One-Step Physical and Chemical Dual-Reinforcement with Hydrophobic Drug Delivery in Gelatin Hydrogels for Antibacterial Wound Healing.

Gelatin-based bioadhesives, especially methacrylated gelatin (GelMA), have emerged as superior alternatives to sutureless wound closure. Nowadays, their mechanical improvement and therapeutic delivery, particularly for hydrophobic antibiotics, have received ever-increasing interest. Herein, a reinforced gelatin-based hydrogel with a hydrophobic drug delivery property for skin wound treatment was reported. First, photosensitive monomers of '-(2-nitrobenzyl)--acryloyl glycinamide (NAGA) were grafted onto GelMA Michael addition, namely, GelMA-NAGA. Second, gelation of the GelMA-NAGA solution was accomplished in a few seconds under one step of ultraviolet (UV) light irradiation. Multiple effects were realized simultaneously, including chemical cross-linking initiated by lithium phenyl-2,4,6-trimethylbenzoylphosphinate (LAP), physical cross-linking of uncaged dual hydrogen bonding, and hydrophobic drug release along with group disintegration. The mechanical properties of the dual-reinforcement hydrogels were verified to be superior to those only with a chemical or physical single-cross-linked network. The hydrophobic anticancer doxorubicin (DOX) and antibiotic rifampicin (Rif) were successfully charged into the hydrogels, separately. The antimicrobial tests confirmed the antibacterial activity of the hydrogels against Gram-negative () and Gram-positive () bacteria. The wound-healing assessment in mice further assured their drug release and efficacy. Therefore, this NAGA-modified GelMA hydrogel has potential as a material in skin wound dressing with a hydrophobic antibiotic on-demand delivery.