Mechanically Active Adhesive Hydrogels Driven by Peptide Self-Assembly for Accelerated Healing of Diverse Wounds.

Emerging mechanically active hydrogels offer a promising therapeutic strategy for accelerating wound healing by promoting wound contraction. However, existing approaches to drive hydrogel contraction remain limited, and their inherent drawbacks hinder broader application across diverse wound types. Herein, a stimuli-responsive peptide self-assembly system is introduced into the hydrogel network, resulting in a novel mechanically active hydrogel (denoted as GHPD) capable of assembly-driven contraction and robust tissue adhesion. The GHPD can rapidly form in situ and adhere firmly to wound tissues, while volume contraction triggered by peptide self-assembly facilitates active wound closure. Notably, the mechanically active GHPD hydrogel is successfully applied to complex wounds in multiple scenarios, including superficial wounds (rat full-thickness skin defect) and internal injuries (acetic acid-induced gastric ulcer model). In addition, the mechanical stimulation generated by hydrogel contraction induces macrophage polarization, reduces pro-inflammatory factors, promotes vascularization and other pleiotropic effects, collectively contributing to significantly improved wound healing. This work not only proposes a new strategy for driving hydrogel contraction via peptide self-assembly, but also offers innovative insights into the application of engineered mechanically active hydrogels to accelerate the healing of diverse wound types in clinical settings.