Controllable Synthesis Of Zwitterion/phosphonic Acid Copolymers And Their Biomineralization-promoting Properties

Biomineralization is a process in which organic matrix regulates the nucleation and growth of inorganic minerals at a specific site in an organism,thus,the process of organic-inorganic complex mineralized tissues with specific structure and shape is obtained.Bone and teeth are the two basic and widely existing natural biomineralized tissues in vertebrates.Their main inorganic components are hydroxyapatite(HAp),and they both have layered and orderly structure and excellent mechanical properties.However,with the increasing aging of the population and the change of people's diet,some orthopedic and dental diseases,such as dental defects,periodontitis,osteoporosis and bone defects are seriously affecting human health.Bionic mineralization is a process in which inorganic minerals are regenerated in vitro using functional organic templates,preparing hydroxyapatite by biomimetic mineralization has gradually become a research hotspot due to its controllable process.To address the problem of poor remineralization/antifouling ability of tooth and orthopedic metal implants,this paper based on the excellent antifouling/mineralization promoting properties of zwitterionic polymers,combined with the stable anchor ability and excellent promoting mineralization of phosphonic acid,we designed and synthesized a new type of zwitterionic polymers,and grafted them to medical metal and demineralized enamel/dentin surface.The detailed research contents are as follows:(1)Construction and remineralization/antifouling promoting properties evaluation of zwitterionic/phosphonic acid random copolymers on titanium surface.First,sulfobetaine zwitterionic/phosphonic acid random copolymers were prepared by random radical polymerization,and the corresponding MMPA homopolymer was prepared through reversible addition fragmentation chain transfer(RAFT)polymerization.Then they were coated on titanium substrates through one-step coating process.The chemical structure and molecular weight of the polymers were characterized by ~1H NMR and GPC.The wettability and surface elemental compositions of the modified titanium substrates were measured by water contact angle(WCA)and XPS.The antifouling and remineralization properties of the modified titanium substrates were systematically studied by protein adsorption,bacterial adhesion,platelet adhesion,cell adhesion and in vitro mineralization experiments.On this basis,the polymer coatings were constructed on different metal surfaces,and the effect of polymer coatings on improving the remineralization ability of different metals was investigated.~1H NMR results showed that we have synthesized zwitterionic/phosphonic acid copolymers and the homopolymer accurately.WCA and XPS tests showed that the prepared polymers have been successfully constructed on the surface of titanium,and the wettability of modified TC4 surfaces could be improved significantly.The structure-activity relationship between polymer compositions and their abilities to improve the surface antifouling/remineralization performance of TC4 substrates was systematically established through a series of experiments,such as bacterial adhesion,protein adhesion,platelet adhesion,cell adhesion and in vitro mineralization.The experimental results showed that four kinds of random copolymers modified titanium surfaces could significantly inhibit protein adsorption,platelet adhesion,bacterial adhesion and cell adhesion within 24 h,but p MMPA homopolymer modified titanium surfaces did not have such performance,which suggested that zwitterionic components played an antifouling role;The results of remineralization experiments showed that the five polymers could effectively promote the surface remineralization of TC4 surfaces,and p MMPA had the best performance.In addition,we have coated these polymers on different metallic substrates and then proved that zwitterionic/phosphonic acid copolymers and phosphonic acid homopolymer were a kind of universal coating materials to promote remineralization of different metallic surfaces.(2)Study of zwitterionic/phosphonic acid random copolymer in promoting dentin function reconstruction.The zwitterionic/phosphonic acid random copolymer(n SBMA:n MMPA=6:4)and p MMPA were coated on the surface of demineralized dentin.The wettability and surface elemental compositions of the coated dentin were measured by WCA and XPS.The effects of the two polymers on the antifouling properties of demineralized dentin surfaces were systematically studied through a series of experiments,including protein,biofluid adsorption,bacterial adhesion and whole blood contact.In vitro and in vivo mineralization experiments were conducted to study the effects of two polymers on the remineralization properties of demineralized dentin.WCA and XPS tests showed that the two polymers were constructed on the demineralized dentin surface successfully and improved the wettability of the dentin surface significantly.The results of antifouling experiments showed that the surface of demineralized dentin grafted with zwitterionic/phosphonic acid random copolymer could inhibit protein,biofluid,blood and bacterial adhesion within 24 h significantly compared with the demineralized dentin surface grafted with phosphonic acid homopolymer.The results of in vitro and in vivo remineralization experiments showed that both polymers could induce the regeneration of apatite minerals on the surface of demineralized dentin and inside the dentin tubules,thus seal the exposed dentin tubules effectively.(3)Study of zwitterionic/phosphonic acid random copolymer in promoting enamel function reconstruction.The two polymers prepared in(2)were coated on the surface of demineralized enamel by a one-step coating process,respectively.The wettability and surface elemental compositions of the modified enamel were measured by WCA and XPS.The effects of the two polymers on the antifouling properties of demineralized enamel surfaces were systematically studied by means of a series of experiments,such as protein,biofluid adsorption,bacterial adhesion and whole blood contact.In vitro and in vivo mineralization experiments have proved that both the two polymers could improve the remineralization properties of demineralized enamel.WCA and XPS tests showed that the two polymers have been grafted on the demineralized enamel surface successfully.The antifouling experiments results demonstrated that the amount of protein,biofluid adsorption,blood adhesion and bacterial adhesion on the surface of demineralized enamel grafted with copolymer were decreased significantly within 24 h.The results of in vitro and in vivo remineralization experiments showed that both polymers could effectively promote the regeneration of apatite minerals on the demineralized enamel surface,finally achieve the purpose of repairing enamel defects.