The effect of hemodialysis (HD) using the cuproammonium processing membrane (CAPM) on the host immune system was studied in maintenance HD patients. Plasma C3a and C5a concentrations at the inlet and outlet of the dialyzer were measured during HD. Anaphylatoxins such as C3a and C5a were generated in the blood through the CAPM dialyzer, and the amount of anaphylatoxins generated correlated with membrane area. The effect of the Limulus test-positive substance, which was assumed to be β-glucan, on interleukin-1 (IL-1) and β2-microglobulin (β2-M) production activity of peripheral blood monocytes from HD patients on the CAPM and polymethylmetacrylate membrane (PMMA) dialyzers was also studied. IL-1 was bioassayed using C3H/HeJ mouse thymocytes. β2-M was radioimmunoassayed. IL-1 production activity of the monocytes from patients on CAPM was significantly higher than that of patients on PMMA and healthy volunteers. Moreover, β-glucan stimulated IL-1 production activity of the monocytes. However, inactivated serum from long-term HD patients inhibited IL-1 production activity induced by LPS and β-glucan. The washing solution obtained from the CAPM dialyzer and β-glucan stimulated β2-M production activity of the monocytes in vitro and in vivo. β2-M production activity of the monocytes from HD patients was significantly lower compared to that of healthy volunteers, but it was significantly higher for patients on CAPM than for those on PMMA. The intravenous injection of the washing solution from the CAPM dialyzer also increased β2-M concentration in the monocytes for all groups, but it was significantly higher for healthy volunteers than for patients on CAPM and PMMA. These findings suggest that bio-incompatibility of the dialyzer membranes and eluted material lead to not only intradialytic symptoms but also chronic inflammatory syndrome.

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Our research of lymcyte (Lym) adhesion property to fiber materials summarized that the fiber diameter highly affects Lym adhesion, especially, the ultra fine fiber less than 3μm shows remarkable adhesion of Lym, and that the configuration of non-woven web reduces flow resistance and enables rapid treatment process of blood filtration compared with the mass of fiber. Adapting these technologies for lymphocytapheresis (LCP), we have developed the extracorporeal leukocyte removal filter “CELLSORBA” and the filtration lymphocytapheresis method using this filter. The clinical evaluations verified that this filter can remove Lym at twice higher efficiency than the centrifugal method and that the LCP can be carried out in the safe and simple conditions.

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Thoracic duct drainage has been clinically used for immunomodulation in autoimmune diseases and pretreatment of kidney transplantation. However although clinical usefulness has been advocated, actual application has been limited probably mainly due to complexity in its maneuver. In an attempt to solve the problems, a novel CTDD system which utilizes filtration of lymphatic fluid to collect lymphocytes has been devised and evaluated both experimentally and clinically. Animal experiments in mongrel dogs using membrane filters with pore size 0.8 micron revealed good results showing a lymph flow rate of 40-90ml/h and a number of lymphocytes of 2.0-4.3×10⁶/ml thoroughly trapped in the filter. In clinical applications, a small membrane plasma separator was used. Up to 10⁹/day of lymphocytes were trapped in up to 2000ml/day of lymph collected in three malignant rheumatic arthritis patients. Clinical symptoms have been miraculously ameliorated with a marked reduction in a Leu 3a/Leu 2a ratio and improvement in ESR. In conclusion, as proved to be simple in manipulation and reliable in function, the system is expected to open a new era in extracorporeal immunomodulation therapy.

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Immunoadsorption is interpreted as an adsorption utilizing the immunological reaction, in a narrow sense. When using the word in broad sense, the specific or selective adsorption of pathogenic immune reactants by the affinity adsorbent is included in immunoadsorption. There are several immunoadsorbents currently available for clinical application and some are undergoing clinical test, which have given us fairly good results. These procedures, replacing plasma exchange, have a promising future in the treatment and also elucidation of the pathphysiology of immune diseases.

