| Biomedical device-associated infection is a major challenge in modern clinical medicine,presenting a devastating threat to human health.It may lead to serious complications and heavy burdens on the healthcare system.Bacteria are the main pathogens that cause infections,and multidrug resistant(MDR)bacteria are particularly dangerous,as they are difficult to treat and even life-threatening.Bacterial adhesion to medical device surfaces is the main cause of medical device-associated infections.Traditional antibacterial surfaces have poor biocompatibility,limited functionality and a lack of bioactivity,which cannot meet the demands of anti-infection applications.Therefore,it is essential to functionalize the medical device surface with anti-bacterial and multifunctional coatings.This thesis proposes using natural polymers to prepare film-forming solutions by reasonably controlling the ratios of film-forming components,crosslinking components and antibacterial components.The Schiff base structure that is responsive to the weakly acidic environment was introduced to crosslink various components.A volatilization film-forming method was used to modify antimicrobial coatings on medical device surfaces.By one-step modification of volatilization,a stable long-term adaptive antibacterial coating was constructed on the surface of a temporary implant for treatment of infection after fracture fixation.By rational design of the crosslinking components of the film-forming solution,an antibacterial,anti-fouling and lubrication coating was constructed on the surface of medical catheters for the treatment of urinary tract infections.Furthermore,this thesis expanded the possibility of rational design of antibacterial components and more convenient film-forming schemes.An anti-fouling and anti-multi-drug resistant bacterial infection coating was constructed on hernia patches for the treatment of MDR bacterial infection.The volatilization film-forming method had the advantages of convenience,flexibility and universality.Meanwhile,this method could construct multifunctional antibacterial coatings on different implanted medical device surfaces through the reasonable design of different components to meet different application scenarios.The detailed research contents are as follows:1.In order to treat the infection of different implant-associated medical devices effectively,as well as to solve the problem of frequent and recurrent infections,the first part of this thesis proposed to construct antibacterial coatings on the surface of medical devices,which had bacterial responsive release profile of antimicrobial agents.A natural polysaccharide,sodium alginate(SA),was oxidized and used to couple gentamicin(GS)through p H-responsive Schiff base structure.In this section,the modification strategies were improved and optimized,and a one-step volatilization film-forming method was proposed to build a selfadaptive antibacterial coating(Ti-GOG)on the surface of implants for orthopedics(Ti).Scanning electron microscopy verified that the coating thickness and uniformity were significantly improved,with a thickness of about 50 μm.After soaking in a physiological environment for 7 days,the antibiotics in the coatings were still stable and had a significant antibacterial zone of inhibition with a diameter of 8.85 mm,demonstrating good stability and the ability to effectively address delayed infections.TiGOG was able to kill 99% of bacteria in 5 cycles of antibacterial experiments,proving its effectiveness against recurrent infections.Blood compatibility experiment proved that Ti-GOG had good biocompatibility,which could be used for surface functionalization for medical devices.2.In order to verify the feasibility of the film-forming modification strategy,the second part of this thesis made more comprehensive performance verification of Ti-GOG in vivo and in vitro.The specific components of the solution were film-forming component,gelatin,crosslinking component,oxidized SA(OSA),and antimicrobial component,GS.SA was modified with different oxidation degrees to optimize the components.Ti-GOG3 had high antibiotic loading capacity(1.57 mg cm-2),which could effectively resist five times of recurrent infections,and also could inhibit severe bacterial infections with a density of 107 CFU m L-1 in in vitro antibacterial experiments with an antibacterial ratio of up to 99%.The in vitro experiments proved that Ti-GOG3 could self-adaptive release GS in a weakly acidic environment at p H=5.0,and after continuous release for 72 h,there was still 75.8% of the GS remaining,which could effectively respond to delayed infections.Moreover,Ti-GOG3 had good biocompatibility.Finally,the in vivo anti-infective performances were successfully verified in the rabbit tibial infected open fracture model.TiGOG3 could effectively inhibit infection and infection-related inflammation at early stage,and was beneficial for recovery of bone fracture at late stage.3.In order to expand the volatilization film-forming method to different medical devices,the third part of this thesis carried out a rational design of the cross-linking component for the medical application scenario of antibacterial and lubrication demand of urinary catheters.Xanthan gum(XG)was selected as the cross-linking component to build antibacterial,antifouling and lubricating coating(SR-GXG2)on silicone surface for urinary tract infection therapy.By coating and modifying different shapes of tubes and different substrate surfaces,the universality of the volatilization film-forming method was demonstrated.The excellent antifouling,lubrication and antibacterial properties of the coating were verified through water contact angle,friction force,surface adhesion test,and antibacterial experiments.The dynamic friction coefficient decreased by 98.73%,and the antibacterial ratio was higher than 98% in three cycles of antibacterial experiments.By designing a rational cross-linking component,a coating that meet the clinical application requirements of urinary catheters was constructed,demonstrating the flexibility of the modification strategy.The biocompatibility of the coating was verified by cell and blood compatibility tests.Finally,the antibacterial and lubrication properties of the SR-GXG2 were verified in the rabbit urinary tract infection model,which effectively killed 99.99% of bacteria and prevented the shedding of urinary epithelial cells.4.The previous three parts have proved the convenience,universality and flexibility of the volatilization film-forming method.In order to further expand the rational design of antibacterial components and the convenience of this method,the fourth part of this thesis designed a coating(PU-GHB)with good anti-adhesion and anti-multi-drug resistant bacterial infection for hernia mesh,which was applied to the treatment of MDR bacterial infection of abdominal wall hernia.Hyaluronic acid(HA)with good biocompatibility and hydrophilicity was oxidized at a low aldehyde degree as the crosslinking component,and BDP-6 was synthesized as the antibacterial component with reactive groups and synergetic antibacterial property for photothermal/photodynamic therapy(PTT/PDT).Through the quantitative function of each component,the fabrication method of the coating was further simplified and improved.One-step crosslinking method was realized to replace two-step crosslinking method.The in vitro experiments verified that the PU-GHB had good antifouling property,with a water contact angle decrease of 78.79%,and effectively killed 99% of MDR bacteria by PTT/PDT combination.Meanwhile,the antibacterial mechanism was studied.Finally,the biocompatibility and antibacterial properties of the PU-GHB were evaluated in a rat abdominal hernia MDR bacteria infection model.In summary,aiming at the infections of different medical devices,this thesis successfully constructed antibacterial functional coatings on different medical device surfaces through a volatilization film-forming method.This strategy had convenience,flexibility and universality.The constructed coating had been successfully applied to fight against infections caused by fracture fixation,urinary tract infection caused by cathether and MDR bacterial infection in abdominal hernia.This strategy has academic significance and application prospects for the prevention and treatment of infection induced by different medical devices. |
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