Functionalization Of Polymer Film By SET-LRP&Click-chemistry For Biomedical Applications

The synthetic polycations are ideal candidates as antimicrobial agents, becausethey resemble natural antimicrobial peptides, but to render hemocompatibility to thesematerials is a great challenge. Herein, we used2-(tert-butyl-aminoethyl) methacrylate(TBAEMA), to synthesize its homopolymer and pegylated random and diblockcopolymers with polyethyleneglycol methacrylate (PEGMA, Mn=360Da) by single-electron transfer living radical polymerization (SET-LRP). In the second step, thesecondary amino groups in the precursor polymers were quaternized with iodomethaneand bromohexane, to obtain three series of quaternized polymers. The antimicrobialproperties of these quaternized polymers were evaluated against E. coli, by studyingthe minimum inhibitory concentrations (MICs) which ranged between32-200mg/Land showed higher values for the quaternized random than the diblock copolymers. Inaddition to, we have also demonstrated the grafting of these polycations ontopolycarbonate urethane film surfaces, which showed good killing efficacy against E.coli. Furthermore, the hemolysis of these materials were investigated against humanred blood cells, which indicated that except the quaternized homopolymers that showedhighest hemolysis, all other amphiphilic polycations exhibited very low hemolyticactivity. Therefore our designed materials with controlled structures and functionality,synthesized from cheaply available resources could serve as useful agents in the fieldof biomedicines and implantable materials.Moreover, the polyurethane (PCU) and zwitterionic polynorbornene basedelastomeric cross-linked film as cells growth substrate was prepared using thioleneclick-chemistry and crosslinking reaction. Firstly amine functionality was introducedinto polynorbornene (poly(NSulfoZI) having functionalizable double bonds by treatingwith L-cysteine using photo-initiated thiolene click-reaction, followed by controlledreaction with PCU-solution in the presence of hexamethylenediisocynate homopolymer(HHDI) cross-linker. The obtained films possessed improved tensile strength of (14-20MPa) and initial modulus (8-14MPa), in comparison to12±4MPa and3±1MParespectively, for blank film. All of these films including blank one, showed highbreaking strain (b740-900%), except with a highest zwitterion content of28%(b470±80%). The biodegradability of these materials was enhanced, tested in PBS for5weeks as against blank PCU. The blank PCU-film surface could also be modified underthe aforementioned condition using L-cysteine or β-marcaptoethanol as thiol-agents. The cytocompatibility of all these materials investigated by MTT assay, growth andproliferation of model endothelial cells EA.hy926for1,3and7day/s, showedsignificant biocompatibility. The convenient route and the unique characteristic in asingle material is the main focus of this work.Furthermore, the PCU elastomer film surface was tailored to affect the rapidendothelialization and inhibition of smooth muscle cells and blood platelets adhesion.In the first step PCU surface was grafted with hydrophilic polymer brushes,polyethylene glycol methacrylate (PEGMA) using single-electron transfer livingradical polymerization (SET-LRP), which was subsequently grafted with an activemonomer pentafluorophenyl methacrylate (PFMA) by a second SET-LRP to createblock and grafted structures. After postpolymerization modification of the PPFMAchains with allyl amine, the pendant allyl groups were functionalized with shortpeptides sequence, Cys-Ala-Gly (CAG) using photo-initiated thiolene click-chemistry.The film surface at different stages of modification was confirmed by XPS and watercontact angle analysis. The immobilized CAG concentration was effective up to10-19pm/cm2. The different functionalized surfaces suppressed platelets adhesion on a directcontact with the whole blood. The relative adhesion of endothelial cells (EA.hy926)(ECs) and human umbilical arterial smooth muscle cells (HUASMCs) was monitoredat time intervals1,3and7day/s. Results indicated that using this convenient route tosurface-anchor ECs selective targeting ligand, the created platform were useful in rapidendothelialization and could serve as a tissue engineering elastomeric substrate.