Application Of Multifunctional Hydrogels Incorporated With Photothermal Therapy Against Drug-resistant Bacterial Wound Infection

Bacterial infection and subsequent difficulties in wound repair are increasingly serious medical and health problems.Bacterial inactivation is a critical step in the treatment of wound infections.Therefore,developing wound dressings with antibacterial functions is an effective method for dealing with these infections.Hydrogels are hydrophilic polymer networks formed by physical or chemical interactions,which are widely used in the biomedical field due to their excellent biocompatibility and unique physicochemical properties.Hydrogels have good water absorption properties,which are beneficial for absorbing tissue fluid that seeps from wounds.In addition,the porous network structure of hydrogels is conducive to the dispersion and stability of active substances,making them promising carriers for photothermal agents（PHTAs）.Photothermal therapy（PTT）is a treatment that utilizes the characteristic of PHTAs to convert light energy（near-infrared）into thermal energy,achieving thermal inactivation of bacteria.PTT has broad prospects in the treatment of wound infections due to its simplicity,low invasiveness,and controllable photothermal properties.This study designed two multifunctional hydrogel dressings loaded with photothermal agents for the treatment of wound infections.The specific research content and results are as follows.Herein a biocompatible wound dressing is conveniently constructed by incorporating(Sr_0.6Bi_0.305)₂Bi₂O₇（denoted as SBO）with excellent photothermal performance into a facile antibacterial hydrogel（gel）obtained from multiple physical crosslinks among Ag⁺,carboxymethyl chitosan and polyacrylic acid.The prepared SBO gel features excellent bactericidal activities,hemostasis,adequate mechanical properties,adhesiveness and adsorption capacities to bacterial cells and toxin.The gel can disperse SBO homogeneously in the network and SBO effectively convert visible light energy into localized heat for synergistic sterilization.This is the first report of SBO as a photothermal agent applied in anti-infection treatment.In vitro assays confirm the potent broad-spectrum bactericidal activities of SBO gel to some common pathogens and drug resistant strains such as MRSA and CAPA.Mice model of MRSA-induced wound infections verified the practical efficacy of SBO gel in combating bacterial infections and accelerating wound healing.All of these results highlight the potential application of SBO gel in drug-resistant bacteria associated wound management.Moreover,In the second study,a novel multifunctional photoresponsive hydrogels combining glycohook-equipped black phosphorous nanosheets（BP）has been designed for wound healing.The developed nanosheets,namely,BP@NH₂-G+F,were prepared by coating two types of glycomimetic compounds（Galactoside and Fucoside）for specifically block bacterial Lec A and Lec B lectins,respectively,on the surface of BP nanosheets through electrostatic interaction.This strategy does not only improve the biocompatibility and physiological stability for the BP nanosheets,but also endows the theranostic nanoplatform with strong PTT capability in NIR region.Meanwhile,a glyco modified hydrogel（denoted as T-Gel）dressing can be conveniently obtained through copolymerization of the complex formed by Magnolol（Mag）,3-acrylamido phenylboronic acid（APBA）（the formation of boronate ester bond）,acrylamide and oxidized dextran complexation（ODC）that decorated with two types of glycomimetic compounds through forming Schiff base bonds.Herein the BP T-Gel is conveniently constructed by incorporating BP@NH₂-G+F into the T-Gel.The resulting hydrogel features adequate mechanical properties,self-healing capability and tissue adhesiveness.Furthermore,in vitro and in vivo assays confirm this novel hydrogel formulation shows the most efficient killing against PA and CRPA infection through lectin blocking and the near-infrared-light-induced photothermal effect of glyco modified black phosphorous synergistically.In addition,it can not only realize anti-oxidation,but also facilitate hemostasis to accelerate wound healing.This advanced hydrogel is expected to be an alternative wound management treatment strategy against the ever-threatening drug-resistant infectious diseases.