Thermosensitive citrate-based mussel-inspired attack-defense integrated bioadhesives facilitate complicated wound healing.

Abstract

The treatment of complicated wounds remains unsatisfactory due to the lack of a comprehensive strategy synchronously addressing concomitant disease cure along with favorable wound healing. Herein, a family of thermosensitive citrate-based mussel-inspired bioadhesives (TCMBAs) were developed for the first time by mixing poly(ethylene glycol)-block-poly(propylene glycol)-block-poly(ethylene glycol)-incorporated and calcium-containing water-soluble injectable citrate-based mussel-inspired bioadhesive prepolymer with FeCl₃ in bicine solution. With a tunable minimum sol-to-gel transition temperature in the range of 28-42 °C, the optimized TCMBAs can be conveniently administrated at room temperature and instantly close wounds at body temperature. TCMBAs exhibit a suite of ideal material properties, including high wet tissue adhesion strength, rapid shape adaptability, self-healing capability, and high elasticity. Furthermore, they demonstrate fast biodegradability, excellent biocompatibility, and potent hemostatic ability. The intrinsic photothermal conversion efficiency of TCMBAs facilitates mild photothermal therapy (PTT), inducing a thermo-mediated cytotoxic effect that effectively eliminates both pathogenic bacteria and cancer cells. This multifunctional "attack-defense" property, combining antimicrobial and antitumor effects with barrier protection and regenerative functions, was demonstrated in infected and cancerous wound models. TCMBA-based treatment under NIR irradiation promoted healing of infected wounds and suppressed tumor recurrence and metastasis while accelerating wound closure. These results highlight TCMBAs as a highly promising platform for the treatment of complex and refractory wounds.