Human mesenchymal stem/stromal cells (hMSCs) are known to secrete numerous cytokines that signal to endogenous cells and aid in tissue regeneration. However, the role that biomaterial scaffolds can play in controlling hMSC secretory properties has been less explored. Here, microgels were co-assembled with hMSCs using three different microgel populations, with large (190 ± 100 μm), medium (110 ± 60 μm), and small (13 ± 6 μm) diameters, to create distinct porous environments that influenced hMSC clustering. Cells embedded in large diameter microgel networks resided in large clusters (~40 cells), compared to small clusters (~6 cells) observed in networks using medium diameter microgels and primarily single cells in small diameter microgel networks. Using a cytokine microarray, an overall increase in secretion was observed in scaffolds that promoted hMSC clustering, with over 60% of the measured cytokines most elevated in the large diameter microgel networks. N-cadherin interactions were identified as partially mediating these differences, so the microgel formulations were modified with an N-cadherin epitope, HAVDI, to mimic cell-cell interactions. Results revealed increased secretory properties for hMSCs in HAVDI functionalized scaffolds, even the non-clustered cells in small diameter microgel networks. Together, these results demonstrate opportunities for microgel-based scaffold systems for hMSC delivery and tailoring of porous materials properties to promote their secretory potential.

中文翻译：

---

多孔生物点击微凝胶支架控制 hMSC 相互作用并促进其分泌特性。


已知人类间充质干/基质细胞 (hMSC) 会分泌多种细胞因子，向内源性细胞发出信号并帮助组织再生。然而，生物材料支架在控制 hMSC 分泌特性方面所发挥的作用却鲜为人知。在这里，使用三种不同的微凝胶群（大直径（190 ± 100 μm）、中直径（110 ± 60 μm）和小直径（13 ± 6 μm））将微凝胶与 hMSC 共同组装，以创建影响 hMSC 的独特多孔环境聚类。嵌入大直径微凝胶网络中的细胞驻留在大簇（约 40 个细胞）中，而使用中等直径微凝胶网络中观察到的小簇（约 6 个细胞）和小直径微凝胶网络中主要是单细胞。使用细胞因子微阵列，在促进 hMSC 聚集的支架中观察到分泌的总体增加，超过 60% 的测量细胞因子在大直径微凝胶网络中升高最多。 N-钙粘蛋白相互作用被确定为部分介导这些差异，因此用 N-钙粘蛋白表位 HAVDI 修改微凝胶制剂，以模拟细胞与细胞的相互作用。结果显示，HAVDI 功能化支架中 hMSC 的分泌特性增强，甚至小直径微凝胶网络中的非簇状细胞也是如此。总之，这些结果证明了基于微凝胶的支架系统用于 hMSC 递送和定制多孔材料特性以提高其分泌潜力的机会。