For long-term clinical application of the wearable artificial endocrine pancreas, closed-loop subcutaneous insulin infusion algorithm has been developed by analyzing the kinetics of subcutaneous absorption of Insulin Lispro which was absorbed 2 to 3 times faster after subcutaneous injection than usual regular insulin. The wearable artificial endocrine pancreas with this algorithm was applied to control daily glycemic excursion in diabetic patients. Near-physiological glycemic controls for up to 7 days were obtained with this system. These data indicated feasibility of long-term glycemic control in diabetic patients with closed-loop subcutaneous insulin infusion by the wearable artificial endocrine pancreas.

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As alternative and a sophisticated way of glucose monitoring system, the development of non-invasive glucose monitoring system has been expected. We have examined the possibility of non-invasive glucose measurement by using Fourier transform infra-red spectroscopy with attenuated total reflection (ATR) prism. 1. Glucose has characteristic absorbance at the wave numbers of 1033 and 1080 cm-1, and the absorption intensities are proportional to glucose concentrations. 2. Glucose concentrations in the serum and whole blood samples could be measured quantitatively, if the base-line drifts and interferences other than glucose were subtracted, by expressing as the difference absorbance with the spectrum of fasting sample, as an individual characteristic. 3. With an application of calibration algorithm or the Chalcogenide optical fiber system to adjust the spectral changes due to the attachment pressure of ATR prism to mucous membrane, submucosal tissue glucose concentrations could be measured or monitored continuously by analyzing absorbance spectra through mucous membrane of lip. Although the improvement and further developments of the system in both hard-ware and soft-ware basis in order to improve measuring sensitivity should be necessary, the non-invasive glucose monitoring system will be available in the near future.

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We tried to control mass transport and microstructure in collagen gel applied to cell culture medium. An aqueous solution of type I atelocollagen of pigskin was cast into a glass Petn-dish and dried to control collagen concentration. Then, the semi-dried film of collagen was crosslnked with glutaraldehyde aqueous solution saturated by sodium chloride. Finally, a collagen-gel flat membrane was obtained after washing the crosslinked thin film with excess pure water. Analysis of intramembrane diffusivity of the membranes using the tortuous pore diffusion model represented that glutaraldehyde concentration at crosslinkng had no effect on microstructure of the membranes. On the other hand, intramembrane diffusivity of the membranes was depend on collagen concentration at crosslinking in the range of 77-96 wt%. The collagen concentration was also correlated with structural parameters of the membranes. In conclusion, we could obtain various collagen-gel flat membranes with different solute permeabilities and microstructures.

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We have reported that a fluorinated polyimide(PI) suppresses adsorption of plasma proteins. In this study, we will focus on finding adsorption mechanism of plasma protein onto PI surface. The amount of adsorbed protein onto polymer surface have been determined. To investigate surface properties of PI, zeta potential of PI and poly(styrene) (PSt) were measured by electrophoretic light scattering method. In the physiological conditions, the amounts of bovine serum albumin(BSA) and fibrinogen(Fbg) adsorbed on PI were 1/2 less than values measured for PSt. Zeta potential of PI was much lower than the value for PSt. These findings suggest that the suppression of protein adsorption of PI was attributed to the strong negative charge of the surface. The pH dependence of protein adsorption on PI membrane suggested that this electrostatic effect was stronger than the intra- and inter-molecular interaction change of plasma proteins. It is therefore concluded that the electrostatic force of repulsion between PI and BSA or Fbg should be effective to suppress the adsorption of these proteins.

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Between August 1994 and August 1997, GRF glue was applied to 55 patients, among whom 37 patieets with acute aortic dissection, four patients with chronic type A aortic dissection, six patients with true thoracic aneurysm and eight patients with heart valvular disease. There were six early deaths and one late death, however, causes of death did not relate to GRF. Especially in patients with acute type A aortic dissection, GRF proved to be very useful as adhesive. The adhered sites of aortic stump were tightly reinforced and had appropriate elasticity to suture. In other patients, GRF was used as a hemostatic agent and it was applied to the incised tissue. It also proved to be useful as hemostatic agent, however, it should be used after drying the application sites as much as possible. There were no side effects after surgery. We concluded that GRF glue was useful and efficient for adhesive and hemostasis.

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Complete closure of pericardium after coronaryartery bypass grafting has the advantage of avoiding injury of theheart and grafts during reoperation. The safety of Gore-tex surgical membrane was studied in this report. Between January 1992 to June 1997, 434 cases of CABG were performed. The hearts and the grafts were covered with either Gore-tex surgical membrane (329 cases: Gore-tex group), or auto-logous pericardium and/or other autologous tissue(105 cases: non-Gore-tex group). The rate of bilateral dissecion of the ITAs was higher in Gore-tex group. Operation time and cardiopulmonary bypass time was also longer in Gore-tex group, as compared to non-Gore-texgroup. But there was no difference between Gore-tex group(2.1%) and non-Gore-tex group(2.9%) in the development of postoperative mediastinal infection. There was no difference between Gore-tex group and non-Gore-tex group in the kind of organism of infection. MRSA in the most common organ-ism cultured from sternal wound infecions(3 cases in Gore-tex group 1 case in non-Gore-tex group). Overall hospital mortality was none. There was no statistial significance either between Gore-tex group and non-Gore-tex group in the period from operation of debridment to dischage(52.0 days in Gore-tex group, 46.3 days in non-Gore-text group). In conclusion, the clinical use of Gore-tex surgical membrane for CABG dose not appear to be a risk factor of postoperative mediastini-tis.