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5 Patients with active rheumatoid arthritis (RA) were treated with the plasma exchange therapy. In coculture of patient T cells plus patient B cells, IgM-RF production was reduced without significant changes of total IgM production after the therapy. This phenomenon was not associated with changes in percentages of T cell subsets. These results may imply recovery of the suppressor signal from T cells and/or responsiveness of B cells to that signal. On the other hand, 23 patients with RA were treated with a low dose (2 to 5mg/kg/day) of cyclosporine A. Two-color flowcytometric analysis showed significant reductions of percentages of T cells having HLA-DR antigen at the end of study.

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It is well recognized that plasmapheresis (PE) or double filtration plasmapheresis (DFPP) may play a role on improving the depressed tumor-survillance system and enhancing the effects of chemoimmunotherapy by removal of various immunosuppressive factors in cancerpatient plasma. Our present study indicates that PHA inhibitory factor and NK inhibitory factor are effectively removed only by DFPP and that IAP, α-AT and IL2 inhibitor which can not be removed by DFPP system can be removed by multiporous glass beads adsorbents (100Å). 14 out of 28 patients treated with DFPP showed the improvement of subjective symptomeso These results suggest that DFPP plus aggressive chemoimmunotherapy should be needed for more useful adjunct therapy of far-advanced cancer patients.

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The present study was performed to 23 patients with lupus nephritis (LN), who were able to be followed up about clinical manifestation and laboratory examination for more than 1 month before PEx and 1.5 years after PEx. They were investigated about effect of PEx on lymphocytes subsets, circulating immune complex (IC), IgG, CH₅₀ anti-dsDNA, ANA and renal histology. After PEx undergone, Leu4, Leu2a significantly increased, IC, IgG, anti-dsDNA and ANA significantly decreased, and CH₅₀ recovered into normal range. Light microscopy showed improvement of renal pathological findings, although electron microscopy did not reveal significant reduction of immunedeposits in lupus lesions. We conclude that PEx is beneficial maneuver against immunological abnormality in patients with severe LN.

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Recently it is becoming more and more realistic to have a totally implantable cardiac prosthesis. Since this system involves a power system, an implantable feedback sensor and a mechanical driving system, it is easy to predict the needed technologies for this and other implantable artificial organs. 1. Power delivery: (i) Continuous delivery of up to 50 watts is possible in a transcutaneous fashion for over 5 years. (ii) Implantable batteries that may be recharged up to 1000 times are feasible. (iii) Management of heat packages up to 1, 000°C are possible. (iv) Implantable packages of the above mentioned systems are already available. 2. Implantable sensor: (i) Implantable intrinsic sensors such as position sensor are developed and have proven to be feasible. (ii) Reliable implantable extrinsic sensors such as glucose or oxygen sensors are not available to guarantee a continuous reliable operation of implantable systems. 3. Diagnostic system for a totally implantable system: (i) Transcutaneous transmission of diagnostic signal is feasible. (ii) Either direct or telemetrized diagnostic signal processing is feasible. 4. Implantable artificial organ system: (i) Mechanical or hydraulic system have already been proven feasible. (ii) Feasibility of chemical systems are currently difficult to establish. Thus, if only electro-mechanical or electro-hydraulic systems are involved, a totally implantable artificial organ which can function up to 2 years is possible. However, in order to develop any metabolic regulating artificial organs, there are many technical problems which still exist before for possible clinical implantation. Unconventional approaches are necessary for this type of metabolic implantable artificial organs.

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The final goal the development of artificial organs is to implant completely inside the body. One of the obstacles to realize this purpose is how to develop an enrgy source. Especially, it is more serious for an artificial organ such as artificial heart in which a large energy is required. There are two methods to supply energy to an artificial organs implanted inside the body. 1) To implant an energy source inside the body. 2) To transmit the energy to the inside from an energy source carried outside the body. In this paper, it will be mentioned about the present status of enrgy sources and enrgy transmission.

