Glyco-engineered multifunctional hydrogel with bacterial fishing hooks for targeted bacterial eradication and enhanced wound healing

Infection with drug-resistant bacteria in hospitals significantly hinders wound healing, resulting in a high mortality rate among affected patients. In this study, we developed a multifunctional dextran-based hydrogel platform that effectively captures and eliminates carbapenem-resistant <i>Pseudomonas aeruginosa</i> (CRPA) from wounds. By grafting glycoligands (galactose and fucose) onto the three-dimensional hydrogel matrix and two-dimensional black phosphorus nanosheets, we substantially enhance the selective capture of CRPA through multivalent carbohydrate-lectin interactions. These glycoligands as hooks not only improve the stability of black phosphorus nanosheets, reducing their susceptibility to degradation, but also enable the hydrogel platform to spontaneously capture bacteria, localizing thermal ablation at the site of infection. This dual-action approach not only enhances bactericidal efficacy but also minimizes adverse effects on surrounding healthy tissue. Furthermore, the hydrogel exhibits multifunctional properties, including biocompatibility, anti-inflammatory activity, hemostasis, adsorption, adhesion, self-healing, and sufficient mechanical performance, ensuring its <i>in vivo</i> therapeutic efficacy in a mouse model of CRPA-induced cutaneous infections. This study demonstrates the utilization of glycohooks to optimize the photothermal effects of black phosphorus nanosheets, potentially opening new avenues for precisely synergistic therapies based on photothermal nanomaterials to combat antibiotic-resistant bacteria.