Tendon ECM modified bioactive electrospun fibers promote MSC tenogenic differentiation and tendon regeneration
Tendon ECM modified bioactive electrospun fibers promote MSC tenogenic differentiation and tendon regeneration
复制标题
肌腱 ECM 修饰的生物活性静电纺丝促进 MSC 肌腱分化和肌腱再生
DOI：
10.1016/j.apmt.2019.100495
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发表时间：
2020-03-01
影响因子：
8.3
通讯作者：
Liu, Wei
中科院分区：
文献类型：
--
作者：
Tu, Tian;Shen, Yanbing;Liu, Wei
适宜的微生态环境是间充质干细胞向肌腱方向分化和再生的关键因素。在本研究中，可溶性肌腱衍生的细胞外基质（sTECM）被用来修改对齐的静电纺丝纤维与酸中和作用，以创造一个最佳的小生境肌腱再生的环境，其功效进行了评估，使用小鼠MSC肌腱分化在体外和大鼠跟腱再生在体内。结果表明，sTECM修饰的超细纤维具有更好的细胞相容性，能够诱导小鼠MSCs的优势成腱表型，其肌腱标志物包括巩膜轴蛋白、腱调节蛋白、胶原III、莫霍克同源框、核心蛋白聚糖、纤维调节蛋白和双糖链蛋白聚糖的表达增强。相比之下，纯sTECM组分导致小鼠MSC的多谱系分化增强，包括肌腱生成谱系。当在体内施加单侧机械载荷时，这种诱导作用进一步增强。此外，sTECM修饰的支架的植入在体内植入用于原位肌腱再生时创建了包括生物活性sTECM组分、拓扑和机械信号的理想的生态位环境。结果表明，与未修饰的支架相比，sTECM修饰的支架再生的肌腱组织质量更高，组织结构更成熟，组织结构更好，细胞密度和排列更整齐，胶原超微结构更好。定量分析显示，与对照组相比，支架组胶原纤维直径明显增大，力学性能增强，组织分级评分提高，成腱标记物表达水平明显升高（p < 0.05）。这项研究表明，sTECM修饰的pH中性超细纤维可能是一种新的生物活性支架原位肌腱再生，值得进一步研究在大型动物。(C)2019爱思唯尔有限公司版权所有。
Proper niche environment is the key factor for mesenchymal stem cells (MSCs) involved tendon-lineage differentiation and regeneration. In the present study, soluble tendon derived extracellular matrix (sTECM) was used to modify aligned electrospun fibers with acid neutralizing effect in order to create an optimal niche environment for tendon regeneration, and its efficacy was evaluated using mouse MSC tenogenic differentiation in vitro and rat Achilles tendon regeneration in vivo. The results showed that sTECM modified ultrafine fibers were more cytocompatible and capable of inducing a predominant tenogenic phenotype of mouse MSCs with the enhanced expression of tendon markers including scleraxis, tenomodulin, collagen III, mohawk homeobox, decorin, fibromodulin and biglycan. By contrast, pure sTECM components led to enhanced multi-lineage differentiation of mouse MSCs including tenogenic lineage. This inductive effect was further enhanced when unilateral mechanical loading was applied in vivo. Moreover, the implantation of sTECM modified scaffold created an ideal niche environment including bioactive sTECM components, topological and mechanical signals, upon in vivo implantation for in situ tendon regeneration. As the results, sTECM modified scaffold in comparison with the non-modified one regenerated higher quality tendon tissue with the features of more mature tissue structure, better tissue organization, cell density and alignment as well as better collagen ultrastructure. Quantitative analysis demonstrated significantly bigger collagen fibril diameter, stronger mechanical property and better tissue grading score and higher expression levels of tenogenic markers when compared to those of control scaffold (p < 0.05). This study demonstrated that sTECM modified pH-neutral ultrafine fibers may represent a novel bioactive scaffold for in situ tendon regeneration, which deserves further investigation in large animals. (C) 2019 Elsevier Ltd. All rights reserved.