Polymer fiber-based models of connective tissue repair and healing.
Polymer fiber-based models of connective tissue repair and healing.
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DOI：
10.1016/j.biomaterials.2016.10.013
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发表时间：
2017-01
期刊：
影响因子：
14
通讯作者：
Lu HH
中科院分区：
文献类型：
--
作者：
Lee NM;Erisken C;Iskratsch T;Sheetz M;Levine WN;Lu HH
伤口愈合的生理相关模型对于理解结缔组织修复和愈合的生物学至关重要。它们还可用于识别软组织移植物设计所必需的关键细胞过程和基质特征。对肌腱损伤后修复的各个阶段进行建模，生产了不同纤维直径（nano-1 (390 nm) < nano-2 (740 nm) < micro (1420 nm)）的聚合物网。 Nano-2 组中还引入了对齐来模拟正在经历生物愈合而不是疤痕形成的基质。随着时间的推移，人类肌腱成纤维细胞对这些模型基底的反应被评估为纤维直径和排列的函数。据观察，未排列的纳米级纤维的修复模型增强了细胞生长和胶原蛋白合成，而在由未排列的微米级纤维组成的成熟修复模型中，这些结果显着降低。与纳米纤维相比，未对齐网格上的桩蛋白和肌动蛋白的组织在微米纤维上得到增强，而 RhoA 和 Rac1 在纳米纤维上的表达和活性更高。相比之下，排列整齐的纳米纤维促进了早期细胞组织，同时从长远来看减少了过度的细胞生长和胶原蛋白的产生。这些结果表明，未排列的纳米级纤维的早期修复模型引发了伤口修复增殖期的响应特征，而由未排列的微米级纤维组成的更成熟的模型更能代表重塑阶段，支持细胞组织，同时抑制生长和生物合成。有趣的是，在纳米纤维模型中引入纤维排列改变了成纤维细胞从修复到愈合的反应，这表明基质排列是避免疤痕形成和促进软组织损伤生物愈合的关键设计因素。
Physiologically relevant models of wound healing are essential for understanding the biology of connective tissue repair and healing. They can also be used to identify key cellular processes and matrix characteristics essential for the design of soft tissue grafts. Modeling the various stages of repair post tendon injury, polymer meshes of varying fiber diameter (nano-1 (390 nm) < nano-2 (740 nm) < micro (1420 nm)) were produced. Alignment was also introduced in the nano-2 group to model matrix undergoing biological healing rather than scar formation. The response of human tendon fibroblasts on these model substrates were evaluated over time as a function of fiber diameter and alignment. It was observed that the repair models of unaligned nanoscale fibers enhanced cell growth and collagen synthesis, while these outcomes were significantly reduced in the mature repair model consisting of unaligned micron-sized fibers. Organization of paxillin and actin on unaligned meshes was enhanced on micro-compared to nano-sized fibers, while the expression and activity of RhoA and Rac1 were greater on nanofibers. In contrast, aligned nanofibers promoted early cell organization, while reducing excessive cell growth and collagen production in the long term. These results show that the early-stage repair model of unaligned nanoscale fibers elicits a response characteristic of the proliferative phase of wound repair, while the more mature model consisting of unaligned micron-sized fibers is more representative of the remodeling phase by supporting cell organization while suppressing growth and biosynthesis. Interestingly, introduction of fiber alignment in the nanofiber model alters fibroblast response from repair to healing, implicating matrix alignment as a critical design factor for circumventing scar formation and promoting biological healing of soft tissue injuries.
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