Multifunctional Antibacterial Surfaces Of Implantable/intervenfional Biomedical Devices

The morbidity of biomedical device-associated infections(BAI)is high,which has caused many serious consequences.It makes the patients suffer from pain and economic losses,even threatens the lives of patients.The main reason of BAI is the adhesion of bacteria on surfaces.The adhered bacteria then grow and reproduce rapidly,which finally forms biofilms that are difficult to remove.Therefore,modification of the surfaces of biomedical devices has very important research and application significance,which could enhance the antibacterial performances of biomedical devices.The mechanisms of traditional antibacterial surfaces mainly include release killing,contact killing,photo-induced killing,etc.However,there are still some limitations in the using process of traditional antibacterial materials,including single function,delayed action,short lifetime,low biocompatibility,and inducing drug resistance.In order to solve the above-mentioned problems,this dissertation proposed the enhanced antibacterial surfaces that comprised of two or more antibacterial mechanisms,which enhanced the antibacterial efficiency and minimized the damage to normal cells and tissues simultaneously.Based on this foundation,the surface chemical structures were rationally designed and constructed according to the needs of different types of medical devices.Through the introduction of bioactive components,the"antibacterial-antifouling" multifunctional surfaces were constructed.Furthermore,the strategy of constructing "antibacterial-osteointegrating promoting" multifunctional surfaces was also developed to enhance the therapeutic function of medical devices and realize multifunction of antibacterial surfaces.The detailed research contents are as follows:1.In the first part of this dessertation,the enhanced antibacterial strategy was applied with quaternary ammonium salt in mild photothermal conditions,which aimed to enhance antibacterial performances and ensure its biocompatibility.Au nanorods(Au-NRs)with high photothermal efficiency were modified onto the surface,and a small molecular bactericide,QDED,was conjugated to Au-NRs.The bactericidal property and biocompatibility of the surfaces were regulated by controlling the amounts of QDED.In the in vitro experiments,the high bactericidal efficiencies(>90%)was verified,especially against drug-resistant bacteria.At the same time,the functionalized surface had good biocompatibility,and the hemolysis rate was less than 5%.In addition,through the study of antibacterial mechanism,it was preliminarily confirmed that the functionalized surface mainly destroyed the cell membrane of bacteria and inactivate the enzymes to kill bacteria.Finally,in an animal model of subcutaneous infection,the good in vivo anti-infection performances were confirmed,and the functionalized surfaces did not cause significant toxicity and tissue irritation.2.Antifouling performance is the specific clinical need of abdominal hernia patches.Based on the results of the first part,an "antibacterial-antifouling"multifunctional coating was constructed on the surface of polyurethane(PU)by organic/inorganic hybrid coating in the second part.Au-NRs were immobilized onto PU surface by Au-S bond.Furthermore,thiol-modified polyethylene glycol(mPEG-SH),a super hydrophilic polymer,was taken for post-modification by "grafting onto" strategy to construct organic/inorganic hybrid coatings(PU-Au-PEG)with inherent antifouling property.PU-Au-PEG had stable cyclic photothermal properties,which could kill various kinds of bacteria,including multidrug resistant bacteria,under the irradiation of near-infrared light,and effectively prevent the adhesion and accumulation of dead bacteria on the surface.The quantitative results showed that the anti-adhesion efficiency of PU-Au-PEG was higher than 95%,and the bactericidal ratio exceeded 99.99%.The in vivo photothermal antibacterial performances were first confirmed by an animal model of subcutaneous implantation.Finally,infected hernia treatment was performed to demonstrate the anti-infection efficacy of PU-Au-PEG in clinical practice scenario.3.Dental implants have higher requirements for surface properties.In the third part,the multifunctional surface of "bactericidal-osteointegration promoting"properties was designed and constructed.Using the "grafting from" strategy,polymer brushes of glycidyl methacrylate(PGMA)as the molecular platform for subsequent functionalization were constructed by surface-initiated atom transfer radical polymerization(ATRP)on the surface of dental implants.Then,PGMA brushes were post-modified successively with ethanediamine(ED)by ring-opening reaction and Schiff base reaction,which produced functionalized Ti implants(Ti-AQ).The successful surface functionalization was confirmed by scanning electron microscope(SEM),X-ray photoelectron spectra(XPS)and water contact angle.The bactericidal performances were evaluated by live/dead fluorescence staining,and the bactericidal ratio was higher than 95%.Finally,the antibacterial and osteointergration-promoting properties of the materials were evaluated by the animal model of infected implantation.The integration ratio between Ti-AQ and the bone tissue was increased by?37%,which greatly improved the success rate of dental implants under infected conditions.In summary,a series of multifunctional antibacterial surfaces of implantable/interventional medical devices were successfully constructed according via different strategies.In this dessertation,enhanced antibacterial surface,"antibacterial-antifouling" multifunctional surface and"antibacterial-osteointegration promoting" multifunctional surface were constructed,which had efficient and safe bactericidal properties.The multifunctional antibacterial surface could satisfy the needs of clinical use,which has high academic significance and application prospect.