Olsen Sara J, Leader Rose E, Mortimer Abigail L, Almeida Bethany
Department of Chemical and Biomolecular Engineering, Clarkson University, Potsdam, NY 13699, USA.
Department of Mechanical and Aerospace Engineering, Clarkson University, Potsdam, NY 13699, USA.
Mechanobiol Med. 2024 Dec 8;3(1):100111. doi: 10.1016/j.mbm.2024.100111. eCollection 2025 Mar.
Human mesenchymal stem cells (hMSCs) have immense wound healing potential due to their immunomodulatory behavior. To control this behavior and reduce heterogeneity, researchers look to biomaterials, as matrix stiffness and viscoelasticity have been shown to control hMSC immunomodulation. However, the understanding of the effects of these biophysical cues on hMSC immunomodulation remains limited; a broad study investigating the potentially synergistic effects of matrix stiffness and viscoelasticity on hMSC immunomodulation is needed in order to support future work developing biomaterials for hMSC wound healing applications. We developed polyacrylamide (PAAm) gels with varying matrix stiffnesses with or without a viscoelastic element and explored the effects of these on hMSC-matrix interactions and immunomodulatory cytokine expression in both a normal growth media and an immunomodulatory growth media mimetic of a chronic, non-healing wound. Expression of IL-10, VEGF, and PGE were upregulated in immunomodulatory growth media over normal growth media, demonstrating the synergistic effects of biochemical signaling on hMSC immunomodulatory behavior. In addition, the addition of a viscoelastic element had both inhibitory and accentuating effects based on the cytokine and biochemical signaling in the cell culture media. Overall, this study provides a broad perspective on the immunomodulatory behavior of hMSCs due to stiffness and viscoelasticity.
人间充质干细胞（hMSCs）因其免疫调节行为而具有巨大的伤口愈合潜力。为了控制这种行为并减少异质性，研究人员将目光投向生物材料，因为已证明基质硬度和粘弹性可控制hMSC的免疫调节。然而，对这些生物物理线索对hMSC免疫调节影响的理解仍然有限；需要进行一项广泛的研究，调查基质硬度和粘弹性对hMSC免疫调节的潜在协同作用，以支持未来开发用于hMSC伤口愈合应用的生物材料的工作。我们制备了具有不同基质硬度且有或没有粘弹性元件的聚丙烯酰胺（PAAm）凝胶，并在正常生长培养基和模拟慢性不愈合伤口的免疫调节生长培养基中，探究了它们对hMSC-基质相互作用和免疫调节细胞因子表达的影响。与正常生长培养基相比，免疫调节生长培养基中IL-10、VEGF和PGE的表达上调，证明了生化信号对hMSC免疫调节行为的协同作用。此外，根据细胞培养基中的细胞因子和生化信号，添加粘弹性元件具有抑制和增强作用。总体而言，本研究提供了关于硬度和粘弹性对hMSCs免疫调节行为影响的广泛观点。
