Thermoresponsive Biodegradable Hydrogel Combined with Photothermal and Chemodynamic Therapies To Eliminate Biofilms and Accelerate Infected Wound Healing

Bacterial wound infection tends to cause intense inflammation, while a lack of oxygen can lead to the destruction and contraction of blood vessels in the wound microenvironment. Here, a degradable hydrogel (denoted as PBCB hydrogel) was constructed with gelatin methacrylate (GelMA), tannic acid (TA), and polyphosphate (PolyP) by photopolymerization, and mesoporous polydopamine nanoparticles (MPDA) with berberine (BR), along with Cu and Bi nanoparticles grown in situ, were loaded into the hydrogel. PBCB hydrogel exhibits a high photothermal conversion efficiency (68.3%). Along with the degradation of the hydrogel, PolyP that was released showed a pronounced hemostatic effect in the mouse bleeding model by activating the clotting pathway. Under irradiation, PBCB hydrogel could constantly release BR, Cu²⁺, and TA, and 99.34% of methicillin-resistant <i>Staphylococcus aureus</i> (MRSA) and 99.82% of <i>Escherichia coli</i> (<i>E. coli</i>) were killed <i>in vitro</i>. <i>In vitro</i> experiments indicated that the PBCB hydrogel is capable of inhibiting and dismantling biofilm formation, as well as attenuating the expression of virulence factors. <i>In vivo</i> experimental data revealed that PBCB hydrogel-mediated synergistic chemodynamic therapy and photothermal therapy had a great promotional effect on wound sterilization and recovery. Our work demonstrated that the PBCB hydrogel can be used for bacterial biofilm removal and wound hemostasis, disinfection, and healing.