Helical nanofiber yarn enabling highly stretchable engineered microtissue
Helical nanofiber yarn enabling highly stretchable engineered microtissue
复制标题
螺旋纳米纤维纱线可实现高度可拉伸的工程微组织
DOI：
10.1073/pnas.1821617116
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发表时间：
2019-05-07
影响因子：
11.1
通讯作者：
Guo, Ming
中科院分区：
文献类型：
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作者：
Li, Yiwei;Guo, Fengyun;Guo, Ming
意义制造可拉伸和坚韧的重组组织的挑战在于当前方法的局限性，即在保持细胞功能的同时再现天然组织的特殊机械性能。在这里，我们通过整合静电纺丝和组织工程来模拟原生机械复杂性，以开发由生物启发的分层螺旋支架和种子细胞组成的高度可拉伸的活组织。组织结构良好的组织结构具有57 GJ m−3的韧性，并且由于非仿射纤维变形，可以拉伸至其长度的15倍，同时保护细胞免受严重的循环应变（600%）。通过利用机械概念设计的这种分层微组织具有促进肌生成的额外能力，可用于组织工程、再生医学和人工生命系统中的应用。开发具有模仿天然可拉伸组织（如肌肉和肌腱）的机械性能的微组织对于组织工程和再生医学具有很高的需求。然而，尽管合成生物材料取得了重大进展，但制造具有高拉伸性的活微组织仍然具有挑战性，因为对微组织施加大的应变可能会通过破坏其结构来损伤细胞。受天然纤维组织的分层螺旋结构及其非仿射变形行为的启发，我们开发了一种由分层螺旋纱线支架组成的高度可拉伸且坚韧的微组织纤维，其尺寸从纳米到毫米不等，可以克服这一限制。这种微组织可以拉伸到其初始长度的15倍，韧性为57 GJ m−3。更重要的是，在这种支架上生长的细胞保持高活力，即使在严重的循环应变（高达600%）下，这可能是由于在大应变下的非仿射变形，模仿天然生物聚合物支架。此外，作为原理的证明，我们证明了螺旋状螺旋纱线的纳米形貌能够诱导细胞骨架排列和核伸长，这通过触发具有PDZ结合基序（TAZ）的转录辅激活因子的核转位来促进间充质干细胞的肌源性分化。我们在这里开发的高度可拉伸的微组织将促进各种组织工程应用和工程生命系统的发展。
Significance The challenge in manufacturing stretchable and tough reconstituted tissues lies in the limitation of current approaches to recapitulate the exceptional mechanical properties of native tissues while maintaining cellular functions. Here, we simulate native mechanical complexity by integrating electrospinning and tissue engineering to develop a highly stretchable living tissue consisting of bioinspired hierarchical helical scaffold and seeded cells. The well-organized tissue construct has a toughness of 57 GJ m−3 and can be stretched up to 15 times its length while sheltering cells from severe cyclic strains (600%), owing to nonaffine fiber deformation. With the additional ability to promote myogenesis, this hierarchical microtissue designed by leveraging mechanical concepts may be used for applications in tissue engineering, regenerative medicine, and artificial living systems. Development of microtissues that possess mechanical properties mimicking those of native stretchable tissues, such as muscle and tendon, is in high demand for tissue engineering and regenerative medicine. However, regardless of the significant advances in synthetic biomaterials, it remains challenging to fabricate living microtissue with high stretchability because application of large strains to microtissues can damage the cells by rupturing their structures. Inspired by the hierarchical helical structure of native fibrous tissues and its behavior of nonaffine deformation, we develop a highly stretchable and tough microtissue fiber made up of a hierarchical helix yarn scaffold, scaling from nanometers to millimeters, that can overcome this limitation. This microtissue can be stretched up to 15 times its initial length and has a toughness of 57 GJ m−3. More importantly, cells grown on this scaffold maintain high viability, even under severe cyclic strains (up to 600%) that can be attributed to the nonaffine deformation under large strains, mimicking native biopolymer scaffolds. Furthermore, as proof of principle, we demonstrate that the nanotopography of the helical nanofiber yarn is able to induce cytoskeletal alignment and nuclear elongation, which promote myogenic differentiation of mesenchymal stem cells by triggering nuclear translocation of transcriptional coactivator with PDZ-binding motif (TAZ). The highly stretchable microtissues we develop here will facilitate a variety of tissue engineering applications and the development of engineered living systems.