Scarless skin regeneration with functional tissue remains a challenge for full-thickness wounds. Here, mesenchymal stem cell (MSC)-laden hydrogels are developed for scarless wound healing with hair follicles. Microgels composed of aligned silk nanofibers are used to load MSCs to modulate the paracrine. MSC-laden microgels are dispersed into injectable silk nanofiber hydrogels, forming composites biomaterials containing the cells. The injectable hydrogels protect and stabilize the MSCs in the wounds. The synergistic action of silk-based composite hydrogels and MSCs stimulated angiogenesis and M1-M2 phenotype switching of macrophages, provides a suitable niche for functional recovery of wounds. Compared to skin defects treated with MSC-free hydrogels, the defects treated with the MSC-laden composite hydrogels heal faster and form scarless tissues with hair follicles. Wound healing can be further improved by adjusting the ratio of silk nanofibers and particles and the loaded MSCs, suggesting tunability of the system. To the best of current knowledge, this is the first time scarless skin regeneration with hair follicles based on silk material systems is reported. The improved wound healing capacity of the systems suggests future in vivo studies to compare to other biomaterial systems related to clinical goals in skin regeneration in the absence of scarring.

中文翻译：

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受 Microskin 启发的可注射 MSC 负载水凝胶，用于毛囊无疤痕伤口愈合。

具有功能组织的无疤痕皮肤再生对于全层伤口来说仍然是一个挑战。在这里，我们开发了充满间充质干细胞（MSC）的水凝胶，用于毛囊伤口的无疤痕愈合。由排列整齐的丝纳米纤维组成的微凝胶用于加载间充质干细胞以调节旁分泌。将含有 MSC 的微凝胶分散到可注射的丝纳米纤维水凝胶中，形成含有细胞的复合生物材料。可注射的水凝胶可以保护和稳定伤口中的间充质干细胞。丝基复合水凝胶和间充质干细胞的协同作用刺激了巨噬细胞的血管生成和M1-M2表型转换，为伤口的功能恢复提供了合适的环境。与用不含 MSC 的水凝胶治疗的皮肤缺损相比，用含有 MSC 的复合水凝胶治疗的皮肤缺损愈合得更快，并形成带有毛囊的无疤组织。通过调整丝纳米纤维和颗粒以及加载的 MSC 的比例可以进一步改善伤口愈合，这表明系统的可调性。据目前所知，这是首次报道基于丝材料系统的毛囊无疤痕皮肤再生。该系统改善的伤口愈合能力表明，未来的体内研究可以与其他生物材料系统进行比较，以实现无疤痕皮肤再生的临床目标。