Synthesis And Properties Of Polymeric Biomedical Materials Containing Zwitterionic Sulfobetaine Structure

Polymeric materials have been widely used in various biomedical applications, such as artificial hearts, vascular grafts, and pacemaker leads, due to their outstanding mechanical and chemical properties, and moderately good biocompatibility. The interest in biocompatible polymers for medical applications is continuously increasing. "Click" reaction, an advanced synthetic pathway, because of its high efficiency and high tolerance of functional groups and solvents, has become a very powerful tool in the field of polymer science. We have synthesized a series of polymeric biomedical materials containing zwitterionic sulfobetaine structure. These Materials display potential biocompatibility. This dissertation mainly includes four parts:1. A series of novel polyurethanes (PUs) containing zwitterionic sulfobetaine groups have been synthesized using the copper-catalyzed 1,3-dipolar cycloaddition (azide-alkyne "click" reaction). A standard two-step polyaddition method was used to produce the well-defined polyurethanes based on polycarbonatediol (PCDL) and polytetrahydrofuran glycol (PTMEG) with alkyne groups. These PUs containing alkyne units were then efficiently clicked using 3-((2-azidoethyl)dimethylammonio)propane-l-sulfonate (DMPS-N3). These novel PUs were characterized by'H NMR, Fourier transform infrared spectrometer (FTIR), Raman spectroscopy, gel permeation chromatography (GPC), and elemental analysis. And the thermal properties of polycarbonate urethanes were studied by thermogravimetric analysis (TGA), and differential scanning calorimetry (DSC). The results showed that PUs containing zwitterionic sulfobetaine were successfully synthesized by "click" reaction. The TG result shown that polycarbonate urethanes have relatively high thermal stability. The blood compatibilities of the polymers were evaluated by BSA protein adsorption test. The novel segmented polyurethane containing sulfobetaine structure showed improved blood compatibility.This facile "click" reaction provides a useful tool for the development of novel functional polyurethanes for biomedical applications.2. A new zwitterionic PU membrane surface was obtained by a novel three-step graft procedure. The zwitterionic monomer was introduced by cerium-induced graft copolymerization in the presence of N,N'-methylene bisacrylamide (MBAA) as cross-linking agent. Attenuated total reflection Fourier transform infrared spectroscopy (ATR-FTIR) and X-ray photoelectron spectroscopy (XPS) analysis confirmed the MBAA could stimulate zwitterionic monomer grafting onto the membrane surface. Surface properties were also determined by atomic force microscope (AFM) and water contact angle. The hemocompatibility of the modified PU membranes was evaluated by the activated partial thromboplastin time (APTT), thrombin time (TT), prothrombin time (PT) and protein adsorption. The TT and APTT of PU were significantly prolonged by the zwitterionic monomer of sulfobetaine grafting copolymerization. Total protein adsorption on these surfaces was measured in vitro. It was found that all the zwitterionic surfaces have improved resistance to nonspecific protein adsorption The new polyurethane membrane could provide potential biomaterials for tissue engineering scaffolds.3. The zwitterionic monomer of sulfobetaine was graft polymerized onto cellulose membrane (CM) surface in a two-step heterogenous system through surface "click" reaction. Firstly, cellulose membrane was activated with azido groups using a one-pot sequence reaction. Secondly, 3-(diethyl(prop-2-ynyl)ammonio)propane-1-sulfonate (DEPAS) was introduced on cellulose membrane (CM) surface through copper-catalyzed "click" reaction. The CMs were characterized by attenuated total reflectance Fourier transform infrared spectra (ATR-FTIR), X-ray photoelectron spectroscopy (XPS), Raman, scanning electron microscopy (SEM) and atomic force microscope (AFM). It was demonstrated that this approach provided a powerful means for surface immobilization of zwitterionic sulfobetaine groups.4. Surface modification on PVA-co-PE nanofiber membrane was performed with a three-step grafting procedure. In the fist step, PVA-co-PE nanofiber membrane was activated with cyanuric chloride through surface substitute reaction. In the second step, NaN3 and propargyl-amine were grafted onto nanofiber membrane surface by nucleophilic substitute reaction. In the third step, the zwitterionic monomers DEPAS and DMPS-N3 were introduced onto nanofiber membrane surface via "click" reaction. The surface structures were fully characterized with ATR-FTIR, Raman and XPS. Results showed that zwitterionic sulfobetaine functional nanofiber membranes were successfully synthesized. The morphological change was determined by SEM. Results indicated that the nanofiber could keep original morphology in a relatively short time (24 h). The new PVA-co-PE nanofiber membrane could provide potential new biomaterials.