Kazuhisa Senshu

In vitro studies of immobilized heparin and sulfonated polyurethane using epifluorescent video microscopy.

In situ surface modification techniques to improve the blood compatibility of blood contacting surfaces of medical devices have been developed by the authors. The techniques include heparin immobilization and sulfonated polymer grafting onto a polyurethane (PU) surface by using either ozone oxidation or photo reaction. These modified PUs were evaluated using an epifluorescent video microscope combined with a parallel plate flow cell. The epifluorescent video microscope system measured the amount of platelet coverage on the PU surfaces using whole human blood containing mepacrine labeled platelets perfused at a wall shear rate of 100 sec-1 for 20 min. Platelet activation and complement activation were also measured. Both immobilized heparin and sulfonated PUs showed significantly lower levels of platelet adhesion than the control PU. The platelet activation levels of these modified PUs also correspond to the results of the platelet adhesion. As for complement activation, heparin the immobilized surface showed the least complement activation, while sulfonated PU and the control PU showed higher levels of complement activation. In situ surface modification techniques, which use either ozone oxidation or photo reaction, are useful in a variety of medical devices even of a complex design, such as membrane oxygenators or artificial hearts.

Polyether-segmented nylon hemodialysis membrane. VI. Effect of polyether segment on morphology and surface structure of membrane

Amorphous nylon, poly(iminoisophthaloyliminomethylene-1,3-cyclohexylenemethylene) (NyBI) and poly(ethylene oxide) (PEO)-segmented NyBI (PEO–NyBI) membranes were prepared by a phase-inversion method using water/dimethyl sulfoxide (DMSO) mixtures as coagulants. The influence of the PEO segment and coagulant compositions on the morphology of the membranes was investigated. The cloud-point curves in the polymer/DMSO/water ternary system showed that PEO–NyBI and NyBI had the same coagulation processes, that is, instantaneous liquid–liquid phase separation occurred, resulting in a fingerlike structure in the cross section of the membranes. The membrane morphologies observed under a scanning electron microscope (SEM) agreed with the prediction. The PEO segment had little or no effect on the membrane morphologies which were prepared in the coagulants with a low DMSO concentration, and it promoted the change of the phase-separation style from the instantaneous to the delayed one in the case of the DMSO-rich coagulant. The PEO segment, however, significantly influenced the ultrafiltration rate. Additionally, the relationship between the surface composition of the PEO–NyBI membrane and the coagulation condition was also investigated by use of electron spectroscopy for chemical analysis (ESCA) and static secondary ion mass spectrometry (SSIMS). A small enrichment of the PEO segment at the top surface of the membranes was observed with the increase of the DMSO concentration in the coagulant.

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)

Comparative blood compatibility of polyether vs polycarbonate urethanes by epifluorescent video microscopy.

The segmented polyether urethanes (PEUs) have been used in implantable medical devices due to excellent mechanical properties, acceptable blood compatibility, and good biostability. However, recent studies demonstrate that the polyether soft segment of PEU is susceptible to oxidative degradation in vivo due to scission of the polyether group. Recently, polycarbonate urethanes (PCUs) having no ether linkage in the soft segment have been developed, and show improved stability against oxidative degradation over PEUs. The current study evaluates blood compatibility of these PCUs in comparison with PEUs using epifluorescent video microscopy (EVM) combined with a parallel plate flow cell. The authors selected two PCUs, Corethane 80A (Corvita Corporation, Miami, FL) and PCU(1560), and two PEUs, Pellethene 2363–80AE (Dow Chemical Japan, Tokyo, Japan) and Tecoflex EG80A (Thermedics, Inc., Woburn, MA), all of which have similar hard segment compositions (MDI or HMDI:1,4-butanedio(BD)) and the same hardness of 80A. The EVM measured the amount of platelet coverage on the surfaces using human whole blood perfased at a wall shear rate of 100/sec for 20 min. Complement activation (C3a) also was measured. Both PEUs, especially Pellethane, showed significantly higher platelet adhesion than the PCUs (p < 0.05). There were no significant differences in platelet adhesion between the two PCUs. As for C3a measurements, Tecoflex showed higher complement activation than the others. Based on these results, it is recommended that PEUs should be replaced by ether free PCUs for use in implantable blood contacting devices such as artificial hearts and pacemaker lead insulators. ASAIO Journal 1997; 43:M500-M504.

In Vitro Evaluation of Six Different Segmented Polyurethanes and HEMA/St Block Copolymer Using Epifluorescent Video Microscopy

We evaluated the blood compatibility of six different segmented polyurethanes (PU), including five polyether-PUs and one polyurethane-urea (PUU), with poly (tetramethylene etherglycol) (PTMG) as the soft segment, using epifluorescent video microscopy (EVM) combined with a parallel plate flow chamber. An amphiphilic block copolymer composed of 2-hydroxyethyl methacrylate (HEMA) and styrene (St) (HEMA/St), which has already been proven to be an excellent nonthrombogenic polymer, was used as a control. The EVM system measured the platelet adhesion on the surfaces of the PUs, using whole human blood containing Mepacrine-labeled platelets perfused at a wall shear rate of 200 s−1 at 1-min intervals for a period of 20 min. Platelet activation (β-thromboglobulin; β-TG) and complement activation (C3 activation products; C3a) were also measured. PUU showed significantly higher levels of platelet adhesion than the other PUs. However, PU-PTMG (MW, 1500) showed the lowest platelet adhesion among the six PUs, comparable to that of HEMA/St. The β-TG levels of each polymer also corresponded to the platelet adhesion results. Furthermore, complement activation was inversely correlated with the results for platelet adhesion and activation potentials, except for HEMA/St, which showed the lowest platelet and complement activation levels. From their chemical compositions, we divided these PUs into three categories; (A) PUU, (B) PUs with a PTMG of lower MW and (C) PUs with a PTMG of higher MW. From our experimental results, we confirmed that, of these PUs, (C) showed the lowest levels of platelet adhesion and a higher activation level than (B), with (A) showing the highest platelet adhesion and complement activation level of the three categories. From these findings, it can be seen that the blood compatibility of the PUs was greatly influenced by the MW of the PTMG as the soft segment. We also found that the blood compatibility of the PUs varied according to whether urea binding was present.

