Spatiotemporal regulation of injectable heterogeneous silk gel scaffolds for accelerating guided vertebral repair

Osteoporotic vertebral fracture has been jeopardizing the health of the aged population around the world, while the hypoxia microenvironment and oxidative damage of bone defect make it difficult to perform effective tissue regeneration. The balance of oxidative stress and the coupling of vessel and bone ingrowth are critical for bone regeneration. In this study, the injectable heterogeneous silk gel scaffold which can spatiotemporally and sustainedly release bone mesenchymal stem cell-derived small extracellular vesicles (BMSC-sEVs), HIF-1α pathway activator (DFO) and inhibitor (YC-1) was developed for bone repair and vertebral reinforcement. The initial enhancement of HIF-1α upregulated the expression of VEGF to promote angiogenesis; and the balance of Reactive Oxygen Species (ROS) level was regulated to effectively eliminate oxidative damage and abnormal microenvironment. The subsequent inhibition of HIF-1α avoided the overexpression of VEGF and vascular overgrowth. Meanwhile, complex macroporous structures and suitable mechanical support could be obtained within the silk gel scaffolds, which would promote in-situ bone regeneration. Our findings provide a new clinical translation strategy for osteoporotic vertebral augmentation on basis of hypoxia microenvironment improvement. This article is protected by copyright. All rights reserved.

Angiogenesis; Bone regeneration; HIF-1α stabilization; Injectable heterogeneous silk gel scaffold; Spatiotemporal sustained drug release; Vertebral augmentation.