Yang Shuo, Zhu Biao, Yin Peng, Zhao Lisheng, Wang Yizhu, Fu Zhiguang, Dang Ruijie, Xu Juan, Zhang Jianjun, Wen Ning
Department of Stomatology, Chinese PLA General Hospital, Beijing 100853, China.
College of Chemical Engineering, Beijing University of Chemical Technology, Beijing 100029, China.
ACS Biomater Sci Eng. 2020 Mar 9;6(3):1590-1602. doi: 10.1021/acsbiomaterials.9b01363. Epub 2020 Feb 18.
The treatment of bone defects has plagued clinicians. Exosomes, the naturally secreted nanovesicles by cells, exhibit great potential in bone defect regeneration to realize cell-free therapy. In this work, we successfully revealed that human umbilical cord mesenchymal stem cells-derived exosomes could effectively promote the proliferation, migration, and osteogenic differentiation of a murine calvariae preosteoblast cell line in vitro. Considering the long period of bone regeneration, to effectively exert the reparative effect of exosomes, we synthesized an injectable hydroxyapatite (HAP)-embedded in situ cross-linked hyaluronic acid-alginate (HA-ALG) hydrogel system to durably retain exosomes at the defect sites. Then, we combined the exosomes with the HAP-embedded in situ cross-linked HA-ALG hydrogel system to repair bone defects in rats in vivo. The results showed that the combination of exosomes and composite hydrogel could significantly enhance bone regeneration. Our experiment provides a new strategy for exosome-based therapy, which shows great potential in future tissue and organ repair.
骨缺损的治疗一直困扰着临床医生。外泌体是细胞自然分泌的纳米囊泡，在骨缺损再生中具有巨大潜力，可实现无细胞治疗。在这项工作中，我们成功揭示了人脐带间充质干细胞来源的外泌体能够在体外有效促进小鼠颅骨前成骨细胞系的增殖、迁移和成骨分化。考虑到骨再生周期长，为有效发挥外泌体的修复作用，我们合成了一种可注射的、嵌入羟基磷灰石（HAP）的原位交联透明质酸-海藻酸盐（HA-ALG）水凝胶系统，以将外泌体持久地保留在缺损部位。然后，我们将外泌体与嵌入HAP的原位交联HA-ALG水凝胶系统相结合，用于体内修复大鼠的骨缺损。结果表明，外泌体与复合水凝胶的组合可显著增强骨再生。我们的实验为基于外泌体的治疗提供了一种新策略，在未来的组织和器官修复中显示出巨大潜力。
