Byoung Goo Min

Plasma protein adsorption to sulfonated poly(ethylene oxide)‐grafted polyurethane surface

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.

Heparin-like anticoagulant activity of sulphonated poly(ethylene oxide) and sulphonated poly(ethylene oxide)-grafted polyurethane.

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.

Differentiation, engraftment and functional effects of pre-treated mesenchymal stem cells in a rat myocardial infarct model.

Background — Mesenchymal stem cells (MSCs) offer a novel therapeutic option in the treatment of acute myocardial infarction. MSCs are able to differentiate into myogenic cells after 5-azacytitdine treatment. However, 5-azacytidine might have genotoxic effects. Recently, it was reported that combined treatment with bone morphogenetic protein-2(BMP-2) and fibroblast growth factor-4(FGF-4) caused cardiac differentiation in non-precardiac mesoderm explants. Therefore, we investigated whether MSCs treated with combined BMP-2 and FGF-4 showed evidence of myogenic differentiation in vitro, and whether these cells resulted in sustained engraftment, myogenic differentiation, and improved cardiac function after implantation in infarcted myocardium. Methods and results — In vitro study: MSCs were treated with BMP-2 + FGF-4 (GF-MSCs) and myogenic phenotype was evaluated immunohistochemically. Cell growth curve was used to compare MSC proliferative capacity between the growth factors and 5-azacytidine treatments. In vivo study: two weeks after coronary artery occlusion, GF-MSCs (n = 15), MSCs (n = 5) labelled with PKH26 were injected into infarcted myocardium. Control animals (n = 5) received a culture medium into the infarcted myocardium.Two weeks after implantation, some engrafted GF-MSCs or MSCs expressed sarcomeric-a-actinin and cardiac myosin heavy chain, as was observed in culture. Echocardiography showed that the GF-MSC group had a better (p < 0.05) left ventricular performance than the other groups. Conclusion — GF-MSCs induced myogenic differentiation in vitro. Moreover, GF-MSCs engrafted into the infarcted myocardium increased myogenic differentiation, prevented dilation of the infarcted region, and eventually improved heart function.

Estimation of Local Cardiac Wall Deformation and Regional Wall Stress from Biplane Coronary Cineangiograms

A new mathematical method was developed to estimate the local epicardial deformation, wall thickness, and the regional circumferential and longitudinal wall stress using biplane coronary cineangiograms. In this method, the motion images of the coronary artery bifurcation points were used as natural landmarks for the kinematic analysis of the ventricular deformation. In four dogs and a normal patients coronary cineangiograms, the estimation results show the validity of the present analysis, compared to the experimental results based upon the implanted markers. Thus, the present method provides a new method of evaluating the regional wall deformation and wall stress together with the blood vessel conditions using the coronary cineangiography procedure.

Cartilaginous tissue formation using a mechano-active scaffold and dynamic compressive stimulation

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-ε-caprolactone) (PLCL) with 85% porosity and 300–500 μm pore size using a gel-pressing method. The scaffold was seeded with 2 × 106 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.

Application of an elastic biodegradable poly(L-lactide-co-ε-caprolactone) scaffold for cartilage tissue regeneration

In cartilage tissue regeneration, it is important that an implant inserted into a defect site can maintain its mechanical integrity and endure stress loads from the body, in addition to being biocompatible and able to induce tissue growth. These factors are crucial in the design of scaffolds for cartilage tissue engineering. We developed an elastic biodegradable scaffold from poly(L-lactideco-ε-caprolactone) (PLCL) for application in cartilage treatment. Biodegradable PLCL co-polymer was synthesized from L-lactide and ε-caprolactone in the presence of stannous octoate as a catalyst. A highly elastic PLCL scaffold was fabricated by a gel-pressing method with 80% porosity and 300–500 μm pore size. The tensile mechanical and recovery tests were performed in order to examine mechanical and elastic properties of the PLCL scaffold. They could be easily twisted and bent and exhibited almost complete (over 94%) recoverable extension up to breaking point. For examining cartilaginous tissue formation, rabbit chondrocytes were seeded on scaffolds. They were then cultured in vitro for 5 weeks or implanted in nude mice subcutaneously. From in vitro and in vivo tests, the accumulation of extracellular matrix on the constructs showed that chondrogenic differentiation was sustained onto PLCL scaffolds. Histological analysis showed that cells onto PLCL scaffolds formed mature and well-developed cartilaginous tissue, as evidenced by chondrocytes within lacunae. From these results, we are confident that elastic PLCL scaffolds exhibit biocompatibility and as such would provide an environment where cartilage tissue growth is enhanced and facilitated.

Preparation and surface properties of PEO-sulfonate grafted polyurethanes for enhanced blood compatibility

In order to improve the thromboresistance of the commercial polyurethane(PU), its surface modification was accomplished by three new different methods and their surface characteristics were investigated using ATR-FTIR, ESCA, SEM, and dynamic contact angle measurements. Sulfonations using propane sultone were performed directly onto PU or onto hydrophobic dodecanediol (DDO) grafted PU or onto hydrophilic poly(ethyleneoxide) (PEO) grafted PU. ESCA data coincided well with ATR-IR results, as more 0 at. % for PEO grafted PUs and the presence of S for the sulfonated PUs were revealed. At SEM observation the surfaces of PU-DDO and PU-PEO were relatively smooth, whereas all the sulfonated PU surfaces showed excellent smoothness and homogeneity. The hydrophilicity of the surfaces was considerably increased after PEO grafting or sulfonation. In addition, all the sulfonated PU surfaces, particularly PU-PEO-SO3, which has further hydrophilicity, exhibited complete wetting behavior due to the negatively charged SO3 groups.

In vivo performance evaluation of a transcutaneous energy and information transmission system for the total artificial heart.

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 dogs 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 dogs 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)

Surface characteristics and blood compatibility of polyurethanes grafted by perfluoroalkyl chains

Polyurethane (PU) surface was chemically modified by grafting of perfluorodecanoic acid (PFDA) to produce a highly hydrophobic surface to compare the blood compatability with hydrophilic poly(ethylene oxide) (PEO) grafted PUs. The advancing contact angle of modified PU-PFDA was increased up to 115 deg, while that of untreated PU was 86 deg. The PFDA grafted PU exhibited less adhesion and shape change of platelets than untreated PU, and the activated partial thromboplastin time (APTT) of PU-PFDA was considerably extended. The ex vivo occlusion time of untreated PU was only 50 min, but that of PFDA grafted PU was extended to 130 min, indicating that this hydrophobic surface is significantly blood compatible. It is interesting to find that the enhanced blood compatibility of very hydrophobic PU-PFDA was equivalent to hydrophilic PU-PEO.

A moving-actuator type electromechanical total artificial heart. II. Circular type and animal experiment

For pt.I see ibid., vol.37, no.12, p.1186-94 (1990). A novel type of electromechanical total artificial heart (TAH) based on a circular rolling cylinder mechanism was developed to overcome critical problems in motor-driven artificial hearts, such as large size and difficulties in fitting the heart to atrial remnants and arterial vessels. Its performance and reliability were evaluated in mock circulation and in an animal implant experiment. The total weight and volume of the pump are 650 g and 600 mL, respectively. This pump was implanted in a calf for total heart replacement and 96 h of survival was achieved. The whole system, including pump, controller, and control algorithm performed well enough to improve the prospect of eventual clinical application of this TAH system.<<ETX>>