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It is gradually becoming possible to synthesize polymeric biomaterials which have considerable biocompatibility, owing to comprehensive studies by biomaterial scientists. Most of the biocompatible materials can be produced by surface modifications of the polymeric materials with mechanicals properties matching with those of the surrounding living tissues.
It is shown that the polymeric materials with bioinert water-soluble chains on their surface exhibit minimal protein adsorption and cell adhesion, while chemical fixation of collagen molecules onto polymeric surfaces leads to district adhesion of the materials to the surrounding tissue.
Biocompatibility, Polymeric biomaterials, Bioinert, Bioadherent, Surface modifications

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It is extremely important for developing a completely new product to predict its conditions of use and expected formance. Even if these are not clear a preliminary design Based be defined based on assumptions as to the operating conditions. Based on the preliminary design, a prototype of the product may be developed, and this can be evaluated by function and performance tests and also reliability tests under various alternative conditions to determine whether the product will meet the various conditions required. If the prototype does not meet the requirements or conditions, it is necessary to improve it and to check or review the adaptability of the operating conditions and the specification of the original design. It is the required specification of a new product that finally determines whether the design is satisfactory or not. If the target is a more complex product, such as an implantable artificial heart, it is more difficult for an engineer to make decisions by himself. In this case a contact point between medical science and engineering is necessary, and it is necessary to develop a specification which is the result of a consensus among the experts of the medical field.

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The inplantable artificial kidneys designed to treat uremic toxins in the intestinal tract have been developed. This system has been composed of two parts. The one is the hemofilter used with high permeable membranes, and the other is the intestinal tract. It is revealed experimentally that theselectivity of adsorption for many kinds of solutes in the lower alimentarytract is capable to act for renal tubules in animal. The most important thing is to develop the biocompatible hemofilters, in order to examine biocompatibility of biomaterials, C3a, β-TC, 112, elastase arerevealed that PMMA rembrane are most combatible material for developthe today.
It seems to indicate a step forward inthe development of implantable artificial kidney, if biocompatible new materials are developed.

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The trend in development of artificial endocrine pancreas is now from bedside-type to wearable and even to implantable one. However, there still remain many problems to be solved in each part of the device. Technologies derived from progress in the development of various implantable organs will be beneficial for realization. Problems awaiting solution in glucose sensor, processor and effector are summarized.

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Pump material, pump design, actuator, energy source, and control are major technical factors for the development of totally implantable artificial heart system. The most important problems among them are related to pump material, actuator, and energy source. Completely antithrombogenic, durable, and stable materials are not yet available. Lack of small-sized, high-powered electric motors makes us difficult to design an implantable small actuator with enough power for the blood circulation. Since totally implantable energy source is not in hand, transcutaneous electric energy transmission systems are being developed. With these systems, we have to carry fairly large chargeable batteries outside the body.

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Hydrogel is a water swollen “soft material” made of synthetic polymers. We found that the hydrogels can contract and dilate reversibly under electric stimulus (Electro-Activated Mechanochemical System). On the base of this principle a variety of biomedical divices such as artificial muscle lifting up and down the load repeatedly, permselective chemical valve membrane opening and closing the pores, controlled drug delivery systems (missile drug model) and others were developed.

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This paper summarizes today's state-of-the-art in precision manufacturing and ultra precision manufacturing which have a very important role for manufacturing the valued products Typical products being manufactured to ultra precision range and manufacturing processes are introduced in the paper. The attainable accuracy in precision machining with time has been estimated from the product data realized in the past. A national project on ultra precision manufacturing is also mentioned briefly, introducing the technological problems that have to be solved.

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As electronics represented by computers makes progress, comparable actuators of small size and high-speed response are in strong demand. This ultrasonic motor is based on an utterly new principle where the rotating force is obtained by an ultrasonic vibration. It is greatly noticed as the actuator of this age because it has a very large torque per unit volume and an excellent controllability as compared with existing motors which are operated by the interaction of an electric current and a magnetic field. Two types of ultrasonic motors and their driving circuits have been developed. One is the ring type which allows uniqe applications, and the other is the disk type, which is easy to support, having wide general uses. This paper describes the principle of operation, construction, driving circuit, etc. of these ultrasonic motors.

