Covalently Immobilized Neomycin in Self-Healing Hydrogel for Nonleaching Antibacterial Dressing in Diabetic Wound Healing

Bacterial infections remain a major challenge in the treatment of chronic diabetic wounds, primarily due to hyperglycemic conditions that favor microbial proliferation. Conventional hydrogels incorporating physically entrapped antibiotics are often limited by burst release and inadequate long-term antibacterial efficacy. To address this, we developed a covalently grafted antibacterial hydrogel system based on neomycin sulfate (N) conjugated to sodium alginate (SA) to form SA-N. This modified polymer was further combined with poly(vinyl alcohol) (PVA) and cross-linked via boric acid to establish an interpenetrating network structure, denoted as PBN hydrogels. Successful covalent conjugation of neomycin was verified by FTIR and 1H NMR spectroscopy. Rheological analysis under alternating strain demonstrated the hydrogel’s rapid self-healing behavior, a critical feature for dynamic wound environments. The PBN hydrogel exhibited strong broad-spectrum antibacterial activity, achieving inhibition rates of 98.03% against Staphylococcus aureus and 93.19% against Escherichia coli. Moreover, in a diabetic mouse wound model, treatment with the PBN hydrogel resulted in accelerated wound closure, reaching 96.59% after 21 days. Collectively, the PBN hydrogel demonstrates excellent biocompatibility, sustained antibacterial performance, and promising therapeutic potential for the management of chronic diabetic wounds.