Controllable Construction And Properties Of Antimicrobial Polymer Coatings On Titanium Alloys

Biomedical metal materials possess good mechanical properties and excellent biocompatibility,which have been widely used in orthopedics,dentistry,prostheses,various luminal stents,surgical instruments,and other fields.However,due to the inherent biological inertness and lack of antibacterial properties of metal materials,there are still some problems in clinical application.Bacterial-associated infection is one of the main reasons for implant failure,once the bacteria adhere to the surface of the implant,they will rapidly multiply to form a biofilm and cause infection,leading to implantation failure,which brings giant physical pain and economic burden to the patients.Therefore,the development of new medical metal materials with antibacterial properties has become an urgent issue.The construction of antibacterial coatings on the surface of metal implants such as titanium and its alloys has become an effective strategy to prevent implant infections.Active killing antibacterial agents(such as antibiotics,silver ions,antimicrobial peptides,cationic polymers,etc.)and passive repelling antibacterial materials(such as PEG,zwitterionic polymers,etc.)have been used for surface modification of implants to inhibit bacterial biofilm formation.In current studies,aimed at settling the problems associated with metal implantation infection,we developed three types of novel high-efficiency antibacterial coating on metallic substrates based on the strong coordination between phosphonate and metal substrate,as well as the high reactivity between NHS groups and amines.The functional PHMB and zwitterionic polymers are constructed on the surface of medical titanium alloys(TC4)through a simple two-step coating process.The antibacterial property of the coatings were systematically investigated.The specific research contents are as follows:(1)Construction and studies on the antibacterial properties of phosphonate/active ester block copolymer PHMB coating on the surface of TC4.Novel phosphonate/active ester block copolymers with different chain lengths were prepared by reversible addition-fragmentation chain transfer(RAFT)polymerization.The chemical structure and molecular weight of the block copolymers were accurately characterized by hydrogen nuclear magnetic resonance spectroscopy(¹H NMR)and gel permeation chromatography(GPC).The results indicated that the actual chain length of the phosphonate in the block copolymer was 29,and the active ester chain length was 7,29,64,respectively,and they were noted as:p DEMMP₂₉-b-p NHSMA₇(P₁),p DEMMP₂₉-b-p NHSMA₂₉(P₂),and p DEMMP₂₉-b-p NHSMA₆₄(P₃).PHMB was covalently constructed on the surface of the TC4 by a simple two-step coating process,and the wettability and chemical composition of the surface before and after the modification were characterized by the water contact angle and X-ray photoelectron spectroscopy(XPS).The experimental results proved that the block copolymers and PHMB were successfully covalently constructed on the surface of the TC4.The antibacterial ability of the surface of TC4 was systematically investigated by plate counting method,scanning electron microscope(SEM),laser confocal microscope(CLSM),etc.The experimental results have shown that the block copolymer and PHMB were successfully constructed on the surface of the TC4 substrate,and the surface PHMB content increased with the increase of the length of the active ester segment in the block copolymers and gradually enhanced the antibacterial effect of the substrate surface.When the active ester chain length was 64,the bactericidal rate of S.aureus and E.coli reached 100%.Besides,we have attained a structure-function relationship between the chain lengths of the block copolymers and the antibacterial efficiency combined with the systematically quantitative and qualitative analysis.And the coating also has good antibacterial ability in vivo.The PHMB coating is almost non-toxic and exhibiting good cell compatibility.(2)The construction and studies on the antibacterial properties of phosphonate/active ester random copolymer PHMB coating on the surface of TC4.Considering the stability of the coating and the grafting density of PHMB,five phosphonate/active ester random copolymers(n _DEMMP:n _NHSMA=10:90?90:10)were designed and prepared by random radical polymerization.The PHMB was covalently constructed on the metal surface through a simple two-step coating process.¹H NMR,GPC,water contact angle,and XPS were used to characterize the changes of chemical structure,molecular weight,metal surface wettability,and element composition of the random copolymers,respectively.These results showed that the series of random copolymers and PHMB coatings were successfully constructed on the surface of the substrate consistently.A series of antibacterial experiments(plate count,SEM,CLSM)have shown that the composite coating has high-efficiency and broad-spectrum antibacterial activity.As the molar ratio of phosphonate in the copolymer increases,the antibacterial effect on the surface of the material shows an"upper parabolic"trend.When the molar ratio of phosphonate to active ester in the random copolymer was 75:25,the synergy between the anchoring effect of the phosphonate component on the metal surface and the immobilization of the antibacterial PHMB polymer by the active ester component will achieve the best effect.The killing rate for S.aureus and E.coli reached 99.89%and99.99%,respectively.The 75:25-PHMB coating with excellent antibacterial properties was immersed in PBS to test the stability of the coating.The results showed that it had good antibacterial properties within 3 days,the antibacterial rate was 99.54%.The coating has a certain degree of universality.(3)The construction and studies on the antibacterial properties of zwitterionic/PHMB Kill-and-Repel dual function antibacterial polymer coating on the surface of TC4.Based on the prominent antifouling performance of zwitterionic polymers,they were added to the surface of a single function contact killing coating could significantly improve the surface antifouling effect,and release dead bacteria on the surface to achieve long-term antibacterial ability.Five kinds of phosphonate/zwitterionic/active ester block copolymers(p DEMMP-b-p(SBMA-co-NHSMA)with the same phosphonate segment length but in different ratios of zwitterionic and active ester segment length were prepared by RAFT polymerization.¹H NMR was used to characterize the chemical structure of the block copolymers,and the zwitterionic/active ester polymer was constructed on the surface of the titanium alloy by using the phosphonate structure in the copolymer,and then PHMB was grafted to the surface of titanium alloy.The synergistic antibacterial ability of p SBMA and PHMB on the titanium alloy surface was systematically investigated by the plate counting method,SEM,and CLSM.The experimental results showed that:p DEMMP-b-p(SBMA-co-NHSMA)and PHMB modified surface has an excellent dual-function antibacterial effect and the content of SBMA and NHSAM in the block copolymer has an important influence on the synergistic antibacterial property.When the molar ratio of SBMA and NHSMA was 50:50,the synergistic antibacterial performance was the best.The antibacterial rate of S.aureus and E.coli was 99.34%and 99.36%,respectively.Besides,the PHMB coating has good cell compatibility.