Guan Pengfei, Liu Can, Xie Denghui, Mao Shichao, Ji Yuelun, Lin Yongchang, Chen Zheng, Wang Qiyou, Fan Lei, Sun Yongjian
Department of Pediatric Orthopedic, Center for Orthopedic Surgery, The Third Affiliated Hospital of Southern Medical University, Guangzhou, 510515, China.
Department of Orthopedic Surgery, The First Affiliated Hospital, Zhejiang University School of Medicine, Hangzhou, 310003, China.
Bioact Mater. 2021 Sep 16;10:145-158. doi: 10.1016/j.bioactmat.2021.09.010. eCollection 2022 Apr.
Growth plate cartilage has limited self-repair ability, leading to poor bone bridge formation post-injury and ultimately limb growth defects in children. The current corrective surgeries are highly invasive, and outcomes can be unpredictable. Following growth plate injury, the direct loss of extracellular matrix (ECM) coupled with further ECM depletion due to the inhibitory effects of inflammation on the cartilage matrix protein greatly hinder chondrocyte regeneration. We designed an exosome (Exo) derived from bone marrow mesenchymal stem cells (BMSCs) loaded ECM-mimic hydrogel to promote cartilage repair by directly supplementing ECM and anti-inflammatory properties. Aldehyde-functionalized chondroitin sulfate (OCS) was introduced into gelatin methacryloyl (GM) to form GMOCS hydrogel. Our results uncovered that GMOCS hydrogel could significantly promote the synthesis of ECM due to the doping of OCS. In addition, the GMOCS-Exos hydrogel could further promote the anabolism of chondrocytes by inhibiting inflammation and ultimately promote growth plate injury repair through ECM remodeling.
生长板软骨的自我修复能力有限，导致损伤后骨桥形成不佳，最终导致儿童肢体生长缺陷。目前的矫正手术具有高度侵入性，且结果可能不可预测。生长板损伤后，细胞外基质（ECM）的直接损失以及由于炎症对软骨基质蛋白的抑制作用导致的ECM进一步消耗，极大地阻碍了软骨细胞的再生。我们设计了一种源自骨髓间充质干细胞（BMSC）的外泌体（Exo）负载的ECM模拟水凝胶，通过直接补充ECM和抗炎特性来促进软骨修复。将醛基功能化硫酸软骨素（OCS）引入甲基丙烯酰化明胶（GM）中形成GMOCS水凝胶。我们的结果表明，由于OCS的掺杂，GMOCS水凝胶可以显著促进ECM的合成。此外，GMOCS-Exos水凝胶可以通过抑制炎症进一步促进软骨细胞的合成代谢，并最终通过ECM重塑促进生长板损伤修复。
