Department of Orthopedic Surgery, the Second Affiliated Hospital, Zhejiang University, School of Medicine, Hangzhou, 310009, China.
J Mater Chem B. 2019 Apr 7;7(13):2201-2211. doi: 10.1039/c8tb02759e. Epub 2019 Feb 27.
Tendon injuries are common and require a long time to heal, and are particularly associated with some adverse problems such as adhesion and rupture. Herein, we aim to develop new bioactive scaffolds endowed with stem cell sheets and growth factors to enable cell migration and proliferation favorable for tendon regeneration in situ. An exogenous basic fibroblast growth factor (bFGF)-loaded fibrin gel was firstly incorporated into the porous network of knitted poly(lactide-co-glycolide) (PLGA) scaffolds and then sheets of mesenchymal stem cells (MSCs) were also integrated into the scaffolds. It was shown that the pores in the knitted PLGA scaffold were readily filled with a complex network of fibrin fiber gel and the fibrin fibers were beneficial for the controlled release of bFGF over a long time period. After transplantation in a critical-size Achilles tendon defect model (7 mm) in the rat right hindlimb, gross observation revealed no immunologic incompatibility or rejection derived from the scaffold systems. It was observed that the MSC sheets contributed directly to tendon regeneration, and exerted an environment-modifying effect on the injuries in situ, consistent with the beneficial effect of bFGF. It was interesting that the knitted PLGA-fibrin gel scaffolds loaded with MSC sheets and bFGF showed the highest expression of tendon-related gene markers and outstanding repair efficacy, including appreciable biomechanical strength and native-like histological microstructures. Therefore, the integration of MSC sheets and bFGF into PLGA/bFGF-fibrin gel scaffolds may stimulate the proliferation and tenogenic differentiation of MSCs in situ and synergistically enhance the injured tendon reconstruction.
肌腱损伤很常见,需要很长时间才能愈合,并且特别与一些不良问题有关,例如粘连和破裂。在此,我们旨在开发具有干细胞片和生长因子的新型生物活性支架,以促进细胞迁移和增殖,有利于原位肌腱再生。首先将外源碱性成纤维细胞生长因子(bFGF)负载的纤维蛋白凝胶掺入到编织的聚(乳酸-共-乙醇酸)(PLGA)支架的多孔网络中,然后将间充质干细胞(MSCs)片也整合到支架中。结果表明,编织的 PLGA 支架中的孔很容易被纤维蛋白凝胶的复杂网络填充,并且纤维蛋白纤维有利于 bFGF 的长时间控制释放。在大鼠右后肢的跟腱大缺损模型(7mm)中进行移植后,肉眼观察未发现支架系统产生免疫不相容或排斥反应。观察到 MSC 片直接有助于肌腱再生,并对原位损伤产生环境修饰作用,与 bFGF 的有益作用一致。有趣的是,负载 MSC 片和 bFGF 的编织 PLGA-纤维蛋白凝胶支架表现出最高的肌腱相关基因标志物表达和出色的修复效果,包括可观的生物力学强度和类似天然的组织学微观结构。因此,将 MSC 片和 bFGF 整合到 PLGA/bFGF-纤维蛋白凝胶支架中可能会刺激原位 MSC 的增殖和肌腱分化,并协同增强受损肌腱的重建。
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