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Title:: The effect of square mechanical constraints on the inhomogeneous microtissue

作者:: 窦婷1; 2; 3; 邓林红1; 2; 3△; 王翔1; 2; 3△; （1.常州大学生物医学工程与健康科学研究院，常州 213164；2.常州大学药学院，常州 213164;3.常州大学生物与食品工程学院，常州 213164）

Author(s):: DOU Ting1; 2; 3; DENG Linhong1; 2; 3; WANG Xiang1; 2; 3; （1.Institute of Biomedical Engineering and Health Sciences, Changzhou University, Changzhou 213164, China；2.School of Pharmacy, Changzhou University, Changzhou 213164；3. School of Biological and Food Engineering，Changzhou University, Changzhou 213164）

Keywords:: Mechanical boundary; 3D microtissue; Fibroblast; Extracellular matrix; Fiber arrangement; Cell proliferation; Macromolecular diffusion

摘要:: 为探究组织力学微环境，尤其是力学约束产生的张力如何影响细胞外基质非均一结构的形成，本研究制备了一种正方形聚二甲基硅氧烷（polydimethylsiloxane ，PDMS）微弦，并将由成纤维细胞和胶原构成的微组织培养在微弦上。研究表明，微组织在微弦直角区域受到的力学约束高于中央区域。通过对不同力学约束区域中细胞和细胞外基质进行表征和对比发现，高力学约束内的细胞呈各向同性分布，并表达出更高水平的纤连蛋白，导致其硬度增大，证明正方形力学约束可诱导非均一致密微组织的形成。此外，4 kDa葡聚糖在高力学约束区域的扩散速度明显低于低力学约束区域，该结果将有助于进一步了解大分子药物在组织内部的传递。

Abstract:: In order to explore the microenvironment of tissue mechanics, especially how the tension caused by mechanical constraints affecting the inhomogeneous structures formation in the extracellular matrix, we prepared a square polydimethylsiloxane (PDMS) microstring and cultured microtissues composed of fibroblasts and collagen on the microstring. The results showed that the mechanical constraint in the right-angle region of the microstring was higher than that in the central region. By charactering and comparing cells and extracellular matrix in regions of different mechanical constraints, it was found that the cells in high mechanical constraints region showed isotropic distribution and expressed a higher level of fibronectin, resulting in increased stiffness. It suggested that square mechanical constraints could induce the formation of heterogeneous dense tissue. In addition, the diffusion rate of 4 kDa dextran in the high mechanical constraint region was significantly lower than that in the low mechanical constraint region. The results will help further understand the delivery of macromolecular drugs in tissue.