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首页> 外文期刊>Acta biomaterialia >Cyclic strain anisotropy regulates valvular interstitial cell phenotype and tissue remodeling in three-dimensional culture
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Cyclic strain anisotropy regulates valvular interstitial cell phenotype and tissue remodeling in three-dimensional culture

机译：循环应变各向异性调节三维培养中的瓣膜间质细胞表型和组织重塑

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摘要

Many planar connective tissues exhibit complex anisotropic matrix fiber arrangements that are critical to their biomechanical function. This organized structure is created and modified by resident fibroblasts in response to mechanical forces in their environment. The directionality of applied strain fields changes dramatically during development, aging, and disease, but the specific effect of strain direction on matrix remodeling is less clear. Current mechanobiological inquiry of planar tissues is limited to equibiaxial or uniaxial stretch, which inadequately simulates many in vivo environments. In this study, we implement a novel bioreactor system to demonstrate the unique effect of controlled anisotropic strain on fibroblast behavior in three-dimensional (3-D) engineered tissue environments, using aortic valve interstitial fibroblast cells as a model system. Cell seeded 3-D collagen hydrogels were subjected to cyclic anisotropic strain profiles maintained at constant areal strain magnitude for up to 96 h at 1 Hz. Increasing anisotropy of biaxial strain resulted in increased cellular orientation and collagen fiber alignment along the principal directions of strain and cell orientation was found to precede fiber reorganization. Cellular proliferation and apoptosis were both significantly enhanced under increasing biaxial strain anisotropy (P < 0.05). While cyclic strain reduced both vimentin and alpha-smooth muscle actin compared to unstrained controls, vimentin and alpha-smooth muscle actin expression increased with strain anisotropy and correlated with direction (P < 0.05). Collectively, these results suggest that strain field anisotropy is an independent regulator of fibroblast cell phenotype, turnover, and matrix reorganization, which may inform normal and pathological remodeling in soft tissues.
机译：许多平面结缔组织表现出复杂的各向异性基质纤维排列，这对它们的生物力学功能至关重要。这种组织的结构是由驻留的成纤维细胞根据其周围环境中的机械力创建和修改的。在发育，老化和疾病期间，所施加应变场的方向性发生了巨大变化，但是应变方向对基质重塑的具体影响尚不清楚。当前对平面组织的力学生物学研究仅限于等轴或单轴拉伸，这不能充分模拟许多体内环境。在这项研究中，我们实现了一种新型的生物反应器系统，以主动脉瓣间质成纤维细胞为模型系统，证明了受控各向异性应变对三维（3-D）工程组织环境中成纤维细胞行为的独特影响。细胞接种的3-D胶原水凝胶在1 Hz下经受恒定周期应变幅度下长达96 h的循环各向异性应变曲线。双轴应变的各向异性增加导致细胞取向增加，并且沿应变的主要方向的胶原纤维取向和细胞取向被发现在纤维重组之前。在增加的双轴应变各向异性下，细胞增殖和凋亡均显着增强（P <0.05）。与未应变的对照组相比，周期性应变降低了波形蛋白和平滑肌肌动蛋白的表达，波形蛋白和平滑肌肌动蛋白的表达随应变各向异性而增加，并且与方向相关（P <0.05）。总的来说，这些结果表明，应变场各向异性是成纤维细胞表型，周转率和基质重组的独立调节因子，可能有助于软组织的正常和病理性重构。

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