Novel photoreactive phospholipid polymers for preparing a stable biocompatible surface with a smart process

Abstract

Event Abstract Back to Event Novel photoreactive phospholipid polymers for preparing a stable biocompatible surface with a smart process Tomozumi Noda1*, Masaru Matsuda1*, Nobuyuki Sakamoto1*, Shigeru Kitano1*, Yuuki Inoue2*, Kyoko Fukazawa2* and Kazuhiko Ishihara2* 1 NOF Corporation, Life Sciences Products Division, Japan 2 The University of Tokyo, Department of Materials Engineering, School of Engineering, Japan Introduction: 2-Methacryloyloxyethyl phosphorylcholine (MPC) [1] polymers have been widely applied to some medical devices, including implantable blood pumps, cardiovascular stents and other medical goods. Stabilization of the MPC polymer layer on the substrate is essential issue to solve to have conventional surface treatment. In this study, in order to react the MPC polymer layer to the substrate, we have newly synthesized photoreactive MPC polymers to modify the plastic surface, and evaluated fundamental properties regarding biocompatibility, that is, protein adsorption and cell adhesion. By using these photoreactive MPC polymers, surface treatment is conducted very easy way, such as, coating of the MPC polymer by solvent dipping and after that irradiation light. Materials and Methods: Two types of photoreactive MPC polymers bearing n-butyl methacrylate (BMA) and benzophenone group or phenylazide group were synthesized in a conventional free-radical copolymerization. The presence of benzophenone group (7.20-8.00 ppm ) or phenylazide group (7.10-7.35 ppm and 7.90-8.25ppm) was confirmed by Proton NMR. Each MPC polymer was used for surface modification on various substrates, such as polyethylene and polystyrene, by dip or cast coating, and following the photoirradiation of UV light at 254nm for 7 min. After photoirradiation, all substrates were soaked in ethanol more than 16 h to evaluate reactivity of MPC polymers. The hydrophilic characteristics of the substrates modified with photoreactive MPC polymers were evaluated contact angle measurement by air under water. Then the 96-well polystyrene plates treated with photoreactive MPC polymers were used for examining protein adsorption using peroxidase conjugated antibody and cell adhesion of NIH3T3 cells. Result: Novel photoreactive MPC polymers possessing MPC unit, BMA unit and photoreactive groups were successfully synthesized. The monomer unit fraction of the MPC unit was 60 mol %, BMA unit was 30 mol % and photoreactive group was about 10 mol %. The photoreactive groups were confirmed by 1H-NMR. These polymers can be dissolved in alcohol. Regardless of the kind of the MPC polymers, the treatment resulted in high contact angles of air on the surfaces under water (100 o to 140 o). In addition, protein adsorption and cell adhesion were suppressed. On the other hand, those of the substrates without photoirradiation were equivalent to non-treated substrates in all examinations. Discussion: The substrates treated with the MPC polymers coating and photoirradiation were demonstrated good hydrophilicity even after washing process with ethanol. At this substrate, we observed reduced protein adsorption and cell adhesion. These are one of the fundamental characteristics for making blood-contacting medical devices and implantable devices. These results were due to formation of covalent bonds between the MPC polymers and the substrates and stable surface modification layer was constructed. Conclusion: We developed a smart process to obtain stable and biocompatible surface using photoreactive MPC polymers. The surfaces of various substrates modified with the photoreactive MPC polymer showed super-hydrophilic character, reduction of protein adsorption and inhibition of cell adhesion. Also, the photoreaction with the MPC polymer will be applied to treat a microspace of the substrate. Thus, this excellent anti-biofouling nature will be important to make biocompatible medical devices and biodevices. This research was supported by S-innovation from Japan Agency for Medical Research and Development (AMED)