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Biomedical subjects

K D Park

Publications and source records attributed to K D Park.

At least 37 records · Page 2Linked to original sources

Tissue engineering of urinary organs.

Tissue engineering can serve as an alternative treatment for a malfunctioning or lost organ. Isolated and expanded cells adhere to a temporary scaffold, proliferate, and secrete their own extracellular matrices (ECM) replacing the biodegrading scaffold. The genitourinary system, composed of the kidney, ureter, bladder, urethra, and genital organs, is exposed to a variety of possible injury sites from the time of fetal development. All the urinary organs are mainly composed of smooth muscle and uroepithelial cells and which may be approached by tissue engineering techniques. A large number of materials, including naturally-derived and synthetic polymers have been utilized to fabricate prostheses for the genitourinary system. Usually, whenever there is a lack of native urologic tissue, reconstruction is considered with native non-urologic tissue, such as, gastrointestinal segments, or skin or mucosa from multiple body sites. Engineering tissues using selective cell transplantation may provide a means to create functional new genitourinary tissues. This review concerns urinary tissues reconstructed with bladder uroepithelial cells and smooth muscle cells (SMCs) implanted on biodegradable polymer matrices.

Animals↗

Cloning and characterization of the promoter region of the Wilson disease gene.

Wilson disease (WD), an autosomal recessive disorder of copper transport, is marked by impaired biliary excretion and incorporation of copper into ceruloplasmin. Molecular mechanism regulating the expression of the WD gene was studied. We isolated, sequenced, and characterized approximately 1.3 kb of the 5'-flanking region of the WD gene from the human genomic library. The approximately 1.3 kb of the WD sequence directed high level of luciferase activity in HepG2 cells. Interestingly, the 5'-flanking region contained four metal response elements (MREs) and six MRE-like sequences (MLSs), usually found in the metallothionein genes. It also contained a number of putative regulatory elements such as Sp1, AP-1, AP-2, and E-box, but lacked TATA box. The transcription start site was located at 335 base pairs upstream of the translation initiation site. Successive 5'-deletion analyses suggested that the 159-base pair region from -811 to -653, which includes MLS2 (-802 to -796) and MLS3 (-785 to -779), contained one or more positive regulatory element(s). A negative element was also identified at region -1038 to -812. A protein-MLS complex was identified through electrophoretic mobility shift and competition assay using MLS2/MLS3 and HepG2 cell nuclear proteins.

Amino Acid Sequence↗

PDMS-based polyurethanes with MPEG grafts: synthesis, characterization and platelet adhesion study.

Polyurethane (PU), based on poly(dimethyl siloxane) (PDMS) as a soft segment, with monomethoxy poly(ethylene glycol) (MPEG) grafted onto it, was synthesized as a new polymeric biomaterial for coating PDMS-based biomedical devices. Two different chain extenders, ethylene glycol (EG) and diethyl bis(hydroxymethyl) malonate (DBM), were used for the synthesis of PDMS-based PUs and then MPEG was grafted onto them by allophanate and esterification reactions, respectively. Their molecular structures were confirmed qualitatively and quantitatively using FT-IR and 1H-NMR measurements. PDMS-based PU was more hydrophobic than Pellethane, which is a commercial biomedical-grade poly(ether urethane), due to the PDMS-rich phase at the polymeric surface. However, the incorporation of MPEG in PDMS-based PU induced an increase in hydrophilicity. Analyses of their morphology using dynamic mechanical analysis and differential scanning calorimetry showed that the degree of phase separation increased with the content of hard segments. It also showed that MPEG is compatible with a hard segment consisting of 4,4'-diphenylmethane diisocyanate (MDI) and DBM, while being incompatible with one consisting of MDI and EG. Platelet adhesions with PDMS-based PUs were significantly reduced when compared with Pellethane. It was also observed from a platelet adhesion experiment that the incorportion of MPEG further reduced platelet adhesion. PDMS-based PUs with MPEG grafts, which have few hard segments and a distinct PEG phase, exhibited the least platelet adhesion among the polymer samples tested.

