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The repetition of forward and backward filtration during hemodialysis (HD) increases convective mass transfer, and thus, the authors devised a method of achieving cyclic repletion of ultrafiltration and backfiltration. Hemodialytic efficiencies of the developed unit are described. The devised method, named pulse push/pull hemodialysis (PPPHD), is based on the utilization of dual pulsation in a dialysate stream. Clearances of solutes with different molecular weights were determined, and in vivo hemodialytic performance was investigated in a canine renal failure model. Urea and creatinine reduction and albumin (ALB) loss were monitored, and the results obtained were compared with those of a conventional high-flux hemodialysis (CHD). Dialysis sessions were repeated eight times for PPPHD and six times for CHD by alternating PPPHD and CHD sessions in a single animal, which remained stable throughout the experiments. Urea and creatinine reductions for the PPPHD unit were 49.2 ± 2% and 44.3 ± 3.3%, respectively, which were slightly higher than those obtained for the CHD. Total protein and ALB levels were preserved by both methods. However, in vitro results revealed that PPPHD achieved significantly greater inulin clearance than CHD. The developed PPPHD unit facilitates repetitive filtration and improves convective mass transfer during HD, without the need for external replacement infusion.

Convective clearance during hemodialysis (HD) improves dialysis outcomes in kidney failure patients, and, thus, trials have been undertaken to increase convective mass transfer, which is directly related to internal filtration rates. The authors designed a new hemodialyzer to increase the internal filtration rates, and here describe the hemodia- lytic efficacy of the devised unit. The developed dual- chambered hemodialyzer (DCH) contains two separate chambers for dialysate flow within a single housing. By placing a flow restrictor on the dialysate stream between these two chambers, dialysate pressures are regulated independently. Dialysate is maintained at a higher pressure than blood pressure in one chamber, and at a lower pres- sure in the other chamber. The dialysis performance of the DCH was investigated using an acute canine renal failure model. Urea and creatinine reductions and albumin loss were monitored, and forward and backward filtration rates were measured. No procedurally related malfunction was encountered, and animals remained stable without any complications. Urea and creatinine reductions after 4-h dialysis treatments were 75.2 6.5% and 67.7 8.9%, respectively. Post-treatment total protein and albumin levels remained at pretreatment values. Total filtration volume was 4.98 0.5 L over 4 h, whereas the correspond- ing backfiltration (BF) volume was 4.77 0.6 L. The devel- oped dual-chamber dialyzer has the benefit of providing independent control of forward filtration and BF rates. HD using this dialyzer provides a straightforward means of increasing the internal filtration and convective dose.

Background/Aims: Because longer and/or more frequent dialysis has potential clinical benefits, home hemodialysis (HHD) systems should provide flexible renal replacement therapies. We propose a new cold dialysate regeneration system that requires 10 l per treatment for HHD. Methods: We designed a dialysate regeneration system using cold dialysate and 2 activated carbon columns alternatively switched between adsorption and desorption. Urea adsorption ratios were compared in three different conditions; cold dialysate (5.7°C), normal dialysate (36.8°C), and cold dialysate with washing. In vivo tests (n = 8) were conducted to validate this system. Results: The urea removal ratios were 20.0 ± 1.7% in cold dialysate, 36.0 ± 1.7% in normal dialysate, and 82.5 ± 1.2% in cold dialysate with washing. In animal experiments, the urea reduction ratio was 60.9 ± 6.3%, Kt/V was 1.0 ± 0.2, and serum electrolytes remained stable. Conclusion: The proposed cold dialysate regeneration system using a small volume of dialysate will be useful for HHD.

Background/Aims: Blood flow profiles in fiber bundles depend on the design of the arterial port and affects the biocompatibility of the hemodialyzer. We analyzed the effects of arterial port design on blood flow distribution in fiber bundles using nonintrusive imaging techniques. Methods: The velocity fields in arterial ports and the hemodynamics in fiber bundles were analyzed for hemodialyzers with different configurations using particle image velocimetry and perfusion computed tomography. Results: In a hemodialyzer with standard arterial ports, high blood flow profiles in the central and peripheral regions and low blood profiles in the middle region were developed due to jet flow and vortices around the jet. In a hemodialyzer with spiral arterial ports, higher flow profiles were developed due to the central vortices that decrease perfusion into the fiber bundles. Conclusion: The arterial port design of hemodialyzers should be optimized such that jet flow and vortices do not impair dialysis efficiency and biocompatibility.

Adequate intrathoracic anatomical compatibility is one of the most important considerations in designing a fully implantable total artificial heart (TAH). We have recently developed an innovative concept of reverse positioning of the aortic and pulmonary conduits to facilitate anatomical compatibility of the moving actuator type TAH. The pulmonary conduit of this TAH is designed to be located posterior to the aortic conduit, which results in a substantial reduction in the anteroposterior diameter of this heart, as well as the virtual elimination of the compression of the low pressure pulmonary conduit. In ovine orthotopic implantation experiments with this model of the TAH, we consecutively achieved 3 day survival in 1 sheep and 2 day survival in another. To the best of our knowledge, these were the first significant short-term survival cases in the orthotopic implantation of electric TAHs in sheep.

Research on pulsatile blood pumps for extracorporeal life support has been widely performed because of the proven advantageous effects of blood pulsation. However, studies on the use of pulsatile blood pumps for hemodialysis are limited, although available evidence demonstrates that pulsatile blood flow has a positive influence on dialysis outcome. Therefore, the authors designed a new pulsatile pump, which is characterized by minimal-occlusion of blood-containing tubing, no requirement for valves, and no blood flow regurgitation. Invitro hemolysis tests were conducted using fresh bovine blood, and the normalized index of hemolysis was adopted to compare blood traumas induced by the devised pulsatile pump and a conventional roller pump. In addition, experimental hemodialyses with a canine renal failure model were performed using the devised pump. Normalized index of hemolysis levels obtained was much smaller for the devised pulse pump (45 21 mg/100 L) than for the roller pump (103 10 mg/100 L), and no technical problems were encountered during dialysis sessions. Blood and dialysate flow rates were maintained at predetermined values and molecular removal was satisfactory. Postdialysis urea and creatinine reduction ratios were 61.8% 10.6% and 57.4% 9.0%, respectively. Pulsatile flow has usually been generated using pulsatile devices containing valves, but the valves cause concern in terms of the clinical applications of these devices. However, the described pulsatile pump does not require valves, and yet no blood flow regurgitation was observed. ASAIO Journal 2008; 54:191‐196.

