An Excellent Antibacterial And High Self-adhesive Hydrogel Can Promote Wound Healing Driven By Its Shrinkage Under NIR

Objective:To improve the application defects of traditional wound dressing and the drawback of the wound that cannot heal in a short term,we designed a new wound dressing with active shrinkage ability,and then its performances were tested and evaluated.Subsequently,its repairing effect on wound defect was verified by animal experiments,aiming to provide a certain theoretical support for the clinical treatment of the wound.Methods:（1）Material preparation and characterization:Polydopamine（PDA）modified graphene oxide（GO）and silver（Ag）nanoparticles composite（PDA@Ag5GO1,Ag5GO1 indicates that the mass ratio of Ag to GO is 5:1）was synthesized,and then the different amount of PDA@Ag5GO1（0,0.5,1,and 2 mg/m L）was added to N-isopropylacrylamide（NIPAM）and N,N’-methylene bisacrylamide（BIS）to prepare temperature-sensitive hydrogels（PNIPAM）via chemical cross-linking,which were named as PNIPAM,PGH0.5,PGH1 and PGH2,respectively.The latter three are named as PGHs.Subsequently,Fourier transform infrared spectroscopy（FT-IR）,transmission electron microscopy（TEM）,and X-ray diffraction（XRD）were used to characterize the synthesized composite and hydrogel samples.The physical properties of hydrogels were studied by water content,swelling rate,degradation rate,adhesion test and NIR temperature response test.（2）Antibacterial and biocompatibility evaluation:The antibacterial performance of hydrogel was tested by plate counting method,disk-diffusion method and bacterial adhesion test.After that,MTT and phalloidin cytoskeleton staining methods were used to evaluate the survival rate,proliferation rate and cell morphology of fibroblasts.In addition,the antibacterial performance of hydrogel was tested by plate counting method,disk-diffusion method and bacterial adhesion test.（3）Wound healing evaluation:The skin defect models on the back of rats were established,and different experiment groups,including the control group,PNIPAM group,PGH0.5 group,PGH1 group and PGH2 group were used to treat wound defect,respectively.Meanwhile,the left and right control group（without NIR irradiation on the left side and NIR irradiation on the right side）were conducted to observe the skin healing effect and collect the tissue samples on the 5^th,10^th and 15^th day of treatment.Histopathological analysis of wound healing effect（H＆E,Masson,α-SMA）was performed to clarify the healing mechanism.Results:（1）PDA-coated Ag NPs dispersed around GO were observed in PDA@Ag5GO1by TEM,and the presence of Ag NPs was observed in PGHs hydrogel.The analysis results of physicochemical properties and surface morphology proved the successful preparation of PDA@Ag5GO1 composite and its existence in the synthesized hydrogels.The water content and swelling rate of the prepared hydrogel could reach90%and 4200%.The adhesion experiment showed that PGHs had high adhesion ability to different materials,and the adhesion force of PGH2 group was up to 35 KPa in pig skin simulation experiment.The results of temperature-sensitive response experiments showed that PGHs could produce strong centripetal contraction under the irradiation of near infrared light（NIR）.（2）Plate counting method confirmed that PGH2 hydrogel group had strong inhibition ability against Gram-negative bacteria（Escherichia coli）and Gram-positive bacteria（Staphylococcus aureus）.Disk-diffusion method confirmed that PGH1 and PGH2 hydrogels maintained good antibacterial activity within 3 days.Bacterial adhesion test showed that PGH1 and PGH2 hydrogels could effectively avoid bacterial adhesion on material surface.Cytotoxicity test results showed that the hydrogels were non-toxic to cells（cell survival rate>85%）and the cells had a normal cell morphology.（3）Animal experimental results showed that the wound treated with the combination of PGH2 and NIR almost fully healed within 15 days.The results of histological staining showed that hydrogel could significantly promote epithelial proliferation and collagen deposition.The results ofα-SMA staining showed that centripetal contraction of PGHs could promote the differentiation of fibroblasts into myofibroblasts.Conclusions:The novel hydrogel has excellent antibacterial properties,high adhesion,NIR response shrinkage,good biocompatibility,and fully healing of the wound within 15days.Therefore,the hydrogel will overturn the traditional wound treatment method,and has great potential in the clinical application of wound dressings.