Department of Mechanical Engineering, Massachusetts Institute of Technology, Cambridge, MA 02139.
Key Laboratory of Bioinspired Smart Interfacial Science and Technology of Ministry of Education, Beijing Advanced Innovation Center for Biomedical Engineering, School of Chemistry, Beihang University, Beijing 100191, P. R. China.
Proc Natl Acad Sci U S A. 2019 May 7;116(19):9245-9250. doi: 10.1073/pnas.1821617116. Epub 2019 Apr 24.
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 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.
开发出机械性能类似于天然可拉伸组织（如肌肉和肌腱）的微组织对于组织工程和再生医学非常重要。然而，尽管在合成生物材料方面取得了重大进展，但制造具有高拉伸性的活体微组织仍然具有挑战性，因为将大应变应用于微组织会破坏细胞结构而导致细胞破裂。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和坚韧的微组织纤维，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初始长度的 15 倍，韧性为 57 GJ m。更重要的是，即使在高达 600%的严重循环应变下（这归因于大应变下的非仿射变形，模拟天然生物聚合物支架），生长在该支架上的细胞仍保持高活力。此外，作为原理验证，我们证明了螺旋纳米纤维纱线的纳米形貌能够诱导细胞骨架的排列和核的伸长，通过触发转录共激活因子 TAZ 的核易位来促进间充质干细胞的成肌分化。我们在这里开发的高可拉伸微组织将促进各种组织工程应用和工程化活体系统的发展。