A new dialysis modality was devised to increase convective mass transfer. Blood and dialysate are circulated by a pulsatile pump, but with pulsatile flow patterns that are 180° out of phase, which causes blood-to-dialysate pressure gradients to oscillate between positive and negative. In the present study, hemodialytic performance of the devised modality was investigated using a canine renal failure model. Membrane hydraulic permeabilities (Kuf) and fiber bundle volumes (FBV) were measured after each dialysis session. Postdialysis Kuf and FBV were then compared with those with conventional high-flux hemodialysis. No complications concerning animals or technical problems with the devised modality were encountered. Urea and creatinine reductions were satisfactory. Postdialysis Kuf and FBV values were significantly reduced after hemodialysis sessions, but were higher for the new modality. The devised modality incorporated with blood and dialysate pulsation offers a simple but safe means new mode of hemodialysis.

It is known that complex loading is involved in the development and maintenance of articular cartilage in the body. It means the compressive mechanical stimulation is a very important factor for formation of articular cartilage using a tissue-engineering technique. The objective of this study is to engineer cartilaginous constructs with mechano-active scaffolds and to evaluate the effect of dynamic compression for regeneration of cartilage. The mechano-active scaffolds were prepared from a very elastic poly(L-lactide-co-epsilon-caprolactone) (PLCL) with 85% porosity and 300-500 mum pore size using a gel-pressing method. The scaffold was seeded with 2 x 10(6) chondrocytes and the continuous compressive deformation of 5% strain was applied with 0.1 Hz for 10 days and 24 days, respectively. Then, the chondrocytes-seeded constructs were implanted subcutaneously into nude mice. Mechano-active scaffolds with complete rubber-like elasticity showed almost complete (over 97%) recovery at an applied strain of up to 500%. The amount of chondral extracellular matrix was increased significantly by mechanical stimulation on the highly elastic mechano-active scaffolds. Histological analysis showed the mechanically stimulated implants formed mature and well-developed cartilaginous tissue, as evidenced by the chondrocytes within lacunae and the abundant accumulation of sulfated GAGs. However, unhealthy lacunae shapes and hypertrophy forms were observed in the implants stimulated mechanically for 24 days, compared with those stimulated for 10 days. In conclusion, the proper periodical application of dynamic compression can encourage chondrocytes to maintain their phenotypes and enhance the production of GAGs, which would improve the quality of cartilaginous tissue formed both in vitro and in vivo.

Internal filtration contributes to convective clearance in high-flux hemodialysis but its contribution is limited by low pressure gradients. Therefore, a modification using a conventional dialyzer was conceived to enhance internal filtration and backfiltration (BF) rates. The modified dialyzer includes two longitudinal independent regions for blood flow, which were created by redesigning dialyzer caps. Blood pressures remained higher than dialysate pressures in one region and lower in the other region, allowing continuous internal filtration and BF in these respective regions. Modified and conventional dialyzers were compared in terms of pressure gradients and solute clearances. Thus, our experiments involved two groups: the modified dialyzer group and the conventional dialyzer group. A renal failure model was established using a dog weighing 25-30 kg by renal artery and vein ligation. With the exception of the dialyzers, experimental conditions were identical in the two groups. The pressure gradients between blood and dialysate were much higher for the modified dialyzer than for the conventional dialyzer. No significant differences were observed with respect to small solute clearances between the two groups, but mid-range solute clearances were significantly higher in the modified group. More optimization is required before the devised unit can be used clinically. However, the devised unit offers a straightforward means of regulating internal filtration and BF rates.

Mechano-active scaffolds were fabricated from very elastic poly(L-lactide-co-ε-carprolactone). The scaffolds with 80 % porosity and 300~500 μm pore size were prepared by a gel-pressing method. As a control group for elastic properties of polymer scaffolds, rigid poly L-lactide scaffolds were fabricated. The scaffolds were seeded with chondrocytes and cultured to evaluate the effect of elastic properties of polymer scaffolds for the differentiation and the ECM secretion of chondrocytes. Also, the chondrocytes-seeded constructs were implanted in nude mice subcutaneously to investigate their biocompatibility and cartilage formation. From the biochemical analyses, chondrogenic differentiation was sustained and enhanced significantly and chondral extracellular matrix was increased through mechanical stimulation of dynamic environment in the dynamic body systems. Histological analysis showed that implants of PLCL constructs formed mature and well-developed cartilaginous tissue, as evidenced by chondrocytes within lacunae. Consequently, the elastic PLCL scaffolds could be used to engineer cartilage in mechanically dynamic environments

Mechano-active scaffolds were fabricated from very elastic poly(lactide-co-carprolactone) by a gel-pressing method. The scaffolds were seeded with bone marrow stromal cells and the continuous compressive deformation was applied to cell-polymer constructs in the chondrogenic media. Then, they were implanted in nude mice subcutaneously to evaluate for the effect of dynamic compression for regeneration of cartilage. From the biochemical analyses, chondrogenic differentiation was sustained and enhanced significantly and chondral extracellular matrix was increased through mechanical stimulation. Histological analyses showed that implants stimulated mechanically formed mature and well-developed cartilaginous tissue, as evidenced by bone marrow derived chondrocytes within lacunae. Consequently, the periodic application of dynamic compression can encourage bone marrow stromal cells to differentiation to chondrogenic lineage and to maintain their phenotypes.

