scaffolds strongly increased bone healing in a critical-sized mouse cranial bone defect model. Therefore, we developed a novel BG-XLS/GelMA-DFO scaffold which can not only induce the expression of VEGF, but also promote osteogenic differentiation of ADSCs to promote endogenous bone regeneration. [Display omitted] ●A nanoclay-functionalized 3D bioglass scaffolds with hypoxia mimicking ability were developed.●These scaffolds had the ability to sustain release of DFO and induce VEGF expression in ADSCs.●Nanoclay together with bioglass promoted the osteogenic differentiation of ADSCs in vitro and cranial bone formation in vivo.●The scaffolds could act as favorable synthetic ECM for large bone defect repair.