Antioxidant/Antibacterial Nanofibers Loaded with Liposome-Encapsulated Proanthocyanidin Complexes: Machine Learning-Optimized Liposome Incorporated in Nanofibers Promotes Antibiotic-Free Wound Healing

Abstract Existing wound dressings are inherently limited by their insufficient antioxidant capacity, which fails to modulate the excessive oxidative stress at the injury site, alongside the well-recognized risks of bacterial infection and the escalating threat of antibiotic resistance that disrupts microbial homeostasis. To comprehensively tackle these drawbacks, this study introduces a strategy for promoting antibiotic-free wound healing using electrospun nanofibers loaded with proanthocyanidin cationic liposomes. Following the optimization of drug loading efficiency by machine learning, the cationic liposome was incorporated into nanofibers composed of chitosan/poly(vinyl alcohol)/mussel adhesive protein via electrospinning technology. The PVA/CS/MAP/PL nanocomposite membrane not only exhibits outstanding performance as a wound dressing (e.g., water absorption rate of 544.2 ± 24.8%), but also demonstrates significant antioxidant activity, with ABTS and DPPH radical scavenging rates of 92.2 ± 1.0% and 69.0 ± 1.2%, respectively. Furthermore, it exhibits an inhibition rate of 84.3% against Pseudomonas aeruginosa and 90.5% against Staphylococcus aureus. In vivo studies in mice show that wounds treated with PVA/CS/MAP/PL membrane achieve a healing rate of 98.4%. This work offers an, antibiotic-free solution for wound infection management, thereby alleviating concerns related to antibiotic resistance and systemic toxicity.