Multifunctional SISTP dressing integrating AI-screened hexapeptide for sustained antimicrobial release and redox homeostasis in infected wounds

Abstract Infected wound healing environments present dual challenges of microbial colonization and sustained oxidative stress, critically impairing patient outcomes. Developing advanced dressings capable of concurrent broad-spectrum antimicrobial action and redox homeostasis restoration remains an urgent clinical priority. Here, we engineered a multifunctional porcine small intestinal submucosa extracellular matrix dressing ( i.e. SISTP) integrated with AI-screened antimicrobial peptides (AMPs) via tea polyphenol-mediated coordination. The CRRI6 hexapeptide (Arg–Trp–Trp–Arg–Trp–Phe) demonstrated prolonged release kinetics (>6 h) from the SISTP scaffold, achieving ⩾90% eradication of E. coli and S. aureus . Radical scavenging assays confirmed SISTP’s capacity to neutralize reactive oxygen species, while in vivo studies revealed accelerated wound recovery in infected rat models through synergistic microbial clearance and oxidative stress mitigation. This study pioneers a bio-inspired strategy leveraging AI-optimized AMPs and polyphenol nanoengineering to address the multifactorial pathophysiology of chronic wounds.