In cartilage tissue engineering, as a cell source, adult stem cells are very attractive for clinical applications. Recent studies suggest that human adipose tissue-derived stromal cells (ASCs) have multilineage potential similar to bone marrow-derived stromal cells (BMSCs). ASCs are obtained from adipose tissue easily isolated by suction-assisted lipectomy in various body parts. Also, as one of major factors of cartilage tissue engineering, scaffolds have an important role in cartilage formation. Poly(L-lactide-co-ε-carprolactone) scaffolds have physiological activity, biodegradability, high cell affinity, and mechano-activity. The object of this study is cartilaginous tissue formation using highly elastic PLCL scaffolds and ASCs in vitro and in vivo. Poly(L-lactide-co-ε-carprolactone) copolymers were synthesized from lactide and ε-carprolactone in the presence of stannous octoate as catalyst. The scaffolds with 85% porosity and 300-500μm pore size were fabricated by gel-pressing method. ASCs were seeded on scaffolds and cultured for 21days in vitro. Cell/polymer constructs were characterized by reverse transcriptase-polymerase chain reaction for confirming differentiation to chondrocytes onto PLCL scaffolds. Also, for examining cartilaginous tissue formation in vivo, ASCs seeded scaffolds which were induced chondrogenesis for 2 weeks were implanted in nude mice subcutaneously for up to 8weeks. Histological studies showed that implants partially developed cartilaginous tissue within lacunae. And there was an accumulation of sulfated glycoaminoglycans. Immunohistochemical analysis revealed that implants were positively stained for specific extracellular matrix. These results indicate that ASCs and PLCL scaffols could be used to cartilage tissue engineering.

Poly-L-lactic acid (PLLA) is a desirable and very attractive polymer for fabricating porous scaffolds. As of now, a solvent casting method with organic solvents has been used in scaffold fabrication process. However, residual organic solvents in the scaffolds have the problems of decreasing the effect of osteogenic induction due to the hindrance of bioceramic by polymer solution and it’s harmfulness in vivo. To avoid these disadvantages of scaffolds by organic solvent casting method, we developed a new method fabricating polymer (PLLA)/ceramic (β -TCP) composite scaffolds by baking method without using solvent, and then we tested properties of scaffolds on animals. As the result, non-toxicity has been proved through animal experiment and newly fabricated polymer/ceramic composites by a novel sintering method were induced rapid bone regeneration through enhancing the interaction of cells and a bone induction factor without any host immune response.

In this paper, we present a new method for the creation of a smaller dialyzer and do so by incorporating polymeric nanofiber web, which is known to have good filtration efficiency for broad particle sizes, into a poly (dimethylsiloxane)-based microplatform. We have developed a process that makes possible the efficient production of polyethersulfone and polyurethane nanofiber web and that, itself, incorporates an electrospinning method. We have combined the nanofiber web with the PDMS-based microfluidic platform to create a chip-based portable hemodialysis system. With the dialyzing chip, we evaluated the filtration capability of molecules in broad ranges of sizes and compared the filtration capability of nanofiber membranes with that of PES and polyvinylidene fluoride porous membranes (sheet type): we discovered that the nanofiber membranes have better filtration performance than the other membranes. Blood cells were not mechanically affected during their filtration and their transportation through the chip. In conclusion, we have demonstrated the feasibility of chip-based hemodialysis, and we expect that our method suggested in this paper will be applied to the development of small light-weight dialyzers for the realization of portable hemodialysis systems.

Insertion of cannulae into vessels may apply non-physiological load and stress on blood cells, such that adenosine diphosphate may increase and result in hemolysis. Authors used the computational method to simulate the blood flow inside of the cannula. We limited the research to within the drainage cannulae. Nine different cannulae categorized by the number of side holes of 4, 12, and 20, and also categorized by the array type as staggered array, in-line array, and alternative in-line array were studied and compared to the cannulae with no side holes by using computational fluid dynamics. We evaluated the flow rate, the wall shear stress, and the shear rate, and compared them with one another to estimate the effect of the side holes. The flow rate is not proportional to the number of the side holes. However, larger number of side holes can reduce the mean shear rate.

In this study, we developed a wireless monitoring system for outpatients equipped with a moving-actuator type pulsatile bi-ventricular assist device, AnyHeart™. The developed monitoring system consists of two parts; a Bluetooth-based short-distance self-monitoring system that can monitor and control the operating status of a VAD using a Bluetooth-embedded personal digital assistant or a personal computer within a distance of 10 meters, and a cellular network-based remote monitoring system that can continuously monitor and control the operating status of AnyHeart™ at any location. Results of in vitro experiments demonstrate the developed system's ability to monitor the operational status of an implanted AnyHeart™.

In this paper, we describe the development of a self-management protocol for a controller of a moving-actuator type artificial heart, AnyHeart™. The developed protocol analyzes motor current signals and detects abnormal pumping statuses. If preset abnormal pumping statuses are detected by an implemented algorithm, a controller triggers an emergency management procedure and transmits an alarm message to predetermined medical and engineering staffs via a cellular phone network to notify them of an abnormal pumping status occurrence and its likely cause. Results of in vitro performance experiments showed that the developed protocol can detect simulated abnormalities in motor current, manage the operating status of the blood pump during an emergency, and transmit an alarm message as desired.

A new pulsatile extracorporeal life support device (ECLS) has been developed, designed to sustain pulsatile blood flow during emergency cardiopulmonary resuscitations and cardiopulmonary operations. This device features two identical pulsatile pumps that operate alternately and can therefore provide blood inflow in a more uniform manner than similar systems featuring a single-pump configuration. In order to confirm the presumed benefits of this newly-developed dual pulsatile pump configuration, we have conducted a series of in vitro experiments designed to compare the properties of the new system with a single pump system, specifically with regard to pump delivery rate and active filling efficiency. Our results reveal that the dual pump configuration can, indeed, deliver a higher flow than can the single-pump system, and exhibits an active filling efficiency superior to that of the single-pump configuration. We performed a series of animal experiments to measure the pulsatility of the dual-pump configuration in terms of equivalent energy pressure (EEP). In order to measure EEP, we measured femoral arterial pressure and pump outflow. The results of our animal experiments revealed that the newly-developed pulstile ECLS exhibits sufficient pulsatility in terms of the EEP considerations.

