Preparation And Blood Compatibility Of Heparin-mimicking Polymer Modified Material Surfaces

Blood compatibility is the forever topic to design biomaterials.Heparin-mimicking polymers modified materials show good hemocompatibility,which is comparable to heparin-modified materials.Despite a lot of work in this area,there are still no clear rules or extensive structure-property relationships on how the structural parameters relate to resultant biological properties.Accurate synthesis of heparin-mimicking polymer on the surface of the material is not easy,especially considering the effects of multiple chemical structural factors(including saccharide-,sulfonate and carboxyl units)on the biological properties,which often increase the complexity and difficulty of the synthesis step.Therefore,it is of great significance to develop a facile strategy to synthesize heparin-like polymers on the material surfaces with controllable composition,so as to further clarify the relationship between chemical composition and biological properties of heparin-mimicking polymers.In this thesis,heparin was conceptualized as consisting of three major structural elements: saccharide-,sulfonate and carboxyl-containing units,and based on this concept,a series of materials modified by heparin-mimicking polymer were designed.The influence of the content,and combining form of the building units on the biological functions of the modified materials was investigated.Through regulating the composition of the building units on the surface,we seek to develop a multifunctional surface with anticoagulant properties,ability of endothelialization and inhibiting the hyperplasia of smooth muscle cells.The main study content is as follows.(1)Heparin-mimicking polymer modified surfaces with adjustable ratio of saccharide and sulfonate groups were prepared and antithrombogenic properties of the modified surfaces were investigated.Saccharide groups(MAG),and sodium 4-vinylbenzenesulfonate(SS)containing sulfonate groups,were graft-polymerized on vinyl-functionalized polyurethane(PU)surfaces by free radical polymerization.The saccharide and sulfonate contents are tunable by regulating the feed ratio of the monomers.Homopolymer-grafted materials,containing only sulfonate or saccharide groups,showed different effects on cell-surface interactions including platelet adhesion,adhesion and proliferation of vascular endothelial cells,and adhesion and proliferation of smooth muscle cells.Among the copolymer-grafted materials,the optimum anticoagulant surface was obtained at a 1:2 ratio of saccharide to sulfonate units(material designated as PU-PS1M1).This material showed the longest plasma clotting time,the lowest platelet and human umbilical vein smooth muscle cell density and the highest human umbilical vein endothelial cell density.(2)The effect of carboxyl groups on antithrombogenic properties of heparinmimicking polymer modified surfaces was investigated.MAG,SS and acrylic acid(AA)were chosen as monomers,then a series of well-defined homopolymers and copolymers with a narrow molecular weight distribution were synthesized by a reversible addition-fragmentation transfer(RAFT)polymerization method.The polymers were treated with ethanolamine and self-assembly of the resultant the thiol-containing polymers were performed on the gold-coated surface.The surface containing polymer PS1M1(MAG/SS = 1/1)significantly promoted endothelial cells proliferation and inhibited smooth muscle cells proliferation.The Au-PAA surface,containing only poly(acrylic acid)(PAA)inhibited proliferation of both endothelial cells and smooth muscle cells.When the molar ratio of PS1M1 and PAA is 1:1,the modified material(Au-PSM/PAA-2)showed the property of promoting adhesion and proliferation of endothelial cells,while inhibiting the adhesion and proliferation of smooth muscle cells.Compared with the modified surface containing only PS1M1,Au-PSM/PAA-2 showed stronger promoting effect on adhesion and proliferation of endothelial cells,whereas there was no significant difference on the inhibitory effect on smooth muscle cells.In conclusion,by regulating the composition of saccharide-,sulfonate and carboxyl units in polymer,the surface of the modified material can achieve an organic balance in anticoagulant performance,endothelialization and smooth muscle cells proliferation.This work of will enrich the basic research theory of the relationship between structure of heparin-mimicking polymer and biological properties,and at the same time provide new ideas for the multi-functional design of hemocompatibility materials.