Studies on surface structures of poly(ethylene oxide)-segmented nylon films

The surface structures of three kinds of poly(ethylene oxide)-segmented nylon (PEO-Nyl molten films were investigated using a scanning electron microscopy (SEM), an electron spectroscopy for a chemical analysis (ESCA), and a static secondary ion mass spectrometry (SSIMS). The PEO-Nys used were high semicrystalline PEO-segmented poly(iminosebacoyliminohexamethylene) (PEO-Ny610), low semicrystalline PEO-segmented poly(iminosebacoylimino-m-xylene) (PEO-NyM10), and amorphous PEO-segmented poly(iminoisophthaloyliminomethylene-1,3-cyclohexylenemethylene) (PEO-NyBI). SEM observations show that the surfaces of the PEO-Ny610 and PEO-NyMlO films are composed of spherulite, and that PEO-NyBI film has a smooth surface. The results of ESCA and SSIMS exhibit the significant enrichments of PEO segment at the surfaces of all the films regardless of the crystallinity. The reason for the enrichment of PEO segment was discussed in terms of the surface tension of the corresponding homopolymers in the melting state.

Polyether-segmented nylon hemodialysis membrane. VII. Studies on surface structures of various poly(ethylene oxide)-segmented nylon membranes

The relationships of the surface morphologies to the surface chemical compositions in poly(ethylene oxide)-segmented nylon (PEO–Ny) membranes prepared by the phase-inversion method were studied using scanning electron microscopy (SEM), electron spectroscopy for chemical analysis (ESCA), and static secondary ion mass spectrometry (SSIMS). The PEO–Nys used were high semicrystalline PEO-segmented polyiminosebacoyliminohexamethylene (PEO–Ny610), low semicrystalline PEO-segmented poly(iminosebacoylimino-m-xylylene) (PEO–NyM10), and amorphous PEO- segmented poly(iminoisophthaloyliminomethylene-1,3-cyclohexylenemethylene) (PEO–NyBI). SEM observation showed that the surfaces of the PEO–Ny610 and PEO–NyM10 membranes were composed of crystalline spherulite and that the PEO–NyBI membrane surface had a nodular structure. ESCA analysis exhibited the enrichment of the PEO segment at the surfaces of the PEO–Ny610 and PEO–NyM10 membranes. On the other hand, the enrichment of the Ny segment was observed in the case of the PEO–NyBI membrane. SSIMS analysis revealed that the outermost surfaces of the PEO–Ny membranes except the PEO–NyBI membrane were almost covered with the PEO segment.

Improved Nonthrombogenicity of Heparin Immobilized and Sulfonated Polyurethane: In Vitro Evaluation Using Epifluorescent Video Microscopy

We have developed novel surface modification techniques to improve the blood compatibility of Polyurethane (PU). One was heparin immobilization using a polyethylene imine spacer and the other was a sulfonated polyallylamine grafting onto a PU surface. Both techniques utilized ozone-induced graft copolymerization, thereby having an advantage to be applied to medical devices even with a complex design. In vitro lood compatibility of modified PUs were eveluated using an epifluorescent video microscopy (EVM) combined with a parallel plate flow cell. Both modified PUs showed significantly less platelet coverage on the surfaces with less β-TG and C3a production compared to the control. These results suggest that both PU-PEI-HEP and PU-PAA-S03 surfaces are promising for the application to a variety of medical devices.

Surface Characterization of Hema-Styrene Block Copolymer Using Transmission Electron Microscopy

We have already demonstrated that an amphiphilic block copolymer composed of 2-hydroxyethyl methacrylate(HEMA) and styrene, HS, showed excellent blood compatibility. The present study was carried out to characterize the surface structure of HS under dry and wet conditions, and after 372 days implantation as a vascular graft, using transmission electron microscopy (TEM). The HS which contains 63 wt% of polyHEMA segment was synthesized by the coupling reaction between semitelechelic polyHEMA and telechelic polystyrene. Under dry condition, the top surface of HS film was almost completely covered with polystyrene segment. On the other hand, at the surface after hydration, the polystyrene microdomains wrapped with PHEMA segments stretched toward the water side, which indicated surface restructuring in response to environmental changes. Protein layer thickness on the graft surface after implantation measured by TEM indicated to be less than 200 A, and in the microdomain structure beneath the protein layer with an alternate arrangement of polystyrene and PHEMA segments, stretched domains could not be recognized. These differences in the surface structures might be attributable to differences of the ambient environment. Moreover, such surface dynamics might influence the blood compatibility of HS.