The lack of regenerative solutions for demyelination within the central nervous system motivates the development of strategies to expand and drive the bioactivity of the cells, including oligodendrocyte progenitor cells (OPCs), that ultimately give rise to myelination. In this work, we introduce a 3D hyaluronic acid (HA) hydrogel system to study the effects of microenvironmental mechanical properties on the behavior of OPCs. We tuned the stiffness of the hydrogels to match the brain tissue (storage modulus 200–2000 Pa) and studied the effects of stiffness on metabolic activity, proliferation, and cell morphology of OPCs over a 7 day period. Although hydrogel mesh size decreased with increasing stiffness, all hydrogel groups facilitated OPC proliferation and mitochondrial metabolic activity to similar degrees. However, OPCs in the two lower stiffness hydrogel groups (170 ± 42 and 794 ± 203 Pa) supported greater adenosine triphosphate levels per cell than the highest stiffness hydrogels (2179 ± 127 Pa). Lower stiffness hydrogels also supported higher levels of cell viability and larger cell spheroid formation compared to the highest stiffness hydrogels. Together, these data suggest that 3D HA hydrogels are a useful platform for studying OPC behavior and that OPC growth/metabolic health may be favored in lower stiffness microenvironments mimicking brain tissue mechanics.

中文翻译：

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用于建模少突胶质祖细胞行为的3D透明质酸水凝胶，作为基质刚度的函数

中枢神经系统内缺乏脱髓鞘的再生解决方案的缺乏，促使人们发展策略来扩展和驱动细胞（包括少突胶质祖细胞（OPC））的生物活性，最终导致髓鞘化。在这项工作中，我们引入了3D透明质酸（HA）水凝胶系统，以研究微环境机械性能对OPC行为的影响。我们调整了水凝胶的刚度以匹配大脑组织（存储模量为200–2000 Pa），并研究了刚度对7天时间内OPC的代谢活性，增殖和细胞形态的影响。尽管水凝胶的网眼尺寸随着硬度的增加而减小，但是所有水凝胶组都以相似的程度促进了OPC增殖和线粒体代谢活性。然而，两个较低刚度的水凝胶组（170±42和794±203 Pa）中的OPC比最高刚度的水凝胶（2179±127 Pa）支持每个细胞更高的三磷酸腺苷水平。与最高刚度的水凝胶相比，较低刚度的水凝胶还支持更高水平的细胞活力和更大的细胞球体形成。总之，这些数据表明3D HA水凝胶是研究OPC行为的有用平台，在模拟大脑组织力学的较低硬度的微环境中，OPC的生长/代谢健康可能会受到青睐。与最高刚度的水凝胶相比，较低刚度的水凝胶还支持更高水平的细胞活力和更大的细胞球体形成。总之，这些数据表明3D HA水凝胶是研究OPC行为的有用平台，在模拟大脑组织力学的较低硬度的微环境中，OPC的生长/代谢健康可能会受到青睐。与最高刚度的水凝胶相比，较低刚度的水凝胶还支持更高水平的细胞活力和更大的细胞球体形成。总之，这些数据表明3D HA水凝胶是研究OPC行为的有用平台，在模拟大脑组织力学的较低硬度的微环境中，OPC的生长/代谢健康可能会受到青睐。