Researches On Polyphenol-Based Multifunctional Coatings For Cardiovascular Materials

Mussel secreted mytilusedulis foot protein (Mefp), which contains the Dopa structure, can firmly adhere onto a variety of materials, such as rock and ship objects. The dirt can form on the inner wall of tea set and is difficult to be removed after repeated use, which is mainly ascribed to the oxidation reactions of tea polyphenols and tea strain. These catechols and polyphenols play a key role in forming effect interface adhesion. Inspired by relative research, the thesis explored the feasibility and research value of polyphenol compounds in surface modification of cardiovascular materials and enriched the design and application of mussel-mimetic adhesive materials.The thesis summarized the cardiovascular disease, vascular stent treatment, and the importance of polyphenols and nitric oxide (NO) in vascular disease. Based on the interface requirements between cardiovascular microenvironment and biomaterials, polyphenol-based multifunctional coatings were prepared. The first part of the thesis comprehensively evaluated the hemocompatibility, endothelial cell (EC) and smooth muscle cell (SMC) compatibility of polydopamine (PDA) coating, along with the investigation of quinones on thermally oxidized PDA coating associated with the influence of subsequent biomolecule immobilization densities. Nest, inspired by mussel adhesive chemistry, phenol/amine cross-linked coatings were prepared and the feasibility of the coatings in introducing of the species and densities of functional groups on material surface. Particularly, by introducing in the coating with cystamine and selenocystamine with the help of Epigallocatechin-3-gallate (EGCG), the evaluation of disulfide and diselenide coating on the function of catalytic decomposition of endogenous NO donors (S-Nitrosothiols, RSNO) to release NO was done. In addition, in view of the roles of catechols in interface adhesion, heparin and poly ethyl enimine (PEI) were modified with catechol moiety and a catechol-modified LBL film was prepared, and a comparative study on the stability of catechol-modified LBL and non-modified LBL was performed. PEI and pyrogallol (PG) LBL film was constructed, and the structure and properties were investigated.The thesis confirmed that, similar with PDA coating, phenol/amine cross-lined coatings could deposit on a variety of material surface, and a larger scope of regulation on the surface functional group densities, species and further biomolecule modification could be achieved via the screening of polyphenol and amine compounds. By evaluation of functional group type and densities on the influence of EC and SMC, surfaces with higher density of phenol hydroxyls could inhibit SMC proliferation to some extent, which provided evidence for the potential applications of polyphenol-containing coatings on cardiovascular material surface. EGCG/cystamine and EGCG/selenocystamine cross-linked coatings were NO-generating materials, which could catalyze the decomposition of RSNO to release NO at a rate about 0.3-4.1×10-10 mol·cm-2·min-1, in or near the level of physiological endothelial cell induced NO release rate ((0.5-4×10-10 mol·cm-2·min-1). Using the carboxyls or amines in heparin or PEI molecules, catechol moieties were successfully modified on heparin or PEI via EDC/NHS method, and the LBL film prepared with catechol modified heparin and PEI presented significantly enhanced stability in PBS environment, compared with non-modified LBL film. Moreover, the constructed PEI/PG LBL film was based on PEI backbone and formed a solidified liquid layer. The significant ability of inhibit platelet adhesion and activation was found on the outer layer surface with higher density of PEI. The results obtained with the systematic evaluation of such coating could provide a novel thinking in the design and preparation of anti-coagulant materials.In conclusion, inspired by mussel adhesive proteins, polyphenol-based multifunctional coatings were prepared in this thesis, focusing on the special requirements of cell or blood compatibility on the surface of cardiovascular materials. The coating preparation method is simple and with the control of parameters, coatings or further modifications in the regulation of blood or cell compatibility is feasible. This thesis demonstrated the feasible and importance of polyphenol-based coatings on cardiovascular material surface modification and proposed new approaches and platform in achieving idea interface demands between biomaterials and cardiovascular environment.