| Device-associated infections(DAIs)have become the most common infections in hospitals,which seriously threaten the health of patients.The construction of antibacterial surface based on polymers is a feasible solution to DAIs.At present it is still a great challenge to improve both antifouling property and bactericidal activity of polymer coatings.Synthetic polypeptides have the similar structure and antibacterial properties of AMPs and unique secondary structures,such as β-folded conformation,so they have attracted much attention in the field of antibacterial polymers.Previous studies have shown that hydrophilic polymer materials such as polyethylene glycol(PEG)have good antifouling properties.The topological structure of annular hydrophilic chain segment is beneficial to improve the antifouling performance.Increasing the local charge density of cationic chain segment is able to enhance the bactericidal activity of antibacterial polymers.Such a structure is expected to enhance both bactericidal activity and antifouling property of coatings.In this paper,we prepared several block copolymers based on antifouling polyethylene glycol(PEG)and bactericidal polypeptides.We use single-chain nanoparticles(SCNPs)by intramolecular crosslinking or the intermolecular hydrogen bonding interaction(β-folded conformation)to build circular PEG chain and improve the local charge density of cationic segment at the same time,aiming to obtain multifunctional antibacterial surfaces,providing new materials and methods for DAIs.The main research contents are as follows:In Part 1,we designed and prepared triblock copolymer LP-KF coating and single-chain nanoparticle NP-KF coating based on PEG and cationic polypeptides.NP-KF was prepared from LP-KF by intramolecular crosslinking.The results of GPC,AFM and DLS showed that the particle size of the polymer decreased after crosslinking,confirming intramolecular rather than intermolecular crosslinking.The coating was prepared by PDA-assisted deposition.The molecular structure,thickness,roughness and hydrophilicity of the coating were characterized by XPS,FTIR,AFM and WCA.Compared with linear copolymer LPKF,NP-KF showed enhanced bactericidal activity and antifouling performance,and the killing activity of NP-KF on Staphylococcus aureus and Escherichia coli was>99.9%,and the protein adsorption and bacterial adhesion were significantly reduced,and the cytotoxicity was low.In vivo experiment results showed that NP-KF coating has significant anti-infection effect and good histocompatibility.In Part 2,two self-deposited polypeptides with different conformations were prepared using L-glutamate monomer(BLG-NCA)or L-Serine monomer(Ser-NCA),lysine monomer(Boc-Lys-NCA)and dopamine monomer(Dopa-NCA).Namely,α-helical P(BLG-Lys-Dopa)and β-folded P(Ser-lys-Dopa).Uniform polypeptide coating was prepared by dip-coating.In vitro experiments,P(Ser-Lys-Dopa)showed higher bactericidal activity and anti-adhesion than P(BLG-Lys-Dopa).In addition,P(Ser-Lys-Dopa)has a low hemolysis rate(<0.9%),and the cell coverage of NIH 3T3 fibroblasts reached 72%after three days on P(Ser-Lys-Dopa)coating,indicating good biocompatibility. |
