Gentamicin‐Linked Supramolecular Hybrid Hydrogels: Mechanically Robust Cucurbit[7]Uril‐Based Networks for Prolonged Infection Control

ABSTRACT Burn wound infections, caused by Staphylococcus aureus (S. aureus) and Pseudomonas aeruginosa (P. aeruginosa) , remain a major clinical challenge, delaying healing and increasing the risk of mortality. Gentamicin sulfate (GEN) is a broad‐spectrum antibiotic widely used for infection control. However, conventional GEN‐loaded hydrogels often suffer from burst release and inadequate mechanical strength for sustained wound coverage. Here, we report GEN‐loaded (0.11–0.72 w/v%) supramolecular hybrid hydrogels (GEN‐SHHs) in which GEN acts in a dual role as both an antimicrobial and a dynamic physical crosslinker through cucurbit[7]uril (CB[7]) host–guest interactions within a clay‐reinforced hydrogel network. This polymer network gels within 5 s and achieves an exceptional elastic modulus (up to ∼270 kPa), the highest reported for CB[7]‐based or antibiotic‐crosslinked hydrogels. This integrated design achieves sustained GEN release for 14 days at concentrations above the minimum inhibitory and bactericidal thresholds for S. aureus and P. aeruginosa , yielding complete eradication (>99.999%) at GEN loadings ≥0.44 w/v%. Prolonged antimicrobial efficacy is further confirmed by persistent inhibition zones over two weeks. GEN‐SHHs also maintain high cytocompatibility (>94% viability) with human dermal fibroblasts (HDFs) and epidermal keratinocytes (HEKs). These results establish GEN‑SHHs combining dynamic bonding, high stiffness, and durable antimicrobial performance for advanced infection‐resistant wound dressings.