Blood flow in the twin-pulse life-support system (T-PLS) pulsatile blood pump was simulated using a three-dimensional rigid body-fluid-solid interaction model. This model can delineate the blood flow in the T-PLS resulting from operation of a moving actuator. The numerical method used in this study was a commercial finite element package called ADINA. We used a contact and fluid-solid interaction model to compute the blood hemodynamics in the sac. Blood flow is generated by the motion of the actuator, which strongly interacts with the solid material surrounding the blood. To obtain basic bioengineering data on the optimum operation of the T-PLS, we simulated four models in which the actuator moved at different speeds and investigated both the flow pattern and the distribution of shear stress. During the contraction phase, a strong axial flow is observed around the outlet, whereas there is stagnant flow around the inlet. The maximum shear stress in each model depends on the operation mode; however, all four models have similar flow rates. The sinusoidal mode exhibited the lowest maximum shear stress and is thus considered the most efficient of the four operating modes.

Rationale and objective To evaluate the ultrasonographic features of breast masses using a computerized scheme and to correlate the feature values with radiologists’ grading. Materials and methods One hundred and seventy-five breast ultrasound images (one to five images per subject) from 61 women (age 17–89 years, mean 43 years) were studied. Thirty-eight of the 157 images were from 11 women with malignant lesions, and the remaining 137 were from 50 patients with benign lesions. Two breast imaging radiologists participated in an observer performance study and were asked to grade, on a scale of 3, shape (1: regular, 3: very irregular), border (1: sharp, 3: ill-defined), internal texture (1: homogeneous, 3: very heterogeneous), width/depth ratio (1: flat, 3: tall), posterior enhancement (1: strong, 3: none), and lateral shadowing (1: strong, 3: none). The computerized scheme analyzed the breast region within a region of interest that was placed by a radiologist and quantified the following parameters: shape (jag count, disperse, convex hull depth, and lobulation count), border (acutance, average maximum ascending gradient, and sigmoid curve fitting), texture (edge density, co-occurrence matrix, and fractal dimension), width-depth ratio, posterior enhancement, and lateral shadowing. Correlations between the radiologists and the computerized scheme for assessing parameters in corresponding categories were computed. Results Good agreement was seen in posterior enhancement ( P r = 0.45), lateral shadowing ( P r = 0.38), width-depth ratio ( P r = 0.33), and shape features (all P r = 0.38), disperseness ( r = 0.55), and convex hull depth ( r = 0.44). The remaining parameters demonstrated a poor or weak correlation ( r Conclusion The radiologists and the computerized scheme correlated best in analysis of shape features and posterior enhancement. We have yet to determine the significance of these features for the implementation of a computer-aided diagnosis program for characterizing breast ultrasound masses.

A pulsatile left ventricular assist device (LVAD) was used to support the aortic blood pumping function of an injured left ventricle, and as a result helped its recovery. It is important to observe a left ventricle's pumping status and to adjust the operating status of a LVAD to reduce the left ventricle's pumping load and thus to enhance its recovery. To observe the left ventricle's pumping status, an electrocardiogram (ECG) signal is generally used because it is a result of the natural heart's blood pumping function. In this paper, we describe the development of an ECG based counterpulsation control algorithm that prevents simultaneous aortic blood co-pumping by a left ventricle and a moving-actuator type pulsatile LVAD and as a result, reduces the natural heart's pumping load. In addition, to verify the algorithm's applicability for LVAD control we designed three ECG based automatic pump control algorithms that use a developed counterpulsation control algorithm. These algorithms control the operating status of a LVAD automatically and, at the same time, maintain a counterpulsing status. The results of in vitro experiments show that the counterpulsing effect between a left ventricle and a LVAD was successfully produced and that the newly designed automatic pump control algorithms met their own control purposes with a counterpulsing effect.

The Moving Actuator type artificial heart(AnyHeart) as well as many other artificial hearts uses a motor as its power source. For controllability of control parameters such as pump rate, pump output, blood pressure profile and flow form, the precise motor speed control is important. However, because the implantable device has limited carrying capacity of hardware components in size and number, applying diverse motor control methods are not possible. In addition, the existing PI (Proportional-Integral) motor controller does not show satisfactory performance. A new controller that is sufficiently robust for the changes of load and physical system parameters has been designed and tested. The robust speed controller is based on the sliding mode control method that is applicable to a system of which the ranges of uncertainty in physical parameters are known. In a mock circulation system test, the actual speed showed good tracking characteristics in respect to the reference speed. Fast follow-up characteristics were also observed under high afterload and speed conditions. The speed error, current and power consumption were reduced by about 40%. The proposed control technique overcomes the limitations of the PI controller, and makes important improvements in both performance and stability.

AnyHeart is a single-piece, implantable biventricular assist device. This electromechanical BVAD has a moving-actuator mechanism. To monitor the status of AnyHeart from anywhere at any time, a portable personal digital assistant (PDA) monitor and web-based remote monitoring system were developed. The PDA local monitoring system has replaced bulky personal computer monitoring systems. The web-based remote monitoring system has several functions such as data collecting, storing, and posting through the internet. Basically, interventricular pressure (IVP) is a parameter indicating the filling level of the blood chambers of AnyHeart. The pump output can be estimated using IVP, which is acquired noninvasively from AnyHeart. With the proposed method, we can estimate the pump output with a small margin of error.

Extracorporeal life support (ECLS) systems have been increasingly applied to groups of patients with cardiorespiratory failure, including pediatric and adult patients with respiratory failure. Current pulsatile ECLS systems use a single pulsatile blood pump that generates a high inlet pressure in the membrane oxygenator. To minimize this high inlet pressure, we have developed a new and improved ECLS system, twin pulse life support (T-PLS). To analyze the advantages of T-PLS, we have compared T-PLS with a single pulsatile ECLS system. An acute heart failure model was constructed by using a pulmonary artery banding technique. Fourteen pigs (22-31 kg) were used, with cardiac outputs of 2.0 l/min and a V/Q ratio set at 1. Cannulae of 28 Fr and 18 Fr were used in the right atrium and aorta, respectively. A polypropylene hollow-fiber membrane oxygenator and four polymer valves 30 mm in diameter were used in the T-PLS system. In the single pulsatile ECLS system, Medtronic Hall monostrut valves were used. To evaluate blood cell trauma in both pulsatile ECLS systems, plasma free hemoglobin (fHb) was measured while the systems were in use. The results show that fHb levels in T-PLS are lower than fHb levels in the single pulsatile ECLS system. There is a possibility that T-PLS could be used as an ECLS system for emergency situations.

