New Antibacterial Hydrogel Wound Dressing For Promotion Of Chronic Wound Healing

The prolonged healing time of chronic wounds will increase the possibility of pathogens invasion,leading to deterioration of the wound environment and further hindering wound healing.Traditional dressings are no longer suitable for clinical wounds due to defects such as dryness,poor adhesivity,lack of antibacterial properties and susceptible to secondary injury.Hydrogel has been successfully used in the treatment of skin defects,bacterial infections,burns,diabetic feet and other wounds,due to its good biocompatibility,high water content and unique three-dimensional network structure.The use of antibiotic may aggravate the bacterial resistance issue.Therefore,it will be more beneficial to endow the hydrogels with antibacterial capability by incorporation of cationic polymers and metal nanoparticles,both of which are inherent broad-spectrum antibacterial candidates.Due to the conventrational wound dressing strategies are ineffective and insufficient against chronic wounds,development of a new hydrogel wound dressing with inherent antibacterial properties,good biocompatibility,tissue adhesion properties,mechanical properties and promoting chronic wound healing is highly desired.Herein,we developed a hydrogel dressing with good mechanical properties,shape recovery properties,adhesivity,conductivity,cell compatibility and antibacterial properties.In this study,physicochemical properties,rheological and mechanical characteristics,electrical conductivity,antibacterial properties and biocompatibility of the hydrogel were studied.A mice model of diabetic full-thickness skin defects was used to evaluate the wound healing performance of the hydrogel.The specific research content can be divided into the following three parts:（1）In this study,self-assembled lithocholic acid（LCA）nanotubes were used as soft templates to provide pyrrole（Py）adsorption sites,and Ag⁺induced Py to oxidize and polymerize in situ on the surface of LCA nanotubes while reducing Agnanoparticles（AgNPs）in situ,and finally obtained AgNPs-encapsulated polypyrrole（AgPPy）nanotubes.（2）PPCA hydrogel was prepared by dispersing AgPPy nanotubes with antibacterial activity and conductivity as nanofillers into mixed solution of cobalt ion(Co²⁺),cationic polymer polyethyleneimine（PEI）,anionic monomer acrylic acid（AA）and crosslinking agent N,N’-methylenebisacrylamide（BIS）by free radical oxidation polymerization.The autocatalytic ability of PEI and AgNPs accelerated the oxidative polymerization process of free radicals,which leads to the gelation of PPCA hydrogels in a short time.The good conductivity of PPAC hydrogel was attributed to the uniform distribution of AgPPy nanotubes in the PPCA hydrogel framework.There were high density hydrogen bonds and electrostatic interactions between PEI and PAA chains,and ion coordination interactions between Co²⁺and PAA.These non-covalent interactions were dynamic and reversible and can be used as sacrificial bonds to break and regenerate to dissipate energy,thus improving the mechanical properties of hydrogels.The mechanical experimental results showed that PPCA hydrogel has good tensile properties and compression recovery properties,and was consistent with Young’s modulus of human skin（7-33 k Pa）.The PPCA hydrogel has good swelling and moisturizing ability.In addition,PPCA hydrogel has good adhesion due to the existence of a large amount of-NH₂ groups and-COOH groups.（3）The biological functions of hydrogels,such as cell compatibility,blood compatibility,antibacterial properties,and full-thickness wound healing of diabetic skin were studied.The results of cell experiments in vitro showed that PPCA hydrogel has good cytocompatibility,which may be attributed to the existence of conductive AgPPy nanotubes to promote cell proliferation.The results of hemolysis test showed that the hemolysis rates of hydrogels were all less than 5%,indicating that the hydrogels had good blood compatibility.The results of the antibacterial experiment in vitro showed that PPCA hydrogel had excellent antibacterial properties against Escherichia coli and Staphylococcus aureus.This is due to the inherent antibacterial properties of Co²⁺and PEI and the broad-spectrum germicidal efficacy of AgNPs,which leads to the high antibacterial ability of PPCA hydrogels.The results of animal experiments showed that PPCA hydrogel as a wound dressing can promote full-thickness wound healing of diabetic skin,this was because Co²⁺can promote the formation of capillaries in wound tissue,and AgPPy nanotubes give hydrogel electrical activity and antibacterial function to further accelerate wound healing.In short,the PPCA hydrogel wound dressing has good mechanical properties,adhesion properties,electrical conductivity,swelling and moisturizing properties,biocompatibility,antibacterial properties and wound healing properties.These results suggest its great potential for the treatment of chronic wound healing.