Imitation Of The Membrane Structure Of The Polymer Synthesis And Its Application

With the rapid development of modern medical science, various kinds of minimally invasive interventional medical devices, such as catheters, vessel stents, sensors, heart aids and the like, have been widely applied to medical application, and have greatly enriched the treatment means of modern medicine clinics. However, when these devices come into contact with living organisms, thrombus formation, infection and other unfavorable immune responses occur sooner or later, which cause discomfort to the patient and increase the cost and, in some cases, means that more surgery is required. Biocompatibility, including blood compatibility and tissue compatibility, is the most important property that any useful biomedical material must possess. Unfortunately, it is rare that a biomaterial with good bulk properties also exhibits suitable biocompatibility. It is the surface of a biomaterial that enters into contact with living tissues when the biomaterial is placed in the body. Therefore, surface modification is a key process for biomaterials as well as devices for clinical applications. About 1980s, one of the most attractive methods of surface modification for biomaterials, "biomimicry", was proposed by Nakabayashi with his coworkers and Chapman with his coworkers. This concept involves reproducing the surface properties of the thromboresistant surfaces of blood cell membranes. This is achieved by use of chemical entities that having the structure of phosphorylcholine (PC) group. The hydrophilic zwitterionic polar PC-group is the major lipid headgroup of the extracellular lipid bilayer, which is the cause of the extracellular surfaces of blood cell membranes thromboresist. The research on PC containing polymers has been expanding rapidly in various fields, such as surface modification of biomaterials, drug delivery systems, cosmetics, and so on.In this dissertation, a novel crosslinkable terpolymer coating material bearing phosphorylcholine functionality was prepared. A method on adjustment and immobilization of biomimetic structure of surface coating was proposed and applied on surface modification in order to get a stable hydrophilic haemocompatible surface/interface. The main works are as follows.Phosphorylcholine dichloride, a useful reactive compound, was synthesized directly from phosphoryl chloride and choline chloride under anhydrous condition in a single step reaction, and was applied to modify the surface of glass. The synthetic conditions were studied by a modified potentiometric titration method here. Dynamic contact angle (DCA) measurement and X-ray photoelectron spectroscopy (XPS) analysis confirmed that a biomimetic surface was obtained successfully by grafting phosphorylcholine dichloride on glass, which provides another new way for surface modification of biomaterials. In order to study the synthetic conditions and the quantitative analysis of phosphorylcholine dichloride, the conventional potentiometric titration method on phosphoric acid was modified here. The modified potentiometric titration method is more accurate and rapid at analyzing the composition of phosphate mixture, and also helpful for searching for better synthetic conditions.2-methacryloyloxyethyl phosphorylcholine (MPC) is an important monomer. The synthetic route of MPC was studied here. The experimental apparatus of traditional synthetic route was improved here and the yield increased greatly in each step. Furthermore, two new synthetic routes of MPC were explored. The two new routes were proved feasible through the elemental analysis, IR and ~1H NMR of MPC homopolymer and copolymer. However, the difficulty in the purification of MPC obtained from the new routes still needs more effort.A novel crosslinkable phosphorylcholine based terpolymer PMST was synthesized by the radical polymerization from three kinds of monomers including the biomimetic monomer MPC, the hydrophobic monomer stearyl methacrylate (SMA), and the crosslinkable monomer trimethoxysilylpropyl methacrylate (TSMA). The random terpolymer PMST was obtained through monomer-starved technique. PMST and a series of reference polymers were characterized by determination of ~1H NMR, attenuated total reflection infrared spectroscopy (ATR-IR), differential scanning calorimeter (DSC), critical micelle concentration (CMC), matrix assisted laser desorption/ionization time-of-flight mass spectrometry (MALDI-TOF MS). PMST with 20mol% TSMA in the terpolymer was chosen to prepare biomimetic crosslinkable coating. PMST was coated onto cover glass by dip-coating or Langmuir-Blodgett (LB) technique. The research was mainly focused on the surface structure and property of dip-coated film. The coating was treated in different methods in order to get a biomimetic interface structure. The structure after adjusting was fixed by crosslinking of the trimethoxysilylpropyl groups. DCA, atomic force microscope (AFM) and XPS were used to study the hydrophilicity, surface morphology, and surface elemental composition of coating, respectively. It was found that the hydrophilic surface was different from the hydrophobic one on physical and chemical properties. The platelet adhesion and protein adsorption experiments show that, the blood compatibility of the surface modified with PMST20 coating was excellent, and the hydrophilic PMST20 surface was better. The method on adjustment and immobilization of biomimetic structure of surface coating here could improve biocompatibility of the biomimetic polymers greatly, and also provide theoretical base for improving the application performance for biomedical materials and devices. In addition, PMST could be a novel material to prepare stable drug delivery polymeric nano-micelles as it was a crosslinkable amphiphilic polymer with a lower CMC.