Spatiotemporalized Hydrogel Microspheres Promote Vascularized Osteogenesis via Ultrasound Oxygen Delivery
Spatiotemporalized Hydrogel Microspheres Promote Vascularized Osteogenesis via Ultrasound Oxygen Delivery
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DOI：
10.1002/adfm.202308205
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发表时间：
2023-09
影响因子：
19
通讯作者：
Shuyu Chen;Xiao Han;Yang Cao;Weiwei Yi;Yi Zhu;Xiaoqian Ding;Kai Li;Jieliang Shen;Wenguo Cui;Ding-zhen Bai
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文献类型：
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作者：
Shuyu Chen;Xiao Han;Yang Cao;Weiwei Yi;Yi Zhu;Xiaoqian Ding;Kai Li;Jieliang Shen;Wenguo Cui;Ding-zhen Bai
时空氧平衡紊乱是导致大面积骨缺损延迟愈合或不愈合的主要原因。准确的氧管理，以调节中断的时空氧平衡在9小时的缺氧是骨组织再生的必要条件。本文通过微流控技术将双乳化法制备的载氧纳米气泡成功包埋在GelMA/HepMA微球大分子网络中，并通过非共价结合骨形态发生蛋白2（BMP-2）构建时空化的水凝胶微球。时空化水凝胶微球在骨损伤后9 h通过超声在体外精确“遥控”氧释放，以调节时空氧稳态紊乱，维持高水平的血管内皮生长因子（VEGF）表达，加速骨修复。时空化水凝胶微球具有良好的携氧能力和超声响应性，在1、2、3和4 W不同强度的超声作用下，氧浓度分别增加到1.63、1.95、2.11和2.29倍，为超声精确调控时空氧平衡紊乱提供了条件。在体外缺氧模型和体内大鼠股骨缺损模型中，时空水凝胶微球均表现出良好的血管化和成骨能力，为临床治疗大面积骨缺损提供了新的策略。
Disturbance of spatiotemporal oxygen balance is the main cause of delayed healing or nonhealing of large bone defects. The accurate administration of oxygen to regulate disruptions in the spatiotemporal oxygen equilibrium during 9 h of hypoxia is imperative for bone tissue regeneration. Herein, oxygen‐loaded nanobubbles prepared by double emulsification are successfully embedded in GelMA/HepMA microsphere macromolecular meshwork by microfluidic techniques, and a spatiotemporalized hydrogel microsphere is constructed by noncovalently binding bone morphogenetic protein 2 (BMP‐2). The spatiotemporalized hydrogel microspheres precisely “remote control” oxygen release by ultrasound in vitro 9 h after bone injury to regulate spatiotemporal oxygen homeostasis disorder, maintain a high level of vascular endothelial growth factor (VEGF) expression, and accelerate bone repair. The spatiotemporalized hydrogel microspheres possess good oxygen‐carrying capacity and ultrasonic responsiveness, and the oxygen concentration increases to 1.63, 1.95, 2.11, and 2.29 times under the ultrasound action at different intensities of 1, 2, 3, and 4 W, respectively, providing the conditions for the precise regulation of spatiotemporal oxygen balance disorder by ultrasound. In the in vitro hypoxia model and in vivo rat femoral defect model, the spatiotemporal hydrogel microspheres show good vascularization and osteogenesis capabilities, which provide a new strategy for the clinical treatment of large bone defects.