Biocompatible Materials↗

The effects of peripheral leukocytes on the hippocampal neuronal changes in transient global ischemia and unilateral cerebral hemispheric infarction.

The participation of activated leukocytes and subsequent production of chemical mediators has been well accepted in the pathophysiology of hypoxic-ischemic injury. This study was performed to see the effects of leukocytes on hippocampal neuronal damage in transient global ischemia induced by 10-min occlusion of bilateral common carotid arteries (CCAs) with reperfusion for various times, and in complete unilateral ischemia induced by 24-hr ligation of left CCA. Leukopenia was induced by intraperitoneal injection of cyclophosphamide for 4 days. The results showed that hippocampal neuronal damages were worse at 6-hr reperfusion in leukopenic experimental group than in the control group. In comparison, 24-hr and 3-day reperfusion leukopenic groups showed less numbers of damaged neurons and milder changes. The 5-day reperfusion group showed inconsistent changes. Unilateral CCA occlusion showed extensive infarction in 83.3% of gerbils in the control group, compared to 25% of gerbils in the experimental group (p<0.05). These results strongly suggest that the number of peripheral leukocytes were closely related to the development of delayed neuronal damage of hippocampus in transient global ischemia and the incidence of infarction induced by 24-hr unilateral CCA ligation.

Animals↗

Clinical analysis of 12 Korean Lambert-Eaton myasthenic syndrome (LEMS) patients.

The Lambert-Eaton myasthenic syndrome (LEMS) heralds the occurrence of malignancy, especially small-cell lung cancer (SCLC), but it can also occur in the absence of cancer. Twelve patients were diagnosed as LEMS by clinical features and the classical electrophysiological triad, which includes a low amplitude of compound muscle action potentials (CMAP), decremental responses on low-rate stimulation, and incremental responses on high-rate stimulation on the repetitive nerve stimulation (RNS) test. There were 6 male and 6 female patients, ranging in age from 49 to 66 years. Malignancy(all were SCLC) was found in 7 patients. Males predominantly expressed the paraneoplastic form; whereas the primary autoimmune form was found only in women, who showed a good response to corticosteroid treatment. The neurological features were similar in both groups: proximal lower limb weakness, depressed muscle stretch reflexes, and dryness of mouth in nearly all patients. Bulbar dysfunction and limb paresthesia were a little more frequent in the paraneoplastic form. In RNS tests, the characteristic electrophysiological abnormalities were found in all patients and were more profound in the paraneoplastic form. We concluded that LEMS is commonly associated with malignancy, especially SCLC, but it should also be stressed that there are many female LEMS patients who do not harbor any malignancy at all, and that other treatment strategies such as immunotherapy should be considered for these patients.

Aged↗

Interfacial strength between molded UHMWPE and PMMA-MMA monomer treated UHMWPE.

To solve aseptic loosening of cemented acetabular cup and tibial plateaus of hips and knee joint prostheses in total joint replacement, adhesion between the polymeric prostheses made of ultra-high molecular weight polyethylene (UHMWPE) and bone cement made of polymethyl-methacrylate (PMMA) has been investigated. Previous studies using xylene, PMMA, and MMA monomer solution to treat bulk surfaces of UHMWPE resulted in 11.5 +/- 0.65 MPa as the maximum interfacial strength between the treated UHMWPE and bone cement. The present study eliminates the use of xylene; instead, UHMWPE powders were treated with MMA monomer and PMMA-MMA solution, dried, and then compression-molded with untreated UHMWPE powders. The interfacial tensile strengths were measured and the best molding conditions investigated by varying temperature, pressure, and time. Temperature was the predominant factor when compared to that of pressure or time. The maximum interfacial strength between the treated UHMWPE and untreated UHMWPE was 16.3 +/- 0.94 MPa with the molding conditions of 166.5 degrees C, 38.7 MPa, and 1 h. Scanning electron microscopic (SEM) pictures show the coating of the nodules and fibrils of UHMWPE powder with PMMA. Pulled out aggregated nodular space and coated PMMA after fracture could be seen easily from PMMA-MMA treated UHMWPE powder.

