Microskin‐Inspired Injectable MSC‐Laden Hydrogels for Scarless Wound Healing with Hair Follicles

• Published in: Advanced healthcare materials 2020-05, Vol.9 (10), p.e2000041-n/a
• Main Authors: Zheng, Xin, Ding, Zhaozhao, Cheng, Weinan, Lu, Qiang, Kong, Xiangdong, Zhou, Xiaozhong, Lu, Guozhong, Kaplan, David L.
• Format: Article
• Language: English
• Subjects: Angiogenesis; Biocompatible Materials; Biomaterials; Biomedical materials; Defects; Follicles; Hair; Hair Follicle; Hydrogels; In vivo methods and tests; injectable hydrogels; Macrophages; Mesenchymal Stem Cells; Mesenchyme; Microgels; Nanofibers; Paracrine signalling; Phenotypes; Recovery of function; Regeneration; scarless skin regeneration; Scars; Silk; Skin; Stem cells; Wound Healing
• ISSN: 2192-2640; 2192-2659
• DOI: 10.1002/adhm.202000041

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. Microgels composed of aligned silk nanofibers are used to load mesenchymal stem cells (MSCs) to actively modulate the paracrine. The MSCs‐laden microgels are blended with injectable silk nanofiber hydrogels to accelerate the wound healing. The synergistic action of MSCs‐laden hydrogel systems stimulates angiogenesis and M1‐M2 phenotype switching of macrophages, achieving scarless skin regeneration with hair follicles.