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A medical treatments for persons who recieved severe damages to an organ and failed to recover its functions has been an application of the artificial organ or the organ transplation. Recently, a new type of artificial organs, called a cell incorporated artificial organ (or a biologically reconstituted organ, or a cultured artificial organ) has been developed to save patients who cannot receive such conventional medical treatments. The new technique of artificial organs features such as (1) applicability for the multifunctional organs like a liver and (2) avoidance of the immunological rejection by using the patient's cells. In this paper the author summarizes the development of cultured artificial skins which have been most investigated among the cultured artificial organs and have been clinically applied. The possibility of a cultured liver is also discussed briefly. Before a settlement of the cultured organn as a clinical technique of the artificial organ, the following methods must be established: (1) rapid proliferation of parenchymal cells of an organ. (2) long-term in vitro maintenance of parenchymal cells. (3) three-dimensional mass cultures of cells.

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Shape Memory Alloys which are one of the new functional materials are developing on the metallurgical research and application. These alloys have two specific properties of Shape Memory Effect and Super Elasticity. Ti-Ni, Cu and Fe Systems are practical materials. Researches are developing on 1) The new Shape Memory Alloys, 2) Discover of new Shape Memory Effect, 3) Workability, 4) Materials production by powder metallurgy. The problems to be clarify in future are 1) Prevention of deterioration and increase of life time, 2) The biocompatibility. There are many applications on industry machine, energy, medicine, architecture, electronics, subsistence goods and so on. In the medical field, applications are developing on artificial heart, dentistry and others.

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Poly (2-hydroxyethyl methacry late) (PHEMA)/polyamine graft copolymers (HA) were prepared, and their interaction with rat platelets was examined by the use of column method. Significantly, platelet adhesion was minimized on the surface of HA copolymer with particular contents of polyamine (2-7 wt%) under the physiological conditions. Through the study using cytoskeleton-disrupted platelets, it was concluded that adhesion of platelets on HA surface was caused primarily by ionic interaction between platelets and microphase separated surface of HA. Thus, change in protonation degree of polyamine grafts with surrounding pH crucially affect the platelet retention. Actually, retention of platelets on HA was increased with increasing the protonation degree of amino groups in polyamine grafts. From the above results, it was suggested that concentration and domain-structured distribution of the protonated amino groups on HA were the determining factors for platelets adhesion on HA copolymer surfaces.

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Ex vivo evaluation on the non-thrombogenic properties of polyether-segmented nylon 610 was made in terms of estimating changes in the number and adhesiveness of circulating platelets with the construction of arteriovenous shunt in rabbit. The copolymers with particular microstructure exhibited unique feature toward eliminating the activation of contacted and/or adsorbed platelets on their surfaces, which indicates the control of crystalline-amorphous microstructure as the promising concept for the molecular design of non-thrombogenic materials with semicrystalline states.

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In order to clarify the relationship of rat platelet cytological changes to block copolymers with surface free energy gaps between the microdanains, PHEMA, PSt, HEMA-St block copolymer, FAA-St block copolymer, and HA-St block copolymer were prepared and their interaction with platelets was investigated by TEM. From this TEM analysis, the release of storage granules in the adhering platelets was found to be remarkably suppressed at the HEMA-St and FAA-St surfaces compared with hanopolymers and HA-St surfaces.

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An evaluation using FPU as an intra-aortic balloon was made. It was inserted into the descending aorta of dogs, and drived without heparin. From the aortography, good motion of FPU balloon was observed. After driving for 24 hours in max, there were no gross macroscopic thrombi, and from the observation with SEM, negligible blood components were found on the surface of the balloon. We did not find any problem about the strength of FPU balloon, nor remarkable changes of coagulation factors during experiments. In compared with the widely used Cardiothane balloons, there were no significant differences about the blood compatibility. Thus, PFU will have possible application as a new biomaterial of intra-aortic balloon catheter for clinical use.

