Department of Chemical Engineering, University of Virginia, Charlottesville, Virginia 22903, United States.
Department of Biomedical Engineering, University of Virginia, Charlottesville, Virginia 22903, United States.
Biomacromolecules. 2020 Dec 14;21(12):4962-4971. doi: 10.1021/acs.biomac.0c01164. Epub 2020 Oct 28.
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.
中枢神经系统脱髓鞘缺乏再生解决方案，这促使人们开发策略来扩增和驱动细胞的生物活性，包括少突胶质前体细胞（OPC），这些细胞最终产生髓鞘。在这项工作中，我们引入了一种 3D 透明质酸（HA）水凝胶系统来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脑组织（储能模量 200-2000 Pa），并研究了刚度对 OPC 代谢活性、增殖和细胞形态的影响，时间为 7 天。尽管水凝胶的网格尺寸随刚度的增加而减小，但所有水凝胶组都能促进 OPC 的增殖和线粒体代谢活性，程度相似。然而，在两个较低刚度水凝胶组（170±42 和 794±203 Pa）中，OPC 的细胞内三磷酸腺苷（ATP）水平高于最高刚度水凝胶组（2179±127 Pa）。与最高刚度水凝胶相比，较低刚度水凝胶还支持更高的细胞活力水平和更大的细胞球体形成。这些数据表明，3D HA 水凝胶是研究 OPC 行为的有用平台，并且 OPC 的生长/代谢健康可能在模拟脑组织力学的较低刚度微环境中得到促进。