A Korean artificial heart (AnyHeart) has been implanted in 29 various animals (52–470 kg) to evaluate hemodynamic performance and electromechanical stability. Most were implantable biventricular assist devices in use. A right thoracotomy approach has been a standard technique of implantation. A preclinical fitting test was also performed to observe anatomical feasibility and to compare surgical techniques in 10 human cadavers. The first case of human application was made as a lifesaving procedure on June 12, 2001.

Flow in the blood sac of the Korean artificial heart is numerically simulated by finite element method. Fluid-structure interaction algorithm is employed to compute the three-dimensional blood flow interacting with the sac material. For verification of the numerical method of fluid-structure interaction, two-dimensional flow in a collapsible channel with initial tension is simulated and the results are compared with numerical solutions from the literature. Incompressible viscous flow and linear elastic solid are assumed for the blood and the sac material in the device, respectively. The motion of the actuator is simplified by a time-varying pressure boundary condition imposed on the outer surface of the sac. Numerical solutions on the unsteady three-dimensional blood flow in the sac are provided for the cactus-type model in this study. During systole, the inlet is closed and the blood sac is squeezed by the action of the prescribed pressure on the surface. During diastole, the sac is filled with the blood coming from the inlet while the outlet is closed. A strong flow to the outlet and a stagnated flow near the inlet are observed during systole. Shear stress distribution is also delineated to assess the possibility of thrombus formation. We also simulate numerically the hemodynamics of "the reversed model" where the inlet and outlet are reversed for surgical convenience. It is observed that a recirculating flow was generated near the inner corner of the sac in the reversed model. To assess the material strength of the sac, the shear stress distribution in the solid material is also presented.

We evaluated various spiculate and jagged margin shape features. These are known to be malignant characteristics in breast sonograms. A total of 79 breast ultrasonograms (60 benign, 19 malignant) containing solid breast nodules were evaluated. To determine the boundary of lesions, Markov random field segmentation was used. Our goal was to classify benign and malignant lesions on the breast sonogram. Our algorithm consisted of two steps: segmentation and classification. In the first step, a breast sonogram was segmented using low resolution and Gaussian-Markov random field. The fuzzy clustering method algorithm was then applied to the preprocessed image to initialize the segmentation. Next, to discriminate benign and malignant tumors three types of lesion characteristics were investigated: jag count, compactness, and acutance. Jag count was calculated based on the derivative of curvature, acutance was defined as gray-level variations across the lesion boundary, and compactness was defined as the ratio of boundary complexity to the enclosed area. Sensitivity of the three boundary features (jag count, compactness, and acutance) was 95.1, 94.1, and 81.1%, respectively, and their specificities were 97.2, 92.0, and 78%, respectively. The jag count performed best among the three boundary features. Our results indicate that computerized analysis of boundary characteristics can be an effective method for classifying solid breast nodules in ultrasonograms as malignant or benign. We found that curvature analysis was the best shape features. The curvature method classifies better than the compactness or acutance methods.

Right and left filling pressures are important parameters in the automatic control of a total artificial heart (TAH) within normal physiologic ranges. Our TAH is composed of a moving actuator, right and left ventricles, and an interventricular space (IVS) enclosed by a semirigid housing. During operation of the TAH, the IVS volume is changed dynamically by the difference between the ejection volume of one ventricle and the inflow volume of the other. We measured the interventricular pressure (IVP) waveform by using a pressure sensor and analyzed the relationship between the IVP and the preload condition. From in vitro and in vivo experiments, we found that the measured filling pressures were linearly related to the negative peak value of the IVP. Additionally, we found that we could use the time interval from actuator start to the positive peak value of the IVP (outflow valve opening) as a useful parameter to estimate the blood filling volume of the diastole ventricle.

In this report, we describe an operative procedure for our implantable 1 piece biventricular assist device (BiVAD) based on a moving actuator mechanism, using an ovine model. Our implantable BiVAD is a volumetric coupled 1 piece unit including right and left blood sacs and an actuator assembly based on the moving actuator mechanism. The BiVAD was controlled by fixed rate control with 75 bpm for the most part. Both the left and the right full ejection modes with the maximum stroke angle were selected to minimize blood stasis in the blood sacs because of low assist flow condition. Three Corriedale sheep were used for the device implantation by a left thoracotomy incision. Cannulation was successfully performed in all cases. Although exposability of the right atrial appendage varied from animal to animal, the insertion of the cannula was easily performed. The cannulas were connected to the pump-actuator assembly in the preperitoneal pocket. All 3 animals survived the experimental procedure. During implantation of the device, in the 1 month survival animal, pump flow was maintained between 2.0 L/min and 2.5 L/min, mean aortic pressure was 90–110 mm Hg, and mean pulmonary artery pressure was 20–30 mm Hg. The left and right atrial pressure were maintained between 0 and 5 mm Hg. In conclusion, this ovine model for implantation of the 1 piece BiVAD can be an effective alternative for testing in vivo biocompatibility of the device although it needs more consideration for anatomical fittability for future human application.

Flow induced shape change is important for spatial interpretation of vascular response and for understanding of mechanotransduction in a single cell. We investigated the possible shapes of endothelial cell (EC) in a mathematical model and compared these with experimental results. The linearized analytic solution from the sinusoidal wavy wall and Stokes flow was applied with the constraint of EC volume. The three dimensional structure of the human umbilical vein endothelial cell was visualized in static culture or after various durations of shear stress (20 dyne/cm2 for 5, 10, 20, 40, 60, 120min). The shape ratio (width: length: height) of model agreed with that of the experimental result, which represented the drag force minimizing shape of stream-lining. EC would be streamlined in order to accommodate to the shear flow environmented by active reconstruction of cytoskeletons and membranes through a drag force the sensing mechanism.

