Engineering programmable peptide hydrogels for chronic refractory wounds: A mechanism‐driven framework

Abstract Chronic wounds represent a significant hurdle in clinical care due to their ability to evolve into chronic refractory wounds (CRWs) as a result of disrupted healing progress. Unlike acute wounds, CRWs maintain a pathological microenvironment characterized by persistent infection, dysregulated inflammation, and hindered angiogenesis. Therefore, effective therapeutic strategies are urgently needed to address these complex, interconnected issues and promote wound healing. Among emerging solutions, peptide‐based hydrogels stand out due to their sophisticated molecular design and self‐assembly properties, making them ideal for advanced wound management. This review systematically explores the intricate pathophysiology of CRWs and emphasizes recent advances in the design of peptide‐based hydrogels for their treatment. Most notably, this review proposes a novel mechanism‐driven framework that classifies therapeutic strategies into a three‐tiered hierarchy, offering a conceptual roadmap for rational hydrogel design. This hierarchical, mechanism‐focused application framework progresses from basic structural support to single bioactive functional intervention to multifunctional synergistic therapeutic systems. Although challenges such as scalable production and long‐term biosafety remain, the development of intelligent and personalized peptide‐based hydrogels offers great potential to revolutionize advanced wound care.