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[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]

• Decellularized ECM was prepared using porcine tendon tissue. • AC@PDA nanoparticles were fabricated. • Bioactive AC@PDA/ECM-G hydrogel was prepared. • Bioactive AC@PDA/ECM-G hydrogel displayed good physiochemical properties as a wound dressing. • In vivo results confirmed the potential of AC@PDA/ECM-G hydrogel as wound dressing for scarless wound healing. In this study, bioactive composite hydrogels were created using the decellularized extracellular matrix (ECM), GelMA, and Polydopamine-loaded Asiaticoside (AC@PDA) nanoparticles for use as wound dressings that could promote healing. A decellularization method was used to obtain ECM from porcine Achilles tendon tissue. AC@PDA nanoparticles were then synthesized and found to have a uniform spherical structure with good cytocompatibility, particularly when compared to PDA nanoparticles alone. The mechanical properties of the bioactive composite hydrogels showed good elasticity and shape recovery after compression, with a slight decrease in compressive strength due to the addition of nanoparticles. The formation of interpenetrating networks through the use of EDC/NHS was also found to improve the mechanical properties and moisture retention of the hydrogels. The PDA/ECM-G and AC@PDA/ECM-G hydrogels showed higher water absorption capacity and similar moist retention capacity to the ECM-G hydrogel. The microstructure of the hydrogels was observed through SEM, with the ECM-G hydrogel showing a dense and compact structure, while the PDA/ECM-G and AC@PDA/ECM-G hydrogels displayed a more porous and interconnected structure due to the presence of nanoparticles. In vitro cytotoxicity tests on human skin fibroblasts showed good biocompatibility for all hydrogels. The in vivo wound healing performance of the hydrogels was also tested on a full-thickness excisional wound model in mice, with the AC@PDA/ECM-G hydrogel showing the fastest wound closure without scarring and the highest-formed hair follicles. The AC@PDA/ECM-G hydrogel had the best performance in promoting wound healing. These results suggest that the bioactive hydrogel has the potential for use as a wound dressing. [ABSTRACT FROM AUTHOR]