The solar cell as the advanced alternative energy resource was found to be acceptable for increasing battery running time of the totally-implantable artificial heart. A sample of the wireless charging system with solar cell base gives a maximum battery running time around 9 hours and some physical and psychological freedom to the patient. This improvement will assist the application of the implantable artificial heart for a longer period of time and with added convenience to the recipient.

Thirty ng/mm2 lumbrokinase, a potent fibrinolytic enzyme, was immobilized in a Korean type total artificial heart (KORTAH) valve by photoreaction; polyallylamine was used as a photoreactive linker. Lumbrokinase-immobilized polyurethane valves were then fitted to the total artificial hearts of 3 healthy 50 kg lambs. In the control lamb, the valves were untreated; in one other, only valves on the right were treated; and in the remaining animal, only those on the left. Implants were in place for up to 3 days, and cardiac output was 5 L/min. To facilitate thrombus formation, low doses of heparin were administered. In the control lamb, thrombi was observed only in the inlet parts of the valves. In the other 2 experiments, thrombi formed in untreated control valves but not in lumbrokinase treated valves. The grade of thrombus formation in untreated valves was 1.06+/-1.37 versus 0+/-0 in the treated part by one-sided Student's t-test (p < 0.1). After implantation, fibrinolytic activity was only observed in treated valves by fibrin plate methods. The proteolytic activity of the treated valves was 3 times higher than that of untreated valves using the azocasein method. These data show that lumbrokinase treated polyurethane valves lead to decreased thrombus formation in vivo and that their biocompatibility is therefore greater than that of untreated valves.

Aortic pressure (AoP) estimation is a very important study for the artificial heart. In this paper, we developed a AoP estimation model for the moving-actuator type total artificial heart (MH-TAH) that was being developed at Seoul National University Hospital. The proposed model is simple and provides beat-by-beat mean AoP estimation. Moreover, it uses non-invasively acquired signals. Model parameters were adjusted with in vitro data by least mean square (LMS) algorithm. Results showed that the proposed scheme gives a mean estimation error of about 8 (mmHg). This ensures the suitability of the proposed model. The proposed approach can also be applied to the model setup of pulmonary arterial pressure (PAP) estimation by using the symmetric characteristics between AoP and PAP.

A new automatic cardiac output control algorithm for an implantable electromechanical total artificial heart (TAH) was developed based on the analysis of motor current waveform without using any transducer. The basic control requirements of an artificial heart can be described in terms of three features: preload sensitivity, afterload insensivity, and balanced ventricular output. In previous studies, transducers were used to acquire information on the hemodynamic states for automatic cardiac output control. However, such a control system has reliability problems with the sensors. We proposed a novel sensorless automatic cardiac output control algorithm (ACOCA) providing adequate cardiac output to the time-varying physiological demand without causing right atrial collapse, which is one of the critical problems in an active filling device. In vitro tests were performed on a mock circulatory system to assess the performance of the developed algorithm and the results show that the new algorithm satisfied the basic control requirements of the cardiac output response.

Adsorption of proteins (fibrinogen, albumin, and gamma globulin) from plasma onto surface-modified PUs (PU-PEO, PU-SO3, and PU-PEO-SO3) was evaluated. Adsorbed fibrinogen at steady state decreased in the order PU-SO3 > PU > PU-PEO-SO3 > PU-PEO, suggesting that sulfonate groups have specific high affinity to fibrinogen. The intermediate fibrinogen adsorption on PU-PEO-SO3 can be explained by the compensatory effect between the low protein binding affinity of the PEO chain and the high fibrinogen binding affinity of the sulfonate group. In addition, PU-PEO-SO3 showed a very fast fibrinogen adsorption due to the high accessibility of the sulfonate group to fibrinogen by the poly(ethylene oxide) (PEO) spacer. The kinetic profiles of their surfaces showed that as the adsorption time increases, fibrinogen initially adsorbed was decreased and a plateau reached, demonstrating that all the surfaces exhibited the Vroman effect (the fibrinogen displacement phenomenon). PU-PEO showed the least fibrinogen and albumin adsorption among PUs, confirming the known nonadhesive property of PEO chains. It is very interesting that PU-PEO-SO3 exhibited the highest adsorption of albumin and the lowest adsorption of IgG. Therefore, it may be concluded that such adsorption behaviors of proteins to PU-PEO-SO3 contribute to improved blood compatibility.

Potent and novel fibrinolytic enzymes (lumbrokinase [LK]) were extracted from the earthworm, Lumbricus rubellus. These enzymes were very stable and showed greater antithrombotic activity than other currently used fibrinolytic proteins. An LK fraction showing the most potent fibrinolytic activity was immobilized onto a polyurethane (PU) surface to investigate its enzymatic activity and antithrombotic activity. A methanol-extracted PU surface was coated with 3% (wt/vol) maleic anhydride methylvinyl ether copolymer (MAMEC)/tetrahydrofuran (THF) solution, and the surface was incubated in an LK solution/phosphate-buffered saline (PBS, pH 7.4). The surface properties were characterized by attenuated total reflectance-Fourier transform infrared spectroscopy (ATR-FTIR), electron spectroscopy for chemical analysis (ESCA), and dynamic contact angle. The stability of immobilized LK was determined by caseinolytic activity assay and the specificity of immobilized LK on fibrinogen/fibrin was observed by sodium dodecyl sulphate-polyacrylamide gel electrophoresis (SDS-PAGE). The antithrombotic activity of immobilized LK was evaluated using an ex vivo rabbit A-A shunt experiment. LK immobilization was confirmed by ATR-FTIR and ESCA. Immobilized LK demonstrated stable proteolytic activity during various incubation periods. Immobilized LK proteolyzed fibrinogen and fibrin almost specifically, while it hardly hydrolyzed other plasma proteins including plasminogen and albumin. In the ex vivo A-A shunt experiment, the LK-immobilized surface significantly prolonged occlusion time over control surfaces. This is primarily due to the high thrombolytic activity of immobilized LK. In this work, a highly efficient surface modification method on the PU surface was developed, and this LK immobilization technique will be very useful in improving the blood compatibility of blood-contacting devices.

