Shigemasa Osaki

Cell attachment and biocompatibility of polytetrafluoroethylene (PTFE) treated with glow-discharge plasma of mixed ammonia and oxygen

The plasma generated from a gas mixture of NH3 plus O2 (NH3 + O2) has been used to impart unique chemical and biological characteristics to polytetrafluoroethylene (PTFE). PTFE treated with NH3 + O2 plasma was physiochemically distinct from surfaces treated with plasma of either NH3 or O2 alone, as determined by electron spectroscopy for chemical analysis (ESCA). The contact angle analysis revealed that the PTFE surfaces became less hydrophobic after plasma treatments. ESCA results indicate the presence of oxygen-containing groups and nitrogen-containing groups at the plasma-treated surfaces. PTFE treated with NH3 + O2 plasma resisted the attachment of platelets and leukocytes in a manner similar to untreated PTFE; however, the attachment of bovine aorta endothelial cells was substantially increased. Once attached, these cells grew to confluency. The increased endothelial cell attachment was higher than that observed following plasma treatment with each gas used separately, which could be attributed to the considerable amount of CF(OR)2-CF2 formed on the NH3 + O2 plasma-treated PTFE surface. At 14 days after subcutaneous implantation in rats, the PTFE wafers treated with NH3 + O2 plasma demonstrated less encapsulation and lower levels of inflammatory cells compared to controls. Collectively, the results suggest that NH3 + O2 plasma treatment imparts a unique character to PTFE and could be useful in certain in vivo applications.

Controlled Drug Release through a Plasma Polymerized Tetramethylcyclo-tetrasiloxane Coating Barrier

A plasma polymerized tetramethylcyclo-tetrasiloxane (TMCTS) coating was deposited onto a metallic biomaterial, 316 stainless steel, to control the release rate of drugs, including daunomycin, rapamycin and NPC-15199 (N-(9-fluorenylmethoxy-carbonyl)-leucine), from the substrate surface. The plasma-state polymerized TMCTS thin film was deposited in a vacuum plasma reactor operated at a radio-frequency of 13.56 MHz, and was highly adhesive to the stainless steel, providing a smooth and hard coating layer for drugs coated on the substrate. To investigate the influence of plasma coating thickness on the drug diffusion profile, coatings were deposited at various time lengths from 20 s to 6 min, depending on the type of drug. Atomic force spectroscopy (AFM) was utilized to characterize coating thickness. Drug elution was measured using a spectrophotometer or high-performance liquid chromatography (HPLC) system. The experimental results indicate that plasma polymerized TMCTS can be used as an over-coating to control drug elution at the desired release rate. The drug-release rate was also found to be dependent on the molecular weight of the drug with plasma coating barrier on top of it. The in vitro cytotoxicity test result suggested that the TMCTS plasma coatings did not produce a cytotoxic response to mammalian cells. The non-cytotoxicity of TMCTS coating plus its high thrombo-resistance and biocompatibility are very beneficial to drug-eluting devices that contact blood.

Radiolabeling brachytherapy sources with re‐188 through chelating microfilms: Stents

Rhenium-188 (Re-188, T(1/2) = 17 h) emits beta particles (E(max) = 2. 12 MeV) having an ideal range for intravascular brachytherapy and certain cancer brachytherapies. Re-188 was attached to metal wafers and stents via a chelating microfilm, and these brachytherapy sources characterized in vitro and in vivo. To prepare the sources, a siloxane film containing reactive amines was plasma deposited on the metal, a chelating microfilm conjugated to the amines, and the chelating microfilm used to attach Re-188. Re-188 was selectively bound to materials coated with the chelating microfilm. Binding correlated with the amount of radionuclide used. Wafers (1 cm(2)) bound up to 62.9 MBq (1.7 mCi) of Re-188 with yields generally near 30%. Stents bound up to 26.6 MBq (720 microCi). Typically, stents were labeled to bind 4-12 MBq and deposit 10-30 Gy at 2 mm in the arterial wall. In phantom studies, the longer nitinol stents deposited doses of 2.3 Gy/MBq (0.085 Gy/microCi), while shorter stainless steel stents deposited 4.62 Gy/MBq (0.171 Gy/microCi). After placement in arteries of pigs, only the Re-188-stents were detected by scintigraphy at times up to 24 h. Scintigraphy did not detect activity in other organs. Blood sampling (0.1-24 h) detected maximum radioactivity (up to 388 cpm/mL/100micro Ci) at 6 h. We conclude that on-demand radiolabeling of stents and other brachytherapy sources with Re-188 can be performed routinely.

Preparation of a Plasma Polymerized Tetramethylhydrocyclotetrasiloxane Membrane on Microporous Hollow Fibers

A variety of polypropylene microporous hollow fibers are widely used in oxygenator devices. The hollow fiber serves as an interface support between gas and liquid phases. There are two potential problems associated with using microporous hollow fibers in an oxygenator: (a) plasma leakage and, (b) the need for systemic heparin to prevent thrombus formation on the fibers during in vivo usage1–2 Microporous hollow fiber coated with plasma polymerized 1,3,5,7-tetramethylhyd rocyclotet rasil oxane membrane, HydroSilox®, can prevent plasma leakage and provide an anti-thrombogenic surface.

Improvement of Surface Lubricity of Polymers and Metals by a Glow-Discharge Plasma Cross-Linking Process

A plasma cross-linking process was employed to improve the surface lubricity of different types of biomaterials, including stainless steel (SS), nitinol, polyethylene and nylon. To investigate the influence of monomers containing double bonds on top-layer cross-linking of poly(ethylene oxide) compound (PEOC), five different monomers, N-trimethylsilyl-allylamine (TMSAA), ethylene, propylene, allyl alcohol and ethane, were used in the study to produce a cross-linked coating layer on sample surfaces. Before the plasma cross-linking, samples underwent plasma treatment followed by wet chemical coating. The plasma treatment consists of plasma etching in NH3/O2, Tetramethylcyclo-tetrasiloxane (TMCTS) coating and TMSAA grafting. The wet coating process includes dip-coating in a solution of poly(oxyethylene)-compound bis(1-hydroxy-benzotriazolyl carbonate) (HPEOC), then dip-coating in a solution of PEOC. By application of plasma processing, HPEOC and PEOC wet coating to sample surfaces, the lubricity was increased by 83% compared to clean samples. The plasmas of TMSAA, ethylene, propylene and allyl alcohol, all containing a C=C double bond, produced a cross-linking layer on the PEOC surface. Consequently the surface lubricity was improved by 20% to 37% in comparison to no cross-linking. The favorable condition for plasma cross-linking was found to be high power and long time. Ethane plasma also reduced the pulling force although it has no double bond in the molecular structure, which indicated a thin plasma coating from saturated hydrocarbons deposited on HPEOC or PEOC surfaces could also cause cross-linking and improve lubricity. It was found that the TMSAA cross-linking also worked on HPEOC and HEPOC/PEOC, even though the prior plasma coating process was skipped.