An Intrinsically Multifunctional Peptide Coiled-Coil Hydrogel with Controlled Dynamic Contraction for Active Infected Wound Management

Infected wound healing is hindered by a hostile microenvironment and limited active treatment options. While current hydrogels offer partial benefits, they struggle to simultaneously modulate the wound environment and physically close wounds. We design a smart hydrogel by integrating two peptide coiled-coil motifs: an antimicrobial tetramer and a stimuli-responsive dimer. Covalent polymerization of the antimicrobial tetramers, unfolded monopeptides derived from the coiled-coil dimer, and star-shaped polyethylene glycol (PEG) yields an intrinsically antimicrobial hydrogel in situ at the wound site. When treated by Zn 2+, the monopeptides fold and assemble into coiled-coil dimers within the matrix, triggering rapid, controllable hydrogel contraction that actively pulls wound edges together. Both coiled-coils also endow the hydrogel with intrinsic antioxidant activity. Furthermore, these coiled-coils function as reversible, sacrificial noncovalent crosslinks that effectively dissipate mechanical energy, synergistically enhancing the hydrogel’s toughness and resistance to swelling. Collectively, this intrinsically multifunctional hydrogel accelerates infected wound healing without the need for dressing changes and through a coordinated cascade of actions: on-demand dynamic wound contraction, bacterial eradication, reactive oxygen species scavenging, inflammation suppression, and promotion of re-epithelialization. This integrated design represents a significant advance toward smart, bioactive dressings capable of actively orchestrating multiple phases of the wound healing process.