Engineered Exosome-Functionalized Extracellular Matrix-Mimicking Hydrogel for Promoting Bone Repair in Glucocorticoid-Induced Osteonecrosis of the Femoral Head
Engineered Exosome-Functionalized Extracellular Matrix-Mimicking Hydrogel for Promoting Bone Repair in Glucocorticoid-Induced Osteonecrosis of the Femoral Head
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DOI：
10.1021/acsami.3c01539
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发表时间：
2023-06-12
影响因子：
9.5
通讯作者：
Kang, Pengde
中科院分区：
文献类型：
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作者：
Chen, Changjun;Fu, Li;Kang, Pengde
糖皮质激素诱导的股骨头骨坏死（GC-ONFH）是一种严重的骨病，通常影响年轻人。临床治疗GC-ONFH主要采用植骨联合核心减压。然而，结果通常不像预期的那样令人满意。在这里，我们报道了一种工程外泌体功能化的模拟外细胞基质的水凝胶，用于促进GC-ONFH中的骨修复。与Con-Exo相比，常规培养基中由骨髓干细胞分泌的外泌体在锂离子刺激下促进巨噬细胞M2极化，抑制巨噬细胞M1极化。此外，由于水凝胶可以作为外泌体的理想载体，促进其持续释放以提高治疗效率和体内应用，因此采用由甲基丙烯酰化I型胶原组成的细胞外基质（ECM）模拟水凝胶（Lightgel）将Li-Exo/Con-Exo结合构建lighgel -Li-Exo水凝胶/ lighgel - con - exowater凝胶。体外研究表明，lighgel - li - exo水凝胶具有最显著的促成骨和促血管生成活性。最后，我们评估了水凝胶对GC-ONFH大鼠模型的治疗效果。结果表明，在GC-ONFH中，lighgel - li - exo水凝胶对巨噬细胞M2极化、成骨和血管生成促进骨修复的作用最为显著。综上所述，这种新型工程外泌体功能化的模拟ecm的水凝胶可能是一种很有前途的骨坏死治疗策略。
Glucocorticoid-inducedosteonecrosis of the femoral head (GC-ONFH)is a serious bone disease that often affects young individuals. Bonegrafting combined with core decompression is mainly used in the clinicto treat GC-ONFH. However, the outcome is usually not satisfactory,as expected. Here, we report an engineered exosome-functionalizedextracellular matrix-mimicking hydrogel for promoting bone repairin GC-ONFH. Compared with Con-Exo, exosomes secreted by bone marrowstem cells (BMSCs) in conventional culture medium, the engineeredLi-Exo, exosomes derived from bone marrow stem cells (BMSCs) stimulatedby lithium ions, promoted macrophage M2 polarization while inhibitingmacrophage M1 polarization. Furthermore, inspired by the fact thathydrogels can serve as desirable carriers of exosomes to facilitatetheir release in a sustained manner for improved therapeutic efficiencyand in vivo application, an extracellular matrix (ECM)-mimicking hydrogel(Lightgel) composed of methacryloylated type I collagen was employedto incorporate Li-Exo/Con-Exo to construct the Lightgel-Li-Exo hydrogel/Lightgel-Con-Exohydrogel. In vitro studies showed that the Lightgel-Li-Exo hydrogelhad the most significant pro-osteogenic and pro-angiogenic activity.Finally, we evaluated the therapeutic effects of the hydrogel in ratmodels of GC-ONFH. As a result, the Lightgel-Li-Exo hydrogel had themost significant effect on enhancing macrophage M2 polarization, osteogenesis,and angiogenesis to promote bone repair in GC-ONFH. Taken together,this novel engineered exosome-functionalized ECM-mimicking hydrogelcould be a promising strategy for osteonecrosis treatment.