Integration of mesenchymal stem cell sheet and bFGF-loaded fibrin gel in knitted PLGA scaffolds favorable for tendon repair
Integration of mesenchymal stem cell sheet and bFGF-loaded fibrin gel in knitted PLGA scaffolds favorable for tendon repair
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将间充质干细胞片和负载 bFGF 的纤维蛋白凝胶整合到有利于肌腱修复的针织 PLGA 支架中
DOI：
10.1039/c8tb02759e
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发表时间：
2019-04-07
影响因子：
7
通讯作者：
Xu, Kan
中科院分区：
文献类型：
--
作者：
Zhao, Tengfei;Qi, Yiying;Xu, Kan
肌腱损伤是常见的，需要很长时间才能愈合，特别是与一些不良问题，如粘连和断裂有关。在此，我们的目标是开发新的具有生物活性的支架，赋予干细胞片和生长因子，使细胞迁移和增殖有利于肌腱原位再生。首先将外源性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聚乳酸-羟基乙酸酯（PLGA）支架的多孔网络中，然后将间充质干细胞（MSCs）片掺入支架中。结果表明，编织PLGA支架的孔隙容易被复杂的纤维蛋白纤维凝胶网络填充，纤维蛋白纤维有利于bFGF的长时间控释。在大鼠右后肢的临界尺寸跟腱缺损模型（7mm）中移植后，粗略观察显示支架系统没有免疫不相容性或排斥反应。我们观察到间充质干细胞片直接促进肌腱再生，并对原位损伤具有环境修饰作用，这与bFGF的有益作用一致。有趣的是，装载MSC片和bFGF的针织plga -纤维蛋白凝胶支架显示出最高的肌腱相关基因标记表达和出色的修复效果，包括明显的生物力学强度和天然样的组织学微观结构。因此，将MSC片和bFGF整合到PLGA/bFGF-纤维蛋白凝胶支架中可以刺激MSCs原位增殖和成肌腱分化，协同促进损伤肌腱重建。
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.