Desktop-stereolithography 3D printing of a radially oriented extracellular matrix/mesenchymal stem cell exosome bioink for osteochondral defect regeneration
Desktop-stereolithography 3D printing of a radially oriented extracellular matrix/mesenchymal stem cell exosome bioink for osteochondral defect regeneration
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用于骨软骨缺损再生的径向定向细胞外基质/间充质干细胞外泌体生物墨水的桌面立体光刻 3D 打印
DOI：
10.7150/thno.31017
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发表时间：
2019-01-01
期刊：
影响因子：
12.4
通讯作者：
Lin, Xianfeng
中科院分区：
文献类型：
--
作者：
Chen, Pengfei;Zheng, Lin;Lin, Xianfeng
线粒体功能障碍和氧化应激损伤是骨关节炎(OA)的特征。间充质干细胞(MSC)来源的外切体在细胞间线粒体通讯中起着重要作用。然而，利用MSC外切体来调节骨性关节炎患者的线粒体功能尚未见报道。本研究旨在探讨骨髓间充质干细胞外切体在三维(3D)打印支架中用于早期骨性关节炎治疗的疗效。方法：我们首先检测了正常人和骨性关节炎患者软骨中的线粒体相关蛋白，并研究了MSC外切体在体外是否能促进线粒体的生物发生。随后，我们设计了一种用于MSC胞外体输送的生物支架，并利用桌面立体光刻技术制备了具有径向通道的3D打印软骨细胞外基质(ECM)/明胶甲基丙烯酸酯(GelMA)/胞外体支架。最后，用兔模型评价3D打印支架的骨软骨修复能力。结果：ECM/GelMA/Exosome支架可有效修复软骨细胞线粒体功能障碍，促进软骨细胞迁移，并使滑膜巨噬细胞向M2表型分化。3D打印支架明显促进了动物模型的软骨再生。结论：3D打印、辐射定向的ECM/GelMA/Exosome支架有望成为治疗早期骨性关节炎的一种有前途的策略。
Mitochondrial dysfunction and oxidative stress damage are hallmarks of osteoarthritis (OA). Mesenchymal stem cell (MSC)-derived exosomes are important in intercellular mitochondria communication. However, the use of MSC exosomes for regulating mitochondrial function in OA has not been reported. This study aimed to explore the therapeutic effect of MSC exosomes in a three dimensional (3D) printed scaffold for early OA therapeutics. Methods: We first examined the mitochondria-related proteins in normal and OA human cartilage samples and investigated whether MSC exosomes could enhance mitochondrial biogenesis in vitro. We subsequently designed a bio-scaffold for MSC exosomes delivery and fabricated a 3D printed cartilage extracellular matrix (ECM)/gelatin methacrylate (GelMA)/exosome scaffold with radially oriented channels using desktop-stereolithography technology. Finally, the osteochondral defect repair capacity of the 3D printed scaffold was assessed using a rabbit model. Results: The ECM/GelMA/exosome scaffold effectively restored chondrocyte mitochondrial dysfunction, enhanced chondrocyte migration, and polarized the synovial macrophage response toward an M2 phenotype. The 3D printed scaffold significantly facilitated the cartilage regeneration in the animal model. Conclusion: This study demonstrated that the 3D printed, radially oriented ECM/GelMA/exosome scaffold could be a promising strategy for early OA treatment.