Charge Microenvironment and Bioactivity of In Situ-Formed PEG-RGD Dual Hydrogel Dressings Promote Wound Healing

Abstract

Large skin wound heal involves a complex biological process with overlapping phases, facing challenges from fibroblast proliferation, immune response, and extracellular matrix (ECM) remolding. Hydrogel dressing serves as a temporary barrier for injured tissue from exogenous infections while providing an advantageous microenvironment for cellular regeneration. However, traditionally molded hydrogels through catalyzed or triggered crosslinking into fixed size and strength prior to treatment struggle to integrate tightly with irregular wound surfaces, leading to dressing detachment and wound exposure in areas with high curvature and mobility. Here, we designed CGRGDGC peptide enantiomers, incorporating with 4 arm-PEG-maleimide, to in situ form functional and morphologically matching dual-phasic hydrogel dressing. In situ elastic hydrogel dressing forms within 10 mins after applying, with storage modulus of 1300 Pa and internal porous network. The peptide incorporation increased the surface potential to ~370 mV, 2-fold of PEG hydrogels. Bioactive L-peptide hydrogel exhibited strongest immunomodulation and skin regeneration enhancement, while non-bioactive D-peptide hydrogel also showed significant promotion compared to PEG hydrogel. We demonstrated that both charge microenvironment and bioactivity of hydrogel dressing regulate immune response and promote wound healing after skin injury. This research provides novel insights and strategies for that non-ligand peptide sequences achieve biological functions through modulating molecular potential and that adjusting charge microenvironment and incorporating bioactive peptides through introducing peptide phase enhance skin regeneration.