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Umbilical Mesenchymal Stem Cell-Derived Exosome-Encapsulated Hydrogels Accelerate Bone Repair by Enhancing Angiogenesis

Yuntong ZhangDepartment of Emergency and Trauma, Changhai Hospital, Naval Medical University, Shanghai 200433, ChinaYang XieDepartment of Orthopaedics, Changhai Hospital, Naval Medical University, Shanghai 200433, ChinaZichen HaoDepartment of Orthopaedics, Affiliated Yantai Yuhuangding Hospital, Qingdao University, Yantai 264000, ChinaPanyu ZhouDepartment of Emergency and Trauma, Changhai Hospital, Naval Medical University, Shanghai 200433, ChinaPanfeng WangDepartment of Emergency and Trauma, Changhai Hospital, Naval Medical University, Shanghai 200433, ChinaShuo FangDepartment of Plastic Surgery, Changhai Hospital, Naval Medical University, Shanghai 200433, ChinaLi LuDepartment of Plastic Surgery, Changhai Hospital, Naval Medical University, Shanghai 200433, ChinaShuogui XuDepartment of Emergency and Trauma, Changhai Hospital, Naval Medical University, Shanghai 200433, ChinaYan XiaDepartment of Emergency and Trauma, Changhai Hospital, Naval Medical University, Shanghai 200433, China

2021en

ABI

Annotatsiya

Repair of large bone defects represents a major challenge for orthopedic surgeons. The newly formed microvessels inside grafts play a crucial role in successful bone tissue engineering. Previously, an active role for mesenchymal stem cell (MSC)-derived exosomes in blood vessel development and progression was suggested in the repair of multiple tissues. However, the reports on the application of MSC-derived exosomes in the repair of large bone defects are sparse. In this study, we encapsulated umbilical MSC-derived exosomes (uMSCEXOs) in hyaluronic acid hydrogel (HA-Gel) and combined them with customized nanohydroxyapatite/poly-ε-caprolactone (nHP) scaffolds to repair cranial defects in rats. Imaging and histological evaluation indicated that the uMSCEXOs/Gel/nHP composites markedly enhanced bone regeneration in vivo, and the uMSCEXOs might play a key role in this process. Moreover, the in vitro results demonstrated that uMSCEXOs promoted the proliferation, migration, and angiogenic differentiation of endothelial progenitor cells (EPCs) but did not significantly affect the osteogenic differentiation of BMSCs. Importantly, mechanistic studies revealed that exosomal miR-21 was the potential intercellular messenger that promoted angiogenesis by upregulating the NOTCH1/DLL4 pathway. In conclusion, our findings exhibit a promising exosome-based strategy in repairing large bone defects through enhanced angiogenesis, which potentially regulated by the miR-21/NOTCH1/DLL4 signaling axis.

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Identifikatorlar

DOI: 10.1021/acsami.0c22671

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