Acetabulum↗

Platelet adhesion onto segmented polyurethane surfaces modified by PEO- and sulfonated PEO-containing block copolymer additives.

Polyethylene oxide (PEO) surfaces were prepared by the addition of PEO- and sulfonated PEO-containing amphiphilic block copolymers as surface-modifying additives in a segmented polyurethane (PU). PEO-PPO-PEO triblock copolymers (Pluronics) with different PEO chain lengths (from 2 to 80) were used as additives. The prepared film surfaces were characterized by the measurement of dynamic water contact angles and electron spectroscopy for chemical analysis. It was observed that the PU films containing 10 wt% of PEO additives were surface-saturated with the additives regardless of their PEO chain length, but the PEO chains were more projected from the film surfaces containing the additives with longer PEO chains. The water absorption of the films increased largely with the increasing PEO chain length of the additives. The addition of PEO additives produced film surfaces that were in a gel-like state. The films demonstrated some extraction of the PEO additives. However, the additives with higher molecular weights were entrapped more stably into the PU matrix. The mechanical properties (tensile strength and elongation) of the films were changed by the addition of PEO additives, but the differences were not significant compared to the control PU. The platelet adhesion on the film surfaces decreased with increasing PEO chain length of the additives. The film surface containing additives with long PEO chains (chain length of 80) was particularly effective in preventing platelet adhesion. The effect of negatively charged sulfonate groups on the prevention of platelet adhesion appeared only on the film surfaces containing additives with short PEO chains. For longer PEO chains, the chain mobility effect was more dominant than the negative charge effect on the prevention of platelet adhesion.

Animals↗

Surface characteristics and biocompatibility of lactide-based poly(ethylene glycol) scaffolds for tissue engineering.

Novel lactide-based poly(ethylene glycol) (PEG) polymer networks (GL9-PEGs) were prepared by UV copolymerization of a glycerol-lactide triacrylate (GL9-Ac) with PEG monoacrylate (PEG-Ac) to use as scaffolds in tissue engineering, and the surface properties and biocompatibility of these networks were investigated as a function of PEG molecular weight and content. Analysis by ATR-FTIR and ESCA revealed that PEG was incorporated well within the GL9-PEG polymer networks and was enriched at the surfaces. From the results of SEM, AFM, and contact angle analyses, GL9-PEG networks showed relatively rough and irregular surfaces compared to GL9 network, but the mobile PEG chains coupled at their termini were readily exposed toward the aqueous environment when contacting water such that the surfaces became smoother and more hydrophilic. This reorientation and increase in hydrophilicity were more extensive with increasing PEG molecular weight and content. As compared to GL9 network lacking PEG, protein adsorption as well as platelet and S. epidermidis adhesion to GL9-PEG networks were significantly reduced as the molecular weight and content of PEG was increased, indicating that GL9-PEG networks are more biocompatible than the GL9 network due to PEG's passivity. Based on the physical and biological characterization reported, the GL9-PEG materials would appear to be interesting candidates as matrices for tissue engineering.

Bacterial Adhesion↗

Sulfonated poly(ethylene oxide)-grafted polyurethane copolymer for biomedical applications.

Sulfonated poly(ethylene oxide) (PEO-SO3)-grafted polyurethane (PU) copolymer (PU-PEO-SO3) was developed for utilization as a material for biomedical applications. Its bulk properties and biocompatibility were investigated and the results were compared to those of PU and PU-PEO (not sulfonated). PU-PEO-SO3 copolymer showed higher water uptake than PU and PU-PEO, indicative of increased hydrophilicity due to the grafting of PEO-SO3. Compared with PU, PU-PEO-SO3 displayed lower glass transition temperature (Tg) and melting endotherm from DSC analysis, suggesting the increase of microphase separation and the suppression of hard-segment packing. PU-PEO-SO3 had practically similar mechanical properties to PU, indicating that the chemical modification of PU was accomplished without reducing its bulk properties. From the results of biocompatibility tests, PU-PEO-SO3 copolymer showed significantly lower adhesion of platelets and S. epidermidis than PU control and PU-PEO. In addition, the platelet factor 4 (PF4) released from platelets was the lowest in PU-PEO-SO3 among the test materials. PU-PEO-SO3 copolymer, which has excellent mechanical properties and biocompatibility, is expected to be useful as coating, molding, and blending materials for artificial organs and medical devices.

