A Bio-inspired Oriented Antibacterial Sericin Microneedles For Infected Wound Healing Improvement

Objective:To construct a bio-inspired oriented antibacterial sericin microneedles system and explore the application in the repair of infected wound healing.Methods: An oriented structure microneedles system was designed from lamprey teeth.Sericin was isolated from the silk fibroin deficient silkworm cocoon by high temperature alkali extraction,and used to fabricate the sericin microneedles system.To prepare the multifunctional microneedle system,zinc oxide nanoparticles was used as antibacterial agent and integrated to microneedles system.The sericin microneedles system was characterized by stereoscopic microscopes,scanning electron microscope,small animal imaging system in vivo and microcomputer-controlled electronic universal testing machine.The antibacterial activity of the system was evaluated by its inhibition of bacterial growth in vitro and in vivo.The biocompatibility of the system was investigated by hemolysis and cell experiments.To evaluate the effect of the oriented antibacterial sericin microneedle system on wound repair,the system was applied to the mouse full-thickness skin excisional model,the injury sites were observed and photographed at different time points to calculate the wound healing rate.Wound skin tissue was collected at different time points,hematoxylin-eosin,masson’s trichrome,immunofluorescence stainings were performed to explore the effect of skin repair.Finally,the oriented antibacterial sericin microneedle system was tested in staphylococcus aureus-infected wound model.Results: The oriented antibacterial sericin microneedles system was constructed of two functional microneedle arrangements for drug delivery and directional traction.The needles were mainly composed of sericin and zinc oxide nanoparticles,had a complete structure and strong mechanical strength.The oriented microneedles could drag the edge skin to the center,causing the wound contracted to promote the wound healing.The zinc oxide nanoparticles were integrated as an antibacterial module,endowing the system with highly bacterial suppression.In vitro antibacterial experiment showed that it could effectively inhibit the growth of Gram-positive Staphylococcus aureus and Gram-negative Escherichia coli.In vivo antibacterial results showed long-term antibacterial effect.Cytotoxicity and hemolysis assay showed good biocompatibility.In the mouse full-thickness skin excisional model,wound healing was accelerated in the oriented antibacterial microneedles treatment group,histological results showed increased neovascularization,reduced wound scar,and more sebaceous gland and hair follicles formation,suggesting that the system could promote wound healing.Finally,in infected wound model,the combination of oriented microneedles and zinc oxide nanoparticles significantly promoted the repair of infected wounds.Conclusions: This study designed a bio-inspired oriented antibacterial sericin microneedles system with dually functionalized needles to provide penetration and directional traction.Sericin significantly improving skin repair via angiogenesis.Zinc oxide nanoparticles were integrated as an antibacterial module,endowing the OASM with highly bacterial suppression.It is believed that the synergy of these systems may effectively heal infected wounds,suggesting its clinically translational potential.