Institute of Hematology, Union Hospital, Tongji Medical College, Huazhong University of Science and Technology, Wuhan 430022, P. R. China.
Department of Plastic and Reconstructive Surgery, Shanghai 9th People's Hospital, Shanghai Jiao Tong University School of Medicine, Shanghai Key Laboratory of Tissue Engineering, National Tissue Engineering Center of China, Shanghai 200011, P. R. China.
Sci Rep. 2017 Apr 3;7:45622. doi: 10.1038/srep45622.
Vascularization is crucial for bone regeneration after the transplantation of tissue-engineered bone grafts in the clinical setting. Growing evidence suggests that mesenchymal stem cell (MSC)-derived extracellular vesicles (EVs) are potently pro-angiogenic both in vitro and in vivo. In the current study, we fabricated a novel EV-functionalized scaffold with enhanced pro-angiogenic and pro-bone regeneration activities by coating decalcified bone matrix (DBM) with MSC-derived EVs. EVs were harvested from rat bone marrow-derived MSCs and the pro-angiogenic potential of EVs was investigated in vitro. DBM scaffolds were then coated with EVs, and the modification was verified by scanning electron microscopy and confocal microscopy. Next, the pro-angiogenic and pro-bone regeneration activities of EV-modified scaffolds were evaluated in a subcutaneous bone formation model in nude mice. Micro-computed tomography scanning analysis showed that EV-modified scaffolds with seeded cells enhanced bone formation. Enhanced bone formation was confirmed by histological analysis. Immunohistochemical staining for CD31 proved that EV-modified scaffolds promoted vascularization in the grafts, thereby enhancing bone regeneration. This novel scaffold modification method provides a promising way to promote vascularization, which is essential for bone tissue engineering.
血管生成对于组织工程骨移植物在临床环境中的骨再生至关重要。越来越多的证据表明，间充质干细胞（MSC）衍生的细胞外囊泡（EV）在体外和体内都具有强大的促血管生成作用。在本研究中，我们通过用 MSC 衍生的 EV 涂覆脱钙骨基质（DBM）来制造一种具有增强的促血管生成和促骨再生活性的新型 EV 功能化支架。从大鼠骨髓来源的 MSC 中收获 EV，并在体外研究 EV 的促血管生成潜力。然后用 EV 涂覆 DBM 支架，并通过扫描电子显微镜和共聚焦显微镜验证修饰。接下来，在裸鼠皮下骨形成模型中评估 EV 修饰支架的促血管生成和促骨再生活性。微计算机断层扫描分析显示，接种细胞的 EV 修饰支架增强了骨形成。组织学分析证实了增强的骨形成。CD31 的免疫组织化学染色证明，EV 修饰的支架促进了移植物中的血管生成，从而增强了骨再生。这种新型支架修饰方法为促进血管生成提供了一种有前途的方法，这对于骨组织工程至关重要。
