Cui Jing, Ning Liang-Ju, Wu Fei-Peng, Hu Ruo-Nan, Li Xuan, He Shu-Kun, Zhang Yan-Jing, Luo Jia-Jiao, Luo Jing-Cong, Qin Ting-Wu
Laboratory of Stem Cell and Tissue Engineering, Orthopedic Research Institute, State Key Laboratory of Biotherapy and Cancer Center, West China Hospital, Sichuan University and Collaborative Innovation Center of Biotherapy, Chengdu, China.
Department of Orthopedic Surgery, West China Hospital, Sichuan University, Chengdu, China.
NPJ Regen Med. 2022 Apr 26;7(1):26. doi: 10.1038/s41536-022-00220-z.
Tendon regeneration highly relies on biomechanical and biochemical cues in the repair microenvironment. Herein, we combined the decellularized bovine tendon sheet (DBTS) with extracellular matrix (ECM) from tendon-derived stem cells (TDSCs) to fabricate a biomechanically and biochemically functional scaffold (tECM-DBTS), to provide a functional and stem cell ECM-based microenvironment for tendon regeneration. Our prior study showed that DBTS was biomechanically suitable to tendon repair. In this study, the biological function of tECM-DBTS was examined in vitro, and the efficiency of the scaffold for Achilles tendon repair was evaluated using immunofluorescence staining, histological staining, stem cell tracking, biomechanical and functional analyses. It was found that tECM-DBTS increased the content of bioactive factors and had a better performance for the proliferation, migration and tenogenic differentiation of bone marrow-derived stem cells (BMSCs) than DBTS. Furthermore, our results demonstrated that tECM-DBTS promoted tendon regeneration and improved the biomechanical properties of regenerated Achilles tendons in rats by recruiting endogenous stem cells and participating in the functionalization of these stem cells. As a whole, the results of this study demonstrated that the tECM-DBTS can provide a bionic microenvironment for recruiting endogenous stem cells and facilitating in situ regeneration of tendons.
肌腱再生高度依赖于修复微环境中的生物力学和生化信号。在此,我们将脱细胞牛肌腱片(DBTS)与肌腱来源干细胞(TDSCs)的细胞外基质(ECM)相结合,制备了一种具有生物力学和生化功能的支架(tECM-DBTS),为肌腱再生提供一个基于功能性干细胞ECM的微环境。我们之前的研究表明,DBTS在生物力学上适合肌腱修复。在本研究中,对tECM-DBTS的生物学功能进行了体外检测,并通过免疫荧光染色、组织学染色、干细胞追踪、生物力学和功能分析评估了该支架对跟腱修复的效果。结果发现,tECM-DBTS增加了生物活性因子的含量,并且在促进骨髓间充质干细胞(BMSCs)增殖、迁移和向肌腱细胞分化方面比DBTS表现更好。此外,我们的结果表明,tECM-DBTS通过招募内源性干细胞并参与这些干细胞的功能化过程,促进了大鼠跟腱的再生并改善了再生跟腱的生物力学性能。总体而言,本研究结果表明,tECM-DBTS可为招募内源性干细胞和促进肌腱原位再生提供一个仿生微环境。