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

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 FeCl 3 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. • Thermosensitive TCMBA is injectable at 25 °C, and instantly forms into elastic and biodegradable tissue adhesive at 37 °C to seal wounds. • TCMBA's photothermal properties enable mild PTT, promoting wound healing while killing bacteria and tumor cells. • NIR-assisted TCMBA treatment completely prevents tumor recurrence and metastasis while accelerating post-surgical wound healing. • TCMBA addresses wound closure, infection control, and cancer therapy, overcoming limitations in complex wound management.