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The adhesive plasme proteins such as fibrinogen, fibronectin, vitronectin and von Wil lebrand factor have the common cell attachment site; Arg-gly-Asp (RGD), which was recently identified. We investigated the role of platelet receptor-protein's ligand mechanism by using synthetic RGD-Ser (IDS) on the interaction between platelet and artificial surface. RGDS inhibited platelet adhesion, aggregation and shape change of adhered platelets on fibronectin-coated substrate in a dosedependent manner, but showed partial inhibition for fibrinogen even in high concentration. we can conclude that RGD receptor-ligand interaction between platelet and plasma proteins is the dominant factor for platelet adhesion, activation and aggregation on the artificial surface, although there may operate partly other interaction mechanism for adsorbed fibrinogen.

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Heparinized chitosan membranes were prepared from a polyion complex between quarternized chitosan and sodium heparin. Ultrafiltration rates for these membranes were decreased with an increase of the degree of heparinlzation. Also, these membranes could perfectly permeate solutes of low molecular weight such as urea, creatinine, glucose and vitamin B₁₂ and completely reject protein such as alubmin. No thrombus was macroscopically observed on the heparinized chitosan membranes in vivo.

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The araphylatoxins (C3a & C5a) generated upon extracorporeal circulation often cause adverse reactions at local and systemic levels. In this paper, the principle, surface molecular design and highly selective adsorptional behaviors of anaphyatoxin-scavenging materials were demonstrated. Both C3a and C5a are highly basic proteins, so that the negatiuely-charged surfaces could selectively adsorb these basic proteins from abundant proteins which are mostly negatively-charged in blood. The introduction of negatively-charged groups on the surface greatly absorbed C3a and C5a. This gave us the logical basis of the device under development.

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The new immuno-adsorbent containing high affinity to immunogloblin was applied to the T, B-lymphocyte separation. L-aspartyl-L-phenylalanine methyl ester and sulfathiazole turned out to be highly selective ligand to B-cell. In order to supPress the nonspecific adhesion of T-cell, carrier (matrix) polymer beads, and coupling reagents as spacer were selected.

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A new material “magnetic liquid”, packed in the torus silicone bag, was implanted in the circumferential tissues of the Colostomy in ten beagle dogs. A special magnetic cap which became magnetized radially, was inserted into the stoma. The stoma was tightened circumferentially by magnetic force between the cap and magnetic liquid. The leakage of ferces besides the magnetic cap was not observed in the Cases in which the magnets were strong enough more thane 4000 Gausses.

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When irradiated with 433-MHz microwave (MW) to the polymeric prodrug of methotrexates coupled with biodegradable poly (hydroxypropyl)-L-glutamine (PHPG), its temperature rise was higher than that of neutral PHPG. Polyelectrolytes which showed large values of the relative loss factor (ε") were easy to generate heat by 433-MHz MW irradiation. When a strong Polyelectrolyte (PE) was injected into the phantom simulated to muscle tissue in value of ε", it was confirmed that the PE was more heated than the phantom by external MW irradiation. A localized drug-admlnistration induced by selective microwave irradiation, that is, a physical targeting can be expected if the macromolecular prodrug in polyelectrolyte system is utilized.

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We have developed a new IL-2 slow release system (IL-2 mini-pellet) using collagen from bovine Skin. Serum IL-2 activity after a single s. c. abministration of IL-2 mini-pellet, in which 1×10⁶u of IL-2 was included, could be sustained until 72 hours. The activity of NK cells and cytotoxicity of LAK cells in the mouse spleen were effectively augmented after an administration of IL-2 mini-pellet. In histological study using monoclonal antibodies, a large number of Lyt-2 positive cells and L3T4 psitive cells were induced around the IL-2 mini-pellet. The adoptive immunotherapy by LAK cells and IL-2 mini-pellet showed a remarkable inhibition of lung metastasis and was more effectively than the adoptive immunotherapy by LAK cells and IL-2 in PBS. It is suggested that IL-2 mini-pellet is effective IL-2 slow release System in adoptive immunotherapy using LAK cells.

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Adriamycin (ADM) was immobilized on biodegradable gelatin (G) together with coagulation factor XIII (XIII) and human thrombin (T) to provide a new anticancer material, G. T. XIII-ADM. In vivo study confirmed that the material enhanced the local accumulation of fibrin and the topical stay of ADM in the pleural cavity. Clinically, G. T. XIII-ADM and fibrinogen were applied to cases with severe pluritis carcinomatosa. The rapeutic effects were excellent both clinically and pathologically. These effects were attributed to both adhesive and oncolytic effects of G. T. XIII-ADM and fibrinogen. We defined this therapy as Bio-Adhesio-Chemo (BAC) Therapy.

