Fabrication And Properties Of Zwitterionic Anti-biofouling Coatings Based On Multiple Synergistic Effects

When implanted materials,such as artificial heart,artificial bone,artificial lung,vascular stent,intraocular lens,etc.,are in contact with blood or tissue fluid,it is easy to attach a layer of biofoulants on the surface,inducing thrombosis or bacterial infection.If thrombosis or bacterial infection happens,another operation and a huge economic burden,even the life-threatening situation,will be brought to the patients.Therefore,preparation of a stable and long-lasting anti-biofouling coating by surface modification technology has become one of the key issues to improve the biocompatibility of biomaterials,reduce complications and prolong the clinical service life.Inspired by the antifouling and anticoagulation of the outer membrane structure of the cell,the cell mimetic outer membrane structure polymers with antifouling and antifouling-bactericidal properties were designed and synthesized.Then,a series of stable cell mimetic outer membrane structure polymer coatings were fabricated by covalent-covalent interaction or covalent-noncovalent synergistic effect on the biomaterials.(1)A series of random copolymers,poly(MPC-co-GMA-co-TSMA)(PMGT),was synthesized and used to modify the APTES activated PDMS surface(PDMS-A)through an incubation/post-crosslinking technique.When PDMS-A which possessed NH₃⁺,-NH₂ and Si-OH/Si-OC₂H₅ surface functional groups,was incubated in PMGT solution,the epoxy and Si-OCH₃ ligands in the polymer chains were both possible to react with their complementary surface receptors.AFM,XPS,SCA and antifouling results confirmed that the anchoring of polymer chains and the growth of coating thickness of PMGT could be well-balanced by adjusting the content of epoxy and Si-O(CH₃)₃ in the polymer chains,showing positive cooperativity of dual-covalent interactions during the coating process.The post-crosslinking under TEA-containing moisture atmosphere is then applied to achieve a highly crosslinked polymer coating with zwitterionic moieties oriented towards the outer surface and tailored hydrophilicity,coating stability and antifouling properties.It indicated that the incorporation of multiple covalent interactions during coating process is promising to be a more flexible platform to fabricate the stable functional coatings based on a cooperative mechanism,giving rise to the long-term and controllable surface properties.(2)A ternary random copolymer poly(MPC-co-CMA-co-Az MA)(PMCA)containing phosphorylcholine group,cholesterol group and azidophenyl group was synthesized and drop-coated onto polypropylene(PP)surface,followed by simple UV irradiation.The physisorption of Chol moieties contributed to the spreading and aggregation of PMCA polymer chains,leading to the formation of a dense and relatively uniform zwitterionic polymer coating with continuous and nanogranular surface texture.The immobilization of such surface morphology could be facilitated by the subsequent chemical crosslinking of azidophenyl groups under UV irradiation.AFM,XPS,SCA and coating stability results showed that the combination of physisorption and post-chemical crosslinking procedure could synergistically improve the durability of the resultant PMCA coating,even after immersion in 75%ethanol for 6 h,ultrasonication in 1%SDS for 15 min,heat at 100°C for4 h or being placed for 3 months in air.Cytotoxicity,protein adsorption and platelet adhesion experiments demonstrated that compared with the bare polymer substrates,the obtained PMCA coating improved the blood compatibility effectively.(3)Dopamine(DA)is selected as a molecule for multiple interaction model.It is co-deposited onto PP surface together with a designed polymer poly(MPC-co-AEMA)(PMA)which contains both phosphorylcholine and primary amine side groups.Different non-covalent bonding(?-?stacking,cation-?,hydrogen bonding)and/or covalent bonding(dopamine oxidative coupling,Michael addition and/or Schiff base reaction)among DA,PMA and PP synergistically lead to the formation of robust biomimetic coating on PP surface through a one-step co-deposition procedure.With PDA coating and PDA-PMPC co-deposition coating as control,AFM,XPS,SCA and coating stability test confirmed the positive contribution of reactive PMA polymer chains to the regulation of PDA deposition process through incorporation of Michael addition and/or Schiff base reaction between DA and PMA chains.The resultant PDA-PMA co-deposition coating showed greatly improved durability and greatly improved resistance to protein adsorption,platelet adhesion and bacterial adhesion(S.aureus,E.coli and P.aeruginosa).(4)Three kinds of ternary random copolymers containing phosphorylcholine,primary amine and quaternary ammonium groups(PDA-PMAQ1C,PDA-PMAQ8C and PDA-PMAQB)were designed and synthesized to co-deposit with dopamine through one-step co-deposition procedure.The cooperation of multiple interactions between DA and PP or copolymers leads to the formation of durable co-deposited coatings.When the contents of phosphorylcholine groups in the polymer chains are 30-50%,the resultant co-deposition coatings possessed the antifouling properties and bactericidal performance simultaneously due to the co-existence of phosphorylcholine and quaternary ammonium groups.The layers exhibited excellent bactericidal properties even after 7 days of culture in suspensions of three pathogenic bacteria(S.aureus,E.coli and P.aeruginosa).(5)To achieve the coating surface with both antifouling and cell-growth promoting performance,dopamine,carboxymethyl chitosan(CMC)and PMA are used to co-deposit onto PP surface through one-step co-deposition procedure.The multiple interactions among dopamine,carboxymethyl chitosan,PMA73 and PP substrate drives the formation of a durable multifunctional coating.When the fraction ratio of CMC,PMA73 and dopamine is0.125:1:1,the achieved co-deposited coating had good resistance to FITC-BSA,bactericidal property and cell-growth promoting activity.It suggests that the balance of the content of CMC,PMA73 and DA is very important to regulate the multifunctional performance of the resultant coatings.