Antimicrobial Peptide-based Composite Hydrogel Used For Wound Healing Of Staphylococcal Infection

As the first line of defense of the human immune system,the skin plays an important role in protecting the body from external aggressions.There is often a risk of bacterial infection after skin injury.In the normal wound healing process,the stages of hemostasis,inflammation,proliferation and remodeling all occur in an orderly manner.Bacterial infection will interfere with these steps of skin repair,delay wound healing,and worsen the persistent infection of the wound site.Therefore,the development of a bioactive dressing that can quickly antibacterially,reduce wound site infections,and promote rapid wound healing is of great significance for wound healing caused by bacterial infections.In recent years,the antimicrobial peptide（AMP）material with broad antibacterial activity and the photodynamic therapy using photosensitizer（PS）to produce singlet oxygen（ROS）under a specific excitation light source to induce the damage and even death of pathogenic microorganism cells have gradually attracted the attention of researchers.In this study,a novel antimicrobial photodynamic peptide（AMP₂-Ce6）was designed by combining AMP and PS,and a compound hydrogel system was constructed by combining AMP₂-Ce6 with collagenⅢ（ColⅢ）and gelatin matrix to apply to wound healing research of Staphylococcus aureus（S.aureus）infection.The work completed in this paper is as follows:（1）The double-chain antimicrobial peptide（GKRWWKWWRR）₂KGGKG（AMP₂）was prepared by Fmoc solid phase synthesis method.The double-chain antimicrobial peptide has excellent antimicrobial activity.After coupling with chlorin e6（Ce6）,the stability of Ce6 was significantly improved.Induce cell and microorganism inactivation,and produce synergistic antibacterial effect with antimicrobial peptide.At the same time,in vitro antibacterial experiments also showed that AMP₂-Ce6 can effectively inhibit the formation of S.aureus biofilm and reduce the survival rate of bacteria.（2）The hydrogel dressings based on Gelatin are similar to the extracellular matrix,which can provide a moist repair environment for the wound surface and accelerate the speed of wound healing.ColⅢhas high biological activity and can promote collagen deposition and new blood vessel formation,thus becoming an important material for wound dressing preparation.We constructed a composite hydrogel system loaded with AMP₂-Ce6 and Gel-Col for in vivo clearance of S.aureus infection and promotion of wound healing.（3）By constructing a mouse model of S.aureus infection wound,the compound hydrogel was used for the treatment of S.aureus infection wound.Compared with the control group,the wound area of the mice in the compound hydrogel and irradiation group was significantly reduced.It is worth noting that the histological analysis of the infected skin tissue,On the10th day of treatment,normal skin tissue morphology was observed in the composite hydrogel and irradiation group,and the skin tissue structure was complete.Compared with the traditional hydrogels,the composite hydrogels loaded with AMP₂-Ce6 and Gel-Col can effectively eliminate the bacteria on the wound surface,shorten the wound healing time and improve the wound healing quality,showing its great potential as a wound dressing!...