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Biomedical subjects

S Nakahama

Publications and source records attributed to S Nakahama.

9 recordsLinked to original sources

Prevention of changes in platelet cytoplasmic free calcium levels by interaction with 2-hydroxyethyl methacrylate/styrene block copolymer surfaces.

Changes in platelet cytoplasmic free calcium levels were investigated in contact with cast film surfaces of a block copolymer containing 2-hydroxyethyl methacrylate (HEMA) and styrene (St) (0.5 mole fraction HEMA). These copolymer surfaces demonstrate microdomain alternating lamellae structures composed of hydrophilic HEMA domains (5 nm width) and hydrophobic St domains (20 nm width). The results were compared with those obtained from platelets contacting a random copolymer of HEMA-St (0.5 mole fraction HEMA) and from homopolymers of polystyrene (PSt) and poly(2-hydroxyethyl methacrylate) (PHEMA). Cytoplasmic free calcium levels in platelets contacting the microdomain structured surfaces of the HEMA-St block copolymer remained relatively constant in contrast to the significant increases observed for the radically prepared HEMA-St copolymer, PSt, and PHEMA surfaces. Adhering platelets were stimulated by exogenously introduced thrombin and calcium ionophore A23187 20 min after platelet adherence to the polymer surfaces. Only platelets on the block copolymer surfaces showed active metabolic responses. These results suggest that adhering platelets on the microdomain structured surfaces maintain high sensitivities to external stimulation due to an intrinsic strong inhibition of platelet functional changes induced by surface contact.

Blood Platelets↗

Surface characterization of 2-hydroxyethyl methacrylate/styrene copolymers by angle-dependent X-ray photoelectron spectroscopy and static secondary ion mass spectrometry.

The surface composition and structure of three structurally distinct amphiphilic copolymers of 2-hydroxyethyl methacrylate (HEMA) and styrene have been examined with angle-dependent X-ray photoelectron spectroscopy (XPS) and static secondary ion mass spectrometry (SIMS). The phase-separated block copolymer made by anionic living polymerization, HSH-A50, showed significant surface enrichment of styrene. The outermost 2-3 A appeared to be approximately 100% styrene, with the styrene concentration decreasing to its bulk value at a depth of approximately 50 A from the surface. However, HEMA was detected in the outer 20 A of this copolymer. The presence of HEMA in the surface region implies this copolymer may undergo significant restructuring when hydrated in a hydrophilic environment (as opposed to the hydrophobic environment in which the sample was prepared and analyzed). The phase-separated block copolymer made by telechelic coupling of free radical polymerized functionalized oligomers, HSH-B60, showed only slight styrene enrichment at the surface. Both HEMA and styrene were detected at all sampling depths, including the outermost surface layer, consistent with the presence of discrete HEMA and styrene domains at the copolymer surface. Since both components are already present at the surface under hydrophobic conditions, the degree of restructuring this copolymer may undergo upon hydration should be minor. The random HEMA--styrene copolymer made by conventional free radical initiation techniques, HS-RAN50, had a surface composition that was similar to the bulk composition and independent of depth, as expected for a homogeneously mixed copolymer film.

Biocompatible Materials↗

In vivo protein adsorption on polymers: visualization of adsorbed proteins on vascular implants in dogs.

The absorption of plasma proteins is an important event at the blood-material interface, and strongly affects subsequent cellular interaction and thrombus formation. Although considerable efforts have been expended to elucidate the mechanism of protein adsorption and the role of absorbed protein layer at the blood-material interface, there has been little knowledge of how the initial adsorbed proteins are maintained or changed in a time-variant process in in vivo long-term implantation. In this study, we described detailed analyses concerning the characterization of adsorbed proteins on HEMA--styrene block copolymer surfaces (HEMA-st) and poly(ethylene oxide) (PEO) grafted Biomer (B-PEO4K) for in vivo long-term canine vascular graft implants as well as in vitro short-term experiments. Biomer vascular grafts (6 mm I.D., 7 cm in length) were fabricated by a dip coating and the luminal surface was modified with PEO grafting, HEMA-st coating, or Biomer coating (control). These surface modified grafts were recirculated for different time intervals (5, 15, 30, 60 and 120 min) using citrated canine whole blood. The grafts were then implanted in the abdominal aortas of dogs and evaluated for graft patency and protein adsorption. The adsorbed proteins (albumin, IgG and fibrinogen) were quantified using an in situ radioimmunoassay. Surface protein layer thickness was measured by transmission electron microscopy (TEM). Visualization of absorbed plasma proteins (albumin, IgG and fibrinogen) was performed with TEM using an immunoperoxidase double antibody technique. In in vitro recirculation systems, albumin and IgG showed similar Langmuir type pattern onto all test surfaces. On B-PEO4K surfaces, fibrinogen adsorption kinetics demonstrated 'Vroman effect'. The Biomer and B-PEO4K grafts occluded within 1 month, while HEMA-st grafts were patent for over 3 months. Biomer and B-PEO4K showed thick multilayers of adsorbed proteins, and the thickness increased with implantation periods and the composition altered with time. In contrast, HEMA-st showed a monolayer-like adsorbed protein pattern, and the composition and thickness were consistent regardless of implantation time including in vitro short-time experiments, which may attribute to less conformational change of adsorbed proteins on HEMA-st surfaces. In terms of nonthrombogenicity, the stable monolayer-like adsorbed protein layer on HEMA-st surfaces exhibited improved blood compatibility over thick multilayered adsorbed proteins on Biomer and B-PEO4K surfaces.

Adsorption↗

A new amphiphilic block co-polymer with improved elastomeric properties for application in various medical devices.

The authors have demonstrated that an amphiphilic block co-polymer composed of 2-hydroxyethyl methacrylate (HEMA) and styrene (HEMA-st) showed excellent blood compatibility in in vitro, ex vivo, and in vivo experiments. The poor elastomeric properties of HEMA-st, however, have been an obstacle to its wider application in medical devices. To improve the mechanical properties of HEMA-st, the authors have developed a new amphiphilic block co-polymer composed of HEMA and octylstyrene (HEMA-oct). The size and morphology of the microdomain structures of HEMA-oct observed by transmission electron microscopy were similar to those of HEMA-st. Kink resistance tests showed improved elastomeric properties of HEMA-oct over HEMA-st. The blood compatibility of HEMA-oct was evaluated using an in vitro flow cell system combined with an epifluorescent video microscope, in which real time platelet adhesion and activation in whole blood can be observed and quantified, and ex vivo rabbit A-A shunt experiments. HEMA-st and a polyurethane (Pellethane 2363-80AE) were used for comparison. In a flow cell system, both HEMA-st and HEMA-oct showed minimal platelet coverage on the surfaces and less platelet activation as measured by beta-thromboglobulin (beta-TG), whereas Pellethane showed a considerable amount of platelet coverage with high beta-TG production. A-A shunt occlusion times were 309 +/- 31.2 min for HEMA-st, 251 +/- 47.7 min for HEMA-oct, and 30 +/- 3.4 min for Pellethane.(ABSTRACT TRUNCATED AT 250 WORDS)

Adult↗