Construction Of Co-delivery System Of Lysostaphin And Vancomycin Based On Injectable Hydrogel And Its Prevention And Treatment To Biofilm

Introduction:With the aging of the population and the improvement of people’s requirements for quality of life,joint replacement surgery has been increasing year by year.However,joint prosthesis implantation has always faced a huge challenge:Prosthetic joint infection(PJI).At present,the conventional scheme for treating joint prosthesis infection is secondary revision surgery and long-term use of antibiotics,which brings a great economic burden to patients.The key to refractory prosthesis infection is the formation of biofilms on the surface of the prosthesis.This complex three-dimensional colony structure makes it difficult to achieve effective concentrations of antibiotics throughout the body and promote the formation of drug-resistant bacteria.At present,more and more bio-replaceable materials are used to prevent and treat prosthetic infections,but there is still a lack of a safe and efficient treatment to solve the intractable PJI that has formed mature biofilms.Gelatin is a water-soluble biodegradable polymer material.The degradation product does not produce an inflammatory reaction.It is chemically modified.Gelatin-based in-situ assembled hydrogels can be used as a powerful drug delivery system.Objectives:A kind of hydrogel capable of delivering vancomycin and glucocolytic enzyme was synthesized,and its characterization and antibacterial properties in vivo and in vitro were initially verified.Materials and Methods:The reaction of gelatin with N-succinimidyl 3(2-pyridyl dithio)propionate was used to synthesize pyridyl disulfide gelatin(GelSSPy)containing active pyridyl disulfide bond groups,and the four-armed Mercaptopolyethylene glycol(4-Arm-PEG-SH)forms in situ a cross-linked polyethylene glycol disulfide gelatin hydrogels via the formation of disulfide bonds.A co-deliverable hydrogel of vancomycin and lysostaphin was constructed to analyze its physical properties and biocompatibility.Biofilm models of Staphylococcus aureus,Methicillin-resistant Staphylococcus aureus(MRSA)and Escherichia coli were constructed on the surface of the titanium sheet.Ability,and observe the antibacterial ring,and ability to resist plankton.Finally,rat and mouse tibia infection models were constructed,and the in vivo anti-infective ability of drug-containing hydrogels was evaluated by X-ray,MRI and other methods.Results:This project successfully synthesized an injectable hydrogel with in-situ cross-linking ability and drug loading.It has good biocompatibility,can exist stably in the body,and can be degraded and absorbed by tissues within a certain period of time.In vitro experiments prove that hydrogels loaded with vancomycin and lysostaphin have certain ability to inhibit biofilm formation and lyse biofilm,and can inhibit the growth of plankton.This project successfully constructed and verified the tibial infection model of rats and mice.After treatment with hydrogel containing vancomycin and lysostaphin for 6 weeks,a certain anti-infective capacity was observed.Conclusions:Injectable GelSSPEG hydrogel with in-situ cross-linking ability synthesized on the basis of gelatin has good biocompatibility,and the release of vancomycin and lysozyme can inhibit the formation of biofilms by S.aureus and MRSA And the ability of bacteria to multiply,is expected to become a topical injection for the prevention and treatment of PJI.