Electrical and immune stimulation-based hydrogels synergistically realize scarless wound healing via amplifying endogenous electrophysiological function and promoting Macrophage Phenotype-Switching.

[Display omitted] • Electrical and immune stimulation-based hydrogels sHA/G-GM synergistically realize scarless wound healing. • sHA/G-GM modulate fibroblast activation via amplifying the endogenous electrophysiology. • sHA/G-GM modulate immune microenvironment via promoting macrophage phenotype-switching. Scars are a consequence of the wound healing process, and scarless wound healing remains a substantial clinical challenge. In this study, conductive hydrogels (named sHA/G-GM) were developed to synergistically realize scarless wound healing through electrical and immune stimulation. sHA/G-GM was prepared as high-sulfated hyaluronan (sHA) modified graphene (sHA/G) homodispersing in gelatin methacrylate, and sHA/G was released and absorbed by cytomembranes. In vitro (human scar fibroblasts and mouse primary macrophages) and in vivo (rat wound models and rabbit ear wound models) studies were conducted and demonstrated that sHA/G-GM not only improves conductivity to fibroblast activity regulation but also combines with interleukin-4 to promote macrophage phenotype switching. These results strongly suggest that sHA/G-GM synergistically amplifies endogenous electrophysiological functions and modulates the immune microenvironment to realize scarless wound healing. Therefore, the electrical and immune stimulation-based sHA/G-GM provide an effective approach to synergistically realize scarless wound healing in the future. [ABSTRACT FROM AUTHOR]