Papillary fibroblast-recruiting injectable self-healing multifunctional hydrogels for wound regeneration

The recruitment of key cells to regeneration sites is a promising strategy to promote functional wound healing. Dermal fibroblasts exhibit a heterogeneous population of cells during homeostasis and in response to injury. Papillary fibroblasts play central regulatory roles in the regeneration of skin appendages during wound healing. Inspired by the phenomenon where bait for grass carp can attract grouped grass carps to a fishing spot soon, “Grass Carp Fishing” multifunctional hydrogels, that is, codelivery of an antibody of leucine-rich repeats and immunoglobulin-like domains 1 (Lrig1) on the surface of papillary fibroblasts and insulin-like growth factor 1 (IGF1) with recruitment function, can recruit papillary fibroblasts. In the experiments, carboxymethyl chitosan showed positive effects in promoting cell proliferation and neovascularization, while dopamine-grafted gelatin was effective in stabilizing the structure and prolonging the degradation time. The sustained release of Lrig1 antibodies and IGF1 from injectable self-healing multifunctional hydrogels persistently accelerated the migration and proliferation of Lrig1⁺ fibroblasts. The in vivo results from a full-thickness cutaneous wound model showed that injectable self-healing multifunctional hydrogel accelerated wound healing and skin regeneration through the recruitment of Lrig1⁺ papillary fibroblasts in wound tissue. Our findings reveal an injectable self-healing multifunctional hydrogel for regeneration, a promising approach to promoting skin wound healing.