Dynamic and Thermostable Supramolecular Hydrogels via Peptide Nanoparticle Crosslinking for Enhanced Wound Healing

Abstract Designing supramolecular hydrogels that simultaneously exhibit dynamic behavior and robust stability remains a fundamental challenge, as conventional strategies to enhance thermal and anti‐swelling properties often compromise injectability, self‐healing, and responsiveness. Here, a minimalist two‐component hydrogel system is reported, formed by crosslinking self‐assembled peptide nanoparticles with four‐arm polyethylene glycol (PEG) via click chemistry. The resulting hydrogel uniquely combines thermostability and anti‐swelling behavior with dynamic features such as shear‐thinning, injectability, and self‐healing. The hydrophobic effect driving nanoparticle formation imparts water‐repellency and thermal resilience, while the reversible supramolecular interactions enable structural adaptability. The hydrogel also demonstrates multi‐responsiveness, antibacterial activity, and cargo‐grafting capability. In vivo studies confirm its efficacy in accelerating the healing of infected wounds, with pronounced anti‐inflammatory and pro‐angiogenic effects. This work introduces a new design paradigm for multifunctional supramolecular hydrogels, transforming component simplicity into performance complexity.