Sulphonated poly(ethylene oxide) (PEO-SO3) and PEO-SO3-grafted polyurethane (PU-PEO-SO3) were prepared by bulk modification and their anticoagulant and heparin-like activities were investigated. Anticoagulant activity measured by activated partial thromboplastin time of PU-PEO-SO3 displayed 2%, whereas that of PEO-SO3 itself reached 14% as compared to free heparin. In addition, the anticoagulant effects of these sulphonated polymers were not due to factor Xa inhibition but mainly thrombin inhibition. From the clotting time measurements using reptilase instead of thrombin and antithrombin III (AT III), PEO-SO3 and PU-PEO-SO3 indicated heparin-like activity which represents both prolonged thrombin time (TT) and normal reptilase time and increased TT in the presence of AT III. Thrombin was also neutralized by sulphonated polymers to a great extent. Therefore, the anticoagulant and heparin-like activities of PEO-SO3 and PU-PEO-SO3 seem to contribute to their improved blood compatibility.

Background/Aims: Extracorporeal blood detoxification strategies aimed at supporting impaired liver function have been explored because of the imbalance between donor organs and waiting patients. A limited number of artificial devices are now available clinically, and these are characterized by the use of multistage adsorption procedures in conjunction with hemodialysis, but these features simultaneously increase system complexity and treatment costs. Methods: The authors developed a simpler strategy for liver dialysis based on the use of a multifunctional filter, which enables plasma separation and perfusion in a single unit. Results: Liver dialysis treatments were successfully performed using the devised unit when bovine blood containing uremic and hepatic toxins was circulated. Removal of the solutes under investigation was significant, and reduction ratios of 78% for urea, 98% for creatinine and 91% for bilirubin were achieved. Plasma free hemoglobin levels were reasonably maintained despite prolonged blood recirculation for 5 h, and platelet, hematocrit and hemoglobin levels remained uniform throughout liver dialysis sessions. Conclusion: The devised liver support unit may offer a straightforward and efficient means of cleansing blood for patients with hepatic failure.

In this paper, a sound spectrum analyzing method was proposed to pre detect malfunctions of implantable artificial organs, such as an electromechanical total artificial heart (TAH) or prosthetic valves, without any percutaneous invasion. For this purpose, a sound detecting device was developed using a high sensitivity condenser microphone with a frequency range of more than 13 kHz. Output signals of this device are sampled at 100 kHz maximally, and sampled data are stored in an IBM PC (SamBo, Korea). To remove environmental noises in the measured sound, an adaptive least-mean square algorithm was employed. Using the squared value of the sound signal, the best position where only sounds from mechanical components can be measured was found. The sound spectrum was obtained by the periodogram spectral estimating method. Experiments were performed with this system, and the results indicated that: 1) by using an adaptive noise cancelling algorithm, a more noise-free signal can be obtained; 2) the harmonics from the mechanical components of a pendulum type electromechanical TAH were approximately 1.3 KHz; 3) a spectral change was observed when we compared the power spectral densities of a normal and failed TAH; 4) the spectral shift to higher harmonics occurred with an increase in heart rate; and 5) the sound propagation properties of tissue were investigated with animal experiments. The method proposed was found to be applicable in the detection of implantable artificial organ mechanical failure by sound spectrum analysis without the need for percutaneous invasion.

Although hemodiafiltration is presumed to be a gold standard for higher convective therapy for kidney failure patients, the repetition of forward and backward filtration during hemodialysis increases the total filtration volume and convective clearance. Hence, the authors describe a new method of enhancing forward filtration and backfiltration. The devised method, named pulse push/pull hemodialysis (PPPHD), is based on the utilization of dual pulsation in a dialysate stream; namely, pulsatile devices in the dialysate stream both upstream (a dialysate pump) and downstream (an effluent pump) of the dialyzer. Fluid management accuracy of the unit was assessed using fresh bovine blood, and its hemodialytic performance was investigated in a canine renal failure model. Forward filtration rates during PPPHD were maintained at the levels of dialysate flow rates. Fluid balancing error was less than ±0.84% of total dialysate volume, when 97.4 ± 1.66L of pure dialysate was circulated for 4 hs. The animal remained stable without any complication. Urea and creatinine reductions were 56.9 ± 1.6 and 52.8 ± 2.3%, respectively, and albumin levels remained uniform throughout treatment. The devised PPPHD unit offers a simple, but efficient strategy of combined simultaneous diffusive and convective solute transport for ESRD patients, without the need for external replacement infusion.

To examine the biostability and calcification-resistance of polyurethanes (PUs), the surface of PU was grafted with hydrophobic perfluorodecanoic acid (PFDA) (PU-PFDA), hydrophilic polyethyleneoxide (PEO) (PU-PEO1000), and further negatively charged sulfonate groups (PU-PEO1000-SO3). An in vivo animal test was conducted by subcutaneous implantation in rats during 2, 4 and 6 months. A scanning electron microscope study demonstrated that the degree of surface cracking on explanted PUs was increased in the following order: PU-PFDA > PU > PU-PEO1000 > PU-PEO1000-SO3. In the results of energy dispersive x-ray analysis and inductively coupled plasma atomic emission spectrometry, the deposition of calcium was found abundantly, but that of phosphorus was hardly in existence in all implanted PUs, suggesting that this calcium compound is not a hydroxyapatite. The calcium contents, regardless of implantation time, were also increased in the same order (PU-PFDA > PU > PU-PEO1000 > PU-PEO1000-SO3). After 6 months implantation, no severe tissue reactions were observed and calcification almost occurred on polymer surfaces in all implants. Such superior biostability and anticalcification of PU-PEO1000-SO3 might be attributed to synergistic effects of its excellent surface smoothness, sulfonate acid (SO3−) groups, nonadhesive and mobile PEO, and the high hydrophilicity and enhanced blood compatibility. Therefore, PU-PEO1000-SO3 is promising as biostable and calcification-resistant biomaterial. © 1993 John Wiley & Sons, Inc.

