There is a desire in regenerative medicine to create biofunctional materials that can control and direct cell function in a precise manner. One particular stem cell of interest, human mesenchymal stem cells (hMSCs), can function as regulators of the immunogenic response and aid in tissue regeneration and wound repair. Here, a porous hydrogel scaffold assembled from microgel subunits was used to recapitulate part of this immunomodulatory behavior. The scaffolds were used to culture a macrophage cell line, while cytokines were delivered exogenously to polarize the macrophages to either a pro‐inflammatory (M1) or alternatively activated (M2a) phenotypes. Using a cytokine array, interleukin 10 (IL‐10) was identified as one key anti‐inflammatory factor secreted by hMSCs in pro‐inflammatory conditions; it was elevated (125 ± 25 pg/ml) in pro‐inflammatory conditions compared to standard medium (6 ± 10 pg/ml). The ability of hMSC laden scaffolds to reverse the M1 phenotype was then examined, even in the presence of exogenous pro‐inflammatory cytokines. Co‐culture of M1 and M2 macrophages with hMSCs reduced the secretion of TNFα, a pro‐inflammatory cytokine even in the presence of pro‐inflammatory stimulatory factors. Next, IL‐10 was supplemented in the medium or tethered directly to the microgel subunits; both methods limited the secretion of pro‐inflammatory cytokines of encapsulated macrophages even in pro‐inflammatory conditions. Cumulatively, these results reveal the potential of biofunctional microgel‐based scaffolds as acellular therapies to present anti‐inflammatory cytokines and control the immunogenic cascade.

中文翻译：

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间充质干细胞启发的微凝胶支架控制巨噬细胞极化

再生医学希望创造能够以精确方式控制和指导细胞功能的生物功能材料。一种特殊的感兴趣的干细胞，人类间充质干细胞 (hMSCs)，可以作为免疫原性反应的调节剂，并有助于组织再生和伤口修复。在这里，由微凝胶亚基组装而成的多孔水凝胶支架被用来概括这种免疫调节行为的一部分。支架用于培养巨噬细胞系，而细胞因子被外源传递以将巨噬细胞极化为促炎 (M1) 或替代激活 (M2a) 表型。使用细胞因子阵列，白细胞介素 10 (IL-10) 被确定为 hMSC 在促炎条件下分泌的一种关键抗炎因子；与标准培养基 (6 ± 10 pg/ml) 相比，它在促炎条件下升高 (125 ± 25 pg/ml)。然后检测了载有 hMSC 的支架逆转 M1 表型的能力，即使在存在外源性促炎细胞因子的情况下也是如此。M1 和 M2 巨噬细胞与 hMSCs 的共培养减少了 TNFα 的分泌，TNFα 是一种促炎细胞因子，即使在促炎刺激因子存在的情况下也是如此。接下来，在培养基中补充 IL-10 或直接连接到微凝胶亚基上；这两种方法都限制了被包裹的巨噬细胞的促炎细胞因子的分泌，即使在促炎条件下也是如此。总的来说，这些结果揭示了基于生物功能微凝胶的支架作为非细胞疗法的潜力，可呈现抗炎细胞因子并控制免疫原性级联反应。