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We manufactured four types of cotton-like collagen hemostat which were made from atelocollagen fibers cross-linked by heat dehydration for use as topical hemostatic agents. Their fibers were 1) 15-25μm in diameter, 0.5 cm in length, 2)15-25μm in diameter, 1.0 cm in length, 3) 15-25μ m in diameter, 3.0 cm in length, and 4) 20-40μm in diameter, 3.0 cm in length. The hemostatic efficacies of these four hemostats were compared with a commercially available collagen hemostat ( Integran®) and oxycellulose ( Oxycel®) in the canine spleen under normal or low blood pressure. It was found that;type 4) and Oxycel® showed complete hemostasis under both normal and low blood pressure, and that Type 3) showed complete hemostasis only under low blood pressure. Type 4) showed higher hemostatic efficiency than Integran®or Oxycel®. The hemostasis rates of our hemostats were higher than those of Oxycel® within 3 min. after attachment of the hemostats. Tissue reaction to these collagen hemostats was minimal at two weeks after implantation.

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The segmented polyether urethanes (PEUs) have been used in implantable medical devices because of excellent mechanical properties, acceptable blood compatibility, and good biostability. However, recent studies demonstrated that polyether soft segment of PEU was susceptible to oxidative degradation in vivo due to the scission of the polyether group. Recently, polycarbonate urethanes (PCUs) having no ether linkage in the soft segment have been developed, and showed improved stability against oxidative degradation over PEUs. The present study evaluated blood compatibility of these PCUs in comparison to PEUs using our epifluorescent video microscopy (EVM) combined with a parallel plate flow chamber. We selected five PCUs: PCU(1090), PCU(1140), PCU(1150), PCU(1560) and Corethane 80A, and two PEUs: Pellethene2363-80AE and Tecoflex EG80A, all of which have similar hard segment compositions(MDI or HMDI: BD). The EVM measured the amount of platelet coverage on the surfaces using human whole blood perfused at a wall shear rate of 100s^-1 for 20 min. PCUs surfaces showed lower platelet adhesion comparable to PEUs. The amount of platelet adhesion depended on molecular weight of soft segment. Based on these results, it is recommenced that PEUs should be replaced by ether free PCUs for the application to implantable blood contacting devices such as artificial hearts and pacemaker leads insulations.

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We have proposed a portable cardiopulmonary bypass system mounted in anesthetic machine and we have been working to create a newly designed vane pump for this system. This pump worked as a perfusion, drainage, and suction pump. Regarding hemolysis, the plasma free hemoglobin level was below 200 mg/dl at the 4 hours operation. For diminishing hemolysis, we added one way valves in its rotor and separated pump to the inflow and outflow chamber.

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A novel asymmetric hollow fiber of 6FDA polyimide has been fabricated for intravascular oxygenator (IVOX) device. A dry/wet phase in-version process has been applied to a spinning process to prepare an asymmetric polyimide hollow fiber. The outer surface of the hollow fiber consisted of an ultrathin skin layer. O₂ and CO₂ transfer rates of the polyimide hollow fiber were much larger than those determined in presently available polydimethylsiloxane (PDMS) hollow fiber and the transfer rates were similar to those measured in silicone-layer-coated polypropylene (Si-PP) hollow fiber. The hemocompatibility of the polyimide hollow fiber without heparinization has been evaluated in vitro and in vivo. The amount of platelets on the polyimide hollow-fiber surface measured in vitro was less than that on PDMS hollow fiber and Si-PP hollow fiber. The formation of thrombus estimated in vivo was not found. This means that the asymmetric polyimide hollow fiber shows excellent hemocompatibility.

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We performed cochlear implantation in 4 three-year-old children. Special attention was paid to skin incision and temporal bone drilling for device embedding. The skin flap viability and wound healing was good and we did not experience any wound infection nor flap necrosis after surgery. Patients exhibited significant improvement in detection of environmental sounds, and production of speech increased gradually. Although the language development of a perilingually deaf boy was excellent, that of the remaining congenitally deaf children was slower. Early decision and application of the cochlear implant is necessary for better development of the spoken language in profoundly deaf young children.

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In a small-caliber vascular graft, neoarterial regeneration is essential to improve patency. The histological process of regeneration iscomplexly controlled by many structural and biological factors such asgrowth factors. Our designed segmented polyuiethane graft (innerdiameter, 1.5 mm;wall thickness, 100μm; length, 20mm), in which micropores (pore size, 100μm) were produced by excimer laser ablation technique. These grafts were coated with a mixed solution of photoreactive gelatin (20 mg/ml) and heparin (1mg/ml) with or without growth factors [vascular endothelial growth factor (VEGF), basic fibroblast growth factor(bFGF)], and were irradiated by ultraviolet light. Five grouped-grafts were implanted in aortas of rats for 4 weeks;the VEGF group (VEGF: 5μg/ml), the bFGF group (bFGF: 1μg/ml), the VEGF5/bFGF group (VEGF: 5μg/ml, bR3F: 1μg/ml), the VEGF50/bFGF group; (VEGF: 50μg/ml, bRIF: 1μg/ml) and the control group. Control grafts were treated without growth factors. The endothelial coverages were much greater for the growth factors-immobilized groups (around 50-60%) than that for the control group (around 30 %). At the midpoition of the three VEGF-immobilized groups, many capillaries were seen in the neoarterial intima as well as in the micropore, whereas such capillaries were scarcely observed in the bFGF group and control group. These results indicate that the impregnation of VEGF in the gelatinous layer of grafts enhanced transanastomotictissue ingrowth aswell astransmural capillaryingrowth.

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