利用间充质干细胞（MSC）治疗因创伤肿瘤引起的骨缺损是较有前景的技术，研究证实其可能通过旁分泌细胞外囊泡（EV）发挥主要作用。前期研究发现，人脂肪干细胞来源细胞外囊泡（hADSC-EV）可以通过表面修饰的方式提高骨修复材料血管化与成骨能力，但hADSC-EV存在提取花费高与产率低的不足，同时其促血管化能力仍需改善。通过连续挤压脂肪干细胞的方式制备的工程化纳米囊泡（hADSC-EN）理论上具有制备效率高的优点，同时预实验结果证实其较hADSC-EV具有潜在更强的促血管化效应。据此，申请人提出构建hADSC-EN自组装表面修饰材料治疗骨缺损的新方法。将hADSC-EN利用生物素-亲和素吸附原理对立体多孔胶原表面进行自组装修饰，对比hADSC-EV，在大鼠颅骨缺损模型中研究其骨再生优势。最后通过MAPK、AKT等经典通路阐明hADSC-EN促进血管化的机制。

The use of mesenchymal stem cells (MSCs) to treat bone defects caused by trauma or tumors is a promising technique. Studies have confirmed that they may play a major role through paracrine extracellular vesicles (EV). Previous studies have found that extracellular vesicles derived from human adipose stem cells (hADSC-EV) can improve the vascularization and osteogenesis ability of bone repair materials through surface modification, but hADSC-EV has the disadvantages of high extraction cost and low yield. Its ability to promote vascularization still needs to be improved. The engineered nanovesicles prepared by serial extrusion of adipose stem cells (hADSC-EN) theoretically have the advantage of high preparation efficiency. At the same time, the pre-experimental results confirmed that it has a potentially stronger angiogenic effect than hADSC-EV. Accordingly, the applicant proposes to construct a new method of hADSC-EN self-assembled surface modification materials to treat bone defects. We will use biotin-avidin adsorption principle to self-assemble modify three-dimensional porous collagen scaffold with hADSC-EN. Compared with hADSC-EV, hADSC-EN’s bone regeneration advantages are studied in the rat skull defect model. Finally, through the classical pathways such as MAPK and AKT, elucidate the mechanism of hADSC-EN to promote vascularization.