Alkanesulfonates↗

Novel anti-calcification treatment of biological tissues by grafting of sulphonated poly(ethylene oxide).

Biological porcine tissue was modified by the direct coupling of sulphonated poly(ethylene oxide) (PEO-SO3) containing amino acid end groups after glutaraldehyde fixation. The calcification of the modified tissue [bioprosthetic tissue (BT)-PEO-SO3] and control (BT control) was investigated by in vivo rate subdermal, canine aorta-illiac shunt and right ventricle-pulmonary artery shunt implantation models. Less calcium deposition of BT-PEO-SP3 than of BT control was observed in in vivo tests. Such a reduced calcification of BT-PEO-SO3 can be explained by decreases of residual glutaraldehyde groups, a space filling effect and, therefore, improved biostability and synergistic blood-compatible effects of PEO and SO3 groups after the covalent binding of PEO-SO3 to tissue. This simple method can be a useful anti-calcification treatment for implantable tissue valves.

Animals↗

Enhancement of thermostability and catalytic efficiency of AprP, an alkaline protease from Pseudomonas sp., by the introduction of a disulfide bond.

A site-directed mutagenesis in AprP, an alkaline protease isolated from Pseudomonas sp. KFCC 10818 was carried out in order to obtain increased thermostability. Sites for cysteine substitutions to form disulfide bond within AprP were chosen by comparing the sequences with aqualysin I, an alkaline thermostable serine protease whose disulfide bonds seems to be important for its thermostability. Gly199 and Phe236 residues were each replaced with cysteine by site-directed mutagenesis. The G199C/F236C mutant enzyme appeared to form a disulfide bond spontaneously during its expression. It also showed improved kinetic parameters for the hydrolysis of a synthetic peptide substrate at pH 8.5 and 10.5 compared to those of the wild-type enzyme. The half-life of the G199C/F236C mutant was found to be 2 to 4.8 times longer than that of wild-type under various experimental conditions, except when tested under reducing condition, where no significant differences in the half-life of the two types were observed. Therefore, it is concluded that the introduction of the disulfide bond enhanced the thermostability and the catalytic efficiency of the enzyme AprP.

Alkaline Phosphatase↗

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.

Adsorption↗

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.

Anticoagulants↗

Extensive aberrant Mongolian spot.

A 9-month-old male infant had generalized diffuse blue-gray pigmentation over most of his body, sparing the scalp, face, neck, palms, soles, periumbilical area, genital area, and nipples. Within the lesion, there were several conspicuous macules of considerably darker hue. Histologic examination revealed numerous dermal melanocytes. By 16 months of age, the child's blue-gray pigmentation had decreased substantially.

Biopsy↗

Disseminated epidermolytic acanthoma with disseminated superficial porokeratosis and verruca vulgaris in an immunosuppressed patient.

A 40-year-old man who had received long term immunosuppressive treatment for 14 years following kidney transplantation developed multiple skin lesions on both antecubital fossae, scalp, and both lower extremities. Histopathologic findings from three skin regions revealed characteristic features of epidermolytic hyperkeratosis, verruca vulgaris, and disseminated superficial porokeratosis, respectively. Although immunocompromised individuals may demonstrate verruca vulgaris or porokeratosis, disseminated epidermolytic acanthoma (DEA) has not been reported to be associated with immunosuppressed status. We suggest that immunosuppression may play a role in the pathogenesis of DEA, as shown in our case.

Adult↗

In vivo biostability and calcification-resistance of surface-modified PU-PEO-SO3.

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.

Animals↗

Adsorption behavior of fibrinogen to sulfonated polyethyleneoxide-grafted polyurethane surfaces.

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: PU > PU-PEO-SO3 > PU-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.

Adsorption↗