SHP099-containing multi-targeting hydrogel promotes rapid skin reconstruction through modulating a variety of cells.

Introduction: Adult wound scarring result in functional skin deficits. However, the development of effective measures to modulate the entire wound healing to encourage the skin function reconstruction is still a clinical challenge, as multiple cells are involved in wound healing hierarchically. Hydrogel scaffolds with long-lasting local release provide new insights into the clinical relevance of entire wound healing. Methods: Herein, a multi-targeting hydrogel loaded with SHP099 (Gel-SHP) is designed to modulate multiple cells during wound repair. Results: Our results show that Gel-SHP promotes rapid reconstruction of wound skin by modulating macrophages in the inflammatory stage, fibroblasts in the regeneration stage and smooth muscle cells in the remodelling stage. Gel-SHP could increase M2 macrophage differentiation and remodel the dermal shell of hair follicles through in situ release. Moreover, Gel-SHP may modulate myofibroblasts to promote wound contraction through SHP099-scaffold synergistic interactions. Discussion: Our results provide new insights into the design of functional hydrogels for tissue regeneration applications. Gel-SHP as a promising tool could provide new clues and new research paradigms for future studies and understanding of the wound healing process and dermal shell formation.