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We reported that an autogenous connective tissue tube with temporary antithrombogenic property showed an excellent healing process when it was applied as vascular substitute. Howover, in the method to give anti-thrombogenicity some complicated techniques were required and it took 1 hour for the entire process. To overcome these problems, a simpler and swifter method was developed in this study. Both ends of connective tissue tube which had been implanted into the subcutanous tissue for 3 weeks wer exposed, and the tube was treated ed in situ with 3% protamine, 1% glutaraldehyde and then 1% heparin. It took only 15 minutes for the process. Thereafter, the tubes, about 6cm in length, were segmelltally repalced with bilateral carotid arteries of the same dog. The viability of connctive tissue after the treatment using glutarldehyde was well preserved histologically, and heparin content of the tube examined by 3H-labelled heparin and X-ray microanalysis was sufficiet. The inner surface of the connective tissue tube which had been replaced with the carotid artery for 25 days was smooth without any thrombus, and histologically was covered with grown endothel, rich in newly developed capillaries. These results indicate that this method is applicable to in situ heparinization of artery after thromboendarterectomy as connective tissue graft for a vascular subsitute.

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To overcome the disadvantage of cross-linking of glutaraldehyde (GA), polyepoxy compounds were newly introduced. However, the effects of crosslinking of polyepoxy compounds on antigenicity has not been clear. In this study, the changes of the antigenicity of vascular xenograft treated with GA or glycerol polyglycidyl ether (GPE), one of polyepoxy compounds, were examined. Fresh artery of a donor dog was cut into three pieces. As test antigen, two of them were treated with GA (GA-group, n=7) or GPE (GPE, n=7) and the Temaing was untreated (N, n=7). As a positive control, the donor lymphocytes were used (Ly, n=4). DDY mice were inoculated with these antigens twice and then their sera were collected. As a negative control, normal mouse sera were used (MS, n=5). Using these sera, donor lymphocytes which had the antigens shared on artery and lymphocytes were stained with FITC labeled anti-mouse IgG antibody and analysed by flow cytometry. The maximum ratio of the stained lymphocytes was counted and calculated in percentage. In MS-group, the percentage was 0.4±0.3% (mean±S. D.), while in Ly-group, it showed 90.3±6.5%. In N-group, the percentage was 32.0±22.0% which was significantly higher than that in GA-group (1.7±1.1%, p<0.005) and GPE-group (2.1±3.1%, p<0.005). These results show that GPE has excellent properties to reduce the antigenicity of biological materials for medical use no less than GA.

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The effect of age on tissue response to biomaterials was studied by the subcutaneous implantation of 4 polymer films in rats between 6 weeks and 21 months of age. No marked difference in the cellular response was observed among different ages. although the youngest rats initially showed a slightly more intenseresponse and the oldest showed less response. The remarkable effect of old age was observed in the thickness of fibrous tissue surrounding the implants. The oldest rats only formed significantly thin capsule, suggesting the different type of tissue response.

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A substitute for the cardiac wall was newly developed. This was composed of colagen coated ultra-fine polyestermesh (CUFP), which has suitable thickness and pliability, ease in suturing, good affinity to the native cardiac wall, antithlombogenicity, good healing quality, and no future degeneration such as hypeltrophy, shrinkage, calcification, or aneurysmal diatation; these are the ideal requhements for the substitute. The animal experiment as a patch in the right ventricular outflow tract of 33 dogs revealed the superior properties described above compared with a control, the glutaraldehyde treated equine pericardium. Light microscopical observations showed rapid and stable healing of the graft wall.

