间充质干细胞
化学
去细胞化
脚手架
细胞生物学
微泡
脐静脉
再生医学
再生(生物学)
骨髓
生物医学工程
骨愈合
体内
组织工程
归巢(生物学)
骨组织
新生血管
干细胞
血管生成
微泡
骨细胞
间质细胞
体外
血管生成
氧气张力
祖细胞
细胞外基质
人脐静脉内皮细胞
外体
作者
Lei Zhu,Ji Wang,Zhengwei Liu,Kai Chen,Zhuhao Wu,Yongxiang Wang
标识
DOI:10.1186/s12951-025-03961-3
摘要
Tissue engineering scaffolds remain pivotal in bone defect repair. Contemporary research in this field predominantly focuses on enhancing bone regeneration by optimizing scaffold composition and structure, and incorporating bioactive components. Herein, we developed a decellularized fish bone (DFB) scaffold integrated with hypoxia-osteogenic exosomes (HO-Exos), derived from rat bone marrow mesenchymal stem cells (BMSCs) cultured under 5% oxygen tension with 7-day osteogenic priming, to promote osseous repair via their synergistic effect. The hierarchical porosity of DFB scaffolds creates a biomimetic microenvironment conducive to BMSC adhesion and osteogenic mineralization. Functionally, HO-Exos stimulate osteogenic differentiation of BMSCs via modulation of the Wnt/β-catenin pathway, enhance cellular migration, and promote tubulogenesis in human umbilical vein endothelial cells (HUVECs). These vesicles synergistically potentiate vascularized bone regeneration in vivo through coordinated osteogenic-angiogenic regulation. To achieve sustained therapeutic delivery, HO-Exos were encapsulated within DFB scaffolds, leveraging their structural network for tailored release kinetics. In a rat model of critical-sized femoral metaphyseal defects, the designed scaffolds exhibited significant improvements in both neovascularization density and bone volume fraction compared to controls. These findings underscore the potential of exosome-functionalized biomimetic scaffolds for treating bone defects.
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