A variety of experiments of endothelial cell seeding on artificial vessels have been performed. To improve endothelialization, one or two extracellular matrix components have been used as an underlying matrix. Although these methods have succeeded in in vitro experiments, they have not performed well in vivo. In this study, the authors used the whole extracellular matrix (ECM) excreted from fibroblasts as an underlying matrix. Fetal human fibroblasts were cultured on a polyurethane (PU) sheet. After confluence was attained, the cytoskeleton and the nuclei of the fibroblasts were destroyed using Triton-X, mitomycin, and irradiation. Omental microvascular endothelial cells from adult humans were seeded on various supports. After 12 days in culture, the cells were counted. The authors found that the ECM treated by irradiation had the highest cell number. In addition, the cells on this support exhibited the best morphologic appearance. Finally, the authors performed preliminary animal experiments. The PU vessels (inner diameter: 1.5 mm) treated with ECM were implanted in the arteries of rats. After the vessels had been implanted for 5 weeks, the authors found that the surface of the PU vessels were completely covered with endothelial cells. On the basis of these results, the authors conclude that the whole ECM makes a better underlying substrate for the endothelialization of small diameter artificial vessels.

As part of an electromechanical total artificial heart (TAH) program, an integrated transcutaneous energy and information transmission (TEIT) system has been developed. In vivo performance of the developed system was evaluated through a simplified animal model without implant of a TAH. The design features include the small size of the implanted part, and dual coil structure of the external part. In the transcutaneous energy transmission (TET) system based on magnetic induction, the external primary and implanted secondary coils have the shape of a truncated cone, 7.0 and 3.8 cm in diameter, and 23 and 12 turns of Litz wire, respectively. The external coil is driven by a 350 to 410 kHz tuned class E amplifier that has a minimum switching loss of power transistor. In vitro test results using 1 cm thick dog's skin showed a flat total efficiency (DC to DC) of 75% for 20 to 30 W of delivered mean power. In order to achieve bidirectional communication between implanted and external components, a small circuit board containing four light emitting diodes and a photodiode was incorporated in each TET coil facing each other across the skin. Unmodulated optical pulse transmitted digital data (9600 baud, RS-232 protocol) in error free condition through an up to 15 mm thick dog's skin patch accommodated 18 degrees of misalignment. Three subacute in vivo studies were conducted in dogs to evaluate performance of the developed system. The secondary set was implanted in the mild flank region of the dog, and the output was percutaneously connected to the control system to drive the external TAH on the mock circulatory system.(ABSTRACT TRUNCATED AT 250 WORDS)

PU-PEO-SO3 was applied as a coating material over a newly designed Sinkhole bileaflet PU heart valve and a porous PU vascular graft. Performance and biocompatibility were evaluated using an in vivo canine shunt system between the right ventricle and pulmonary artery. The survival periods in three implantations were 14, 24, and 39 days, during which no mechanical failure occurred in any Sinkhole valve or vascular graft. Scanning electron microscopy (SEM) studies demonstrated much less platelet adhesion and thrombus formation on PU-PEO-SO3 grafts than on PU vascular grafts. Cracks in the valve leaflet were occasionally observed on PU surfaces, but not on PU-PEO-SO3. After a 39 day implantation, calcium deposition on vascular grafts was decreased as compared with valve leaflets, and calcification on PU-PEO-SO3 was much lower than on PU. These results suggest that Sinkhole valves and vascular grafts are promising, and PU-PEO-SO3 as a coating material is more blood compatible, biostable, and calcification resistant in vivo than in untreated PU.

The surface compositions and characteristics of perfluorodecanoic acid (PFDA)-grafted polyurethane (PU) were investigated to understand its enhanced blood compatibility. The grafting of PFDA was identified by attenuated total reflectance–Fourier transform infrared (ATR–FTIR). The results from angular-dependent electron spectroscopy for chemical analysis (ADESCA) demonstrated the fluorocarbon enrichment at the outermost layer in PFDA-grafted PU. Static secondary ion mass spectroscopy (SIMS) experiments supported the results drawn from ATR–FTIR and ADESCA data about the surface compositions. Energy-dispersive X-ray analysis (EDXA) data by fluorine mapping also indicated a considerable coverage with fluoroalkyl groups on the PU–PFDA surface. The critical surface tension, γc, of the highly hydrophobic PU–PFDA surface revealed an extremely low value of 6.9 dyn/cm due to the optimal orientation of CF3 groups to the uppermost surface. Therefore, such an inert low-energy surface may contribute to improve blood compatibility of PFDA-grafted PU. © 1993 John Wiley & Sons, Inc.

Fibrinogen adsorptions to surface modified polyurethanes (PU, PU-PEO, and PU-PEO-SO3) were studied from plasma in vitro. PU and PU-PEO surfaces demonstrated that initial adsorption increases with increasing plasma concentration in kinetic profiles and adsorption time in adsorption profiles as a function of plasma concentration, but after the plateau is reached, its adsorption amount decreases as plasma concentration (0.2-2.0%) and adsorption time (1-120 min) increase, respectively. In contrast, PU-PEO-SO3 showed that initial adsorption is almost same regardless of plasma concentration and adsorption time, which is due to the high affinity of surface sulfonate group to fibrinogen. All the surfaces indicated the Vroman effect at about 0.6% plasma concentration; however, the displacement was relatively low. Adsorbed amount of fibrinogen at steady state decreased in the order: PUPU-PEO-SO3PU-PEO, regardless of adsorption time and plasma concentration. The adsorption behavior of PU-PEO-SO3 is attributed to both effect of low binding affinity of PEO chain and high affinity of pendant sulfonate group toward fibrinogen.