Multifunctional Toxin-Neutralizing and Antibacterial Cell-Mimicking Liposomes for Effectively Managing Wound...

During the healing process of infected wounds, tissue damage caused by pore-forming toxins (PFTs) secreted by bacteria, as well as sustained inflammatory cascades and abnormal collagen expression are key factors leading to delayed wound healing and scar formation. To address this challenge, a multifunctional cell-mimicking liposome (RM-OB@Lips) co-loaded with berberine (BBR) and Nintedanib (Ofev) is engineered, which synergistically integrates toxin neutralization, antibacterial activity, and anti-fibrotic properties to achieve scarless wound repair. The erythrocyte membrane modification enabled efficient α-hemolysin (Hlα) adsorption via ADAM10 (ADAM metallopeptidase domain 10) receptors, resulting in a 68% reduction in toxin levels at infection sites and a significant attenuation of tissue damage and apoptosis. Sustained release of BBR eradicated drug-resistant pathogens while modulating inflammation. In a murine Methicillin-resistant Staphylococcus aureus (MRSA)-infected wound model, RM-OB@Lips treatment significantly suppressed proinflammatory cytokine secretion (Tumor necrosis factor-α: 62.6%, Interleukin-1β: 70.0%, Interleukin-6: 57.7%) and markedly reduced inflammatory cell infiltration at infection sites, and the formulation achieved an 82% wound closure rate after 14 days. Furthermore, Ofev inhibited fibroblast-to-myofibroblast transition by downregulating α-smooth muscle actin (α-SMA) expression and restored physiological type I/III collagen ratios, yielding regenerated skin morphologically and functionally comparable to normal tissue. Critically, this study provides the first direct evidence linking PFTs clearance to scar prevention, establishing a novel therapeutic paradigm for drug-resistant wound infections through the coordinated actions of detoxification, antimicrobial intervention, and fibrosis suppression.