Bose Prasenjit, Eyckmans Jeroen, Nguyen Thao D, Chen Christopher S, Reich Daniel H
Department of Physics and Astronomy, Johns Hopkins University, Baltimore, Maryland 21218, United States.
Department of Biomedical Engineering and the Biological Design Center, Boston University, Boston, Massachusetts 02215, United States.
ACS Biomater Sci Eng. 2019 Aug 12;5(8):3843-3855. doi: 10.1021/acsbiomaterials.8b01183. Epub 2018 Dec 20.
The structure and stiffness of the extracellular matrix (ECM) in living tissues play a significant role in facilitating cellular functions and maintaining tissue homeostasis. However, the wide variation and complexity in tissue composition across different tissue types make comparative study of the impact of matrix architecture and alignment on tissue mechanics difficult. Here we present a microtissue-based system capable of controlling the degree of ECM alignment in 3D self-assembled fibroblast-populated collagen matrix, anchored around multiple elastic micropillars. The pillars provide structural constraints, control matrix alignment, enable measurement of the microtissues' contractile forces, and provide the ability to apply tensile strain using magnetic particles. Utilizing finite element models (FEMs) to parametrize results of mechanical measurements, spatial variations in the microtissues' Young's moduli across different regions were shown to be correlated with the degree of ECM fiber alignment. The aligned regions were up to six times stiffer than the unaligned regions. The results were not affected by suppression of cellular contractile forces in matured microtissues. However, comparison to a distributed fiber anisotropic model shows that variations in fiber alignment alone cannot account for the variations in the observed moduli, indicating that fiber density and tissue geometry also play important roles in the microtissues' properties. These results suggest a complex interplay between mechanical boundary constraints, ECM alignment, density, and mechanics and offer an approach combining engineered microtissues and computational modeling to elucidate these relationships.
活组织中细胞外基质（ECM）的结构和刚度在促进细胞功能和维持组织稳态方面发挥着重要作用。然而，不同组织类型的组织组成存在广泛差异和复杂性，这使得比较基质结构和排列对组织力学的影响变得困难。在此，我们展示了一种基于微组织的系统，该系统能够控制三维自组装成纤维细胞填充胶原基质中ECM的排列程度，该基质围绕多个弹性微柱锚定。这些柱子提供结构约束，控制基质排列，能够测量微组织的收缩力，并具备使用磁性颗粒施加拉伸应变的能力。利用有限元模型（FEM）对力学测量结果进行参数化，结果表明微组织不同区域的杨氏模量空间变化与ECM纤维排列程度相关。排列区域的刚度比未排列区域高多达六倍。成熟微组织中细胞收缩力的抑制并未影响结果。然而，与分布式纤维各向异性模型的比较表明，仅纤维排列的变化无法解释观察到的模量变化，这表明纤维密度和组织几何形状在微组织特性中也起着重要作用。这些结果表明，机械边界约束、ECM排列、密度和力学之间存在复杂的相互作用，并提供了一种结合工程化微组织和计算建模来阐明这些关系的方法。
