Modification of adipose mesenchymal stem cells-derived small extracellular vesicles with fibrin-targeting peptide CREKA for enhanced bone repair.
Modification of adipose mesenchymal stem cells-derived small extracellular vesicles with fibrin-targeting peptide CREKA for enhanced bone repair.
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DOI：
10.1016/j.bioactmat.2022.05.031
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发表时间：
2023-03
影响因子：
18.9
通讯作者：
Wang, Yingjun
中科院分区：
文献类型：
--
作者：
Wu, Qi;Fu, Xiaoling;Li, Xian;Li, Jing;Han, Weiju;Wang, Yingjun
骨修复过程受到大量生物活性因子的高度调控。因此，向缺损部位补充生物活性因子的“鸡尾酒”是骨修复的理想选择。在这方面，来自间充质干细胞的小细胞外囊泡（sev）在组织修复中具有很大的潜力。然而，sev的归巢性和保留性差极大地限制了其临床应用的可能性。在本研究中，我们将DMPE-PEG-CREKA插入到脂肪源性间充质干细胞释放的sev膜中，获得CREKA功能化的sev (CREKA- sev)，它可以靶向纤维蛋白在骨缺损中积累和保留。我们的研究结果表明，creka - sev与sev一样，能够促进BMSCs的成骨分化，增强HUVECs的血管生成能力，并调节巨噬细胞的极化。此外，由于creka - sev改善了纤维蛋白结合和保留能力，它们在大鼠股骨缺损模型中显著增强了骨修复。本研究为提高sev的治疗效果提供了新的策略，表明creka - sev在骨组织修复中具有很大的应用价值。归巢和保留能力差极大地限制了MSCs衍生sev的临床应用。CREKA修饰使sev能够有效结合纤维蛋白，促进其在骨缺损中的积累和保留。CREKA-sEVs在大鼠股骨缺损模型中显著增强骨修复。
The process of bone repair is highly regulated by a large number of bioactive factors. Thus, a “cocktail” of bioactive factors supplemented to the defect sites is desirable for bone repair. In this regard, small extracellular vesicles (sEVs) derived from mesenchymal stem cells hold great potential in tissue repair. Nevertheless, the poor homing and retention of sEVs greatly limited their possible clinical application. In the present work, DMPE-PEG-CREKA was inserted into the membrane of sEVs released from adipose-derived mesenchymal stem cells to obtain CREKA functionalized sEVs (CREKA-sEVs), which could target fibrin to accumulate and retain in bone defects. Our results showed that CREKA-sEVs, like sEVs, promoted the osteogenic differentiation of BMSCs, the angiogenic property of HUVECs, and modulated the polarization of macrophages in vitro. Furthermore, due to the improved fibrin-binding and retention capacity of CREKA-sEVs, they enhanced the bone repair substantially in the rat femoral defect model. This study provided a new strategy to improve the therapeutic efficiency of sEVs and showed that CREKA-sEVs had great application value in bone tissue repair. The poor homing and retention capacity greatly limited the possible clinical application of sEVs derived from MSCs. CREKA modification enabled sEVs to bind fibrin effectively and promoted their accumulation and retention in bone defects. CREKA-sEVs enhanced bone repair substantially in the rat femoral defect model.
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