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The physical properties and biocompatibility of apatite-collagen composite were tested Carbonate-hydroxyapatite, CO₃-Ap, which showed chemical composition and crystallinity similar to bone was synthesized (pH 7.4±0.2, 60±1°C). CO₃-Ap was mixed with type I atero-collagen solution whose antigenicity was removed by enzymatic treatment and formed into apatite-collagen implants. These apatite-collagen composites exposed to UV irradiation for 4 hours reduced their solubility remarkably. These UV treated apatite-collagen composites implanted into submusclofacial part of rat abdomen showed good biocompatibility when examined histlogically.

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Pericardial adhesions increased the morbidity of reoperative cardiac surgical procedures. Attempts to reduce these adhesions have had limited success. Antiadhesive pericardium with heparin slow release was newly developed. The membrane was cross-linked by glutaraldehyde and heparinized ionically using protamine. Animal studies revealed that the membrane had excellent antiadhesive property. No or little adhesions were observed between the heart and the pericardial patches in 6 out of 7 dogs. It didn't cause a fibrotic reaction at the epicardial surface. Glutaraldehyde-fixed ethanol-preserved porcine pericardium with heparin slow release is a safe, effective pericardial substitute and must serve to prevent most postoperative cardiac adhesions.

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In order to exzamine the biocompatibility and adhesion to soft tissues with artificial materials, we evaluated HA implanted transcutanously and transperitonealy in rats for 20 weeks. Compared with Dacron materials, adhesions of HA were poor in early phase of experiments, especially in small pore sized HA. However, in the longer time, adhesion and biocompatibility of HA implants became completely, as no inflamatory reactions, and skin down growth phenomenons were observed. These results are proved HA to be superior materials in both biocompatibility and adhesion to soft tissues. HA are expected to be applied as peritpneal catheter cuff to prevent from peritonitis and tunnel infections of CAPD.

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This study was made to clarify the interactions of synthetic materials with human blood coagulation and complement system. Three kinds of test tubes of polyvinylchloride (PVC), hydrogel with long polyethyleneoxide chains (PEO-H) and heparinized hydrophilic polymer (H-PSD, Anthron) were evaluated. Fresh whole blood was put into the tubes and incubated at 37°C. Whole blood clotting times were 15 mins for PVC and 45 mins for PEO-H, but blood did not coagulate in the H-PSD tube. Contact activation of blood coagulation was significantly suppressed in the PEO-H tube because of volume restriction effects derived from the long FED chains. Antithrombogenicity of H-PSD was due to the complex made from heparin on the H-PSD surface and antithrombin III in the blood. C3a and C4a were elevated remarkably in the PVC tube, but in PEO-H, especially in the H-PSD tube, their elevations were suppressed. The C5a elevation was not seen in any tubes. It is concluded that complement activation was suppressed on the surfaces of antithrombogenic biomaterials.

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Antiadhesive pericardium with heparin slow release was newly develcped. Fresh porcine pericardium was soaked in distilled water and sonicated in order to cause cell destruction. In this way, a natural tissue membrane composed of collagen was obtained. The membrane was crosslinked by a hydrophilic epoxy compound instead of glutaraldehyde to maintain the natural tissue elasticity and hydrophilicity, and heparinized ionically using protamine as a binding site. Heparin prevents the precipitation of fibrin, which leads to cellulofibrous adhesive tissue. Therefore, the membrane with heparin slow release can prevent the adhesion in its early stage. Animal experiment revealed that the membrane had excellent antiadhesive property. The pericardium in the long term experiment was covered with a layex of mesothelial cells which has a natural and permanent antiadhesive property.

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We have developed a new method of polymyxin B immobilized to polustyrene fiber (PMX-F) for selective removing of endotoxin (Et). We previously reported the efficacy of PMX-F for endotoxin shock canine received Et. This study was aimed to detect the effectiveness of PMX-F wing direct hemoperfusion on endotoxic animals, and compare the effectiveness between the activated charcoal (DHP-1), and pre-immobilization fiber of polymyxin B (carrier fiber). Charcoal groups survived in the rate 20% (1/5), carrier groups survived in 0% (0/13) whereas PMX-F groups survived in 73% (11/15) with statistical significancy. It was observed that the treated group with PMX-F showed the quick recovery from severe hypotention.

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