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Biomedical subjects

K Senshu

Publications and source records attributed to K Senshu.

5 recordsLinked to original sources

Nonthrombogenic polymer vascular prosthesis.

Although many synthetic vascular grafts have been developed and evaluated experimentally or clinically, none of them have met long-term patency when applied as a small diameter vascular substitute. We have recently developed a small caliber vascular graft (3 mm i.d.) using a nonthrombogenic polymer coating. The graft consists of three layered structures: Dacron for the outer layer, polyurethane in the middle layer, and a HEMA/styrene block copolymer (HEMA-st) coating for the inner layer. HEMA-st is an amphiphilic block copolymer composed of 2-hydroxyethyl methacrylate and styrene which has demonstrated improved blood compatibility over existing biomedical polymers in both in vitro and ex vivo experiments. Ten grafts were evaluated in a dog bilateral carotid replacement model. The grafts were electively retrieved at 7, 14, 30, 92, and 372 days after implantation. All grafts were patent without detectable thrombi along the graft length including anastomotic sites. Scanning electron micrographs of retrieved graft lumen showed fairly clean surfaces covered with a homogenous protein-like layer without microthrombi or endothelial cell lining. The thickness of the surface protein layer measured by a transmission electron microscopy was what can be described as monolayer protein adsorption regardless of implantation periods of as much as 372 days. A stable monolayer adsorbed protein layer formed on HEMA-st surfaces demonstrated nonthrombogenic activities in vivo and secure long-term patency of small caliber vascular grafts with the absence of an endothelial cell lining.

Animals↗

In vitro evaluation of platelet/biomaterial interactions in an epifluorescent video microscopy combined with a parallel plate flow cell.

Suitable evaluation systems are critical for ranking various biomaterials in order to develop a method to design and synthesize nonthrombogenic biomaterials. We have recently developed an in vitro test system to evaluate platelet/biomaterial interactions in whole blood. The system consists of a parallel plate flow cell and epifluorescent video microscopy (EVM). A glass coverslip coated with a polymer was incorporated into the flow cell, and blood was perfused using a syringe pump via a polymer-coated PVC tubing connected to the flow cell. Whole human blood was anticoagulated with heparin (2 U/ml), and the platelets were labeled with the fluorescent dye mepacrine (5 microM). This system permitted real-time and dynamic observations of platelet/biomaterial interactions in whole blood under a defined flow condition. In order to evaluate the feasibility of this system, two different segmented polyether-polyurethanes (SPEUs), PU-PTMG(650) and PU-PTMG(2000), were chosen as test polymers. Surface characteristics verified with electron spectroscopy for chemical analysis (ESCA) and contact angle measurements showed similar results in both SPEUs. Blood was perfused at a wall shear rate of 200 s-1 for 20 min. Excitation light was applied for 2 s at 1 min intervals. The real-time image was then analyzed at each time point for the percentage of surface area of platelet coverage. Plasma beta-thromboglobulin (beta-TG) levels were also measured before and after each run. PU-PTMG(650) showed a significantly higher number of adhered platelets than PU-PTMG(2000) at each time point.(ABSTRACT TRUNCATED AT 250 WORDS)

Biocompatible Materials↗

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.

Allylamine↗

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↗

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-butanediol(BD)) and the same hardness of 80A. The EVM measured the amount of platelet coverage on the surfaces using human whole blood perfused 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.

Biocompatible Materials↗