Surface-directed engineering of tissue anisotropy in microphysiological models of musculoskeletal tissue.

Surface-directed engineering of tissue anisotropy in microphysiological models of musculoskeletal tissue.
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肌肉骨骼组织微生理模型中组织各向异性的表面定向工程。

DOI:
10.1126/sciadv.abe9446
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发表时间:
2021-03
期刊:
影响因子:
13.6
通讯作者:
Huh D
Huh D
中科院分区:
综合性期刊1区
文献类型:
--
作者:
Mondrinos MJ;Alisafaei F;Yi AY;Ahmadzadeh H;Lee I;Blundell C;Seo J;Osborn M;Jeon TJ;Kim SM;Shenoy VB;Huh D

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一种发育启发的组织工程方法,使微生理肌肉骨骼组织模型的建设。在这里,我们提出了一种方法来模拟和适应机械调节形态发生,使用收缩细胞作为雕塑家的工程组织各向异性在体外。我们的方法使用异双功能交联剂来产生机械边界约束,其引导载有细胞的细胞外基质水凝胶构建体的表面定向雕刻。使用这种方法,我们设计了具有结构和机械各向异性的线性对齐组织。一个多尺度的硅模型的雕刻过程中,揭示了细胞收缩性增加的功能,在各向异性组织中的主应力极化。我们还表明,线性排列的组织的各向异性生物物理微环境增强可溶性因子介导的间充质干细胞的肌腱和肌分化。我们的方法的应用证明了(i)骨骼肌阵列筛选急性氧化损伤的治疗性调节剂和(ii)肺癌恶病质的3D微生理模型研究肿瘤源性信号诱导的炎症和氧化性肌肉损伤。
A developmentally inspired tissue engineering method enables the construction of microphysiological musculoskeletal tissue models. Here, we present an approach to model and adapt the mechanical regulation of morphogenesis that uses contractile cells as sculptors of engineered tissue anisotropy in vitro. Our method uses heterobifunctional cross-linkers to create mechanical boundary constraints that guide surface-directed sculpting of cell-laden extracellular matrix hydrogel constructs. Using this approach, we engineered linearly aligned tissues with structural and mechanical anisotropy. A multiscale in silico model of the sculpting process was developed to reveal that cell contractility increases as a function of principal stress polarization in anisotropic tissues. We also show that the anisotropic biophysical microenvironment of linearly aligned tissues potentiates soluble factor-mediated tenogenic and myogenic differentiation of mesenchymal stem cells. The application of our method is demonstrated by (i) skeletal muscle arrays to screen therapeutic modulators of acute oxidative injury and (ii) a 3D microphysiological model of lung cancer cachexia to study inflammatory and oxidative muscle injury induced by tumor-derived signals.
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