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Bae I.-H.,Chonnam National University | Bae I.-H.,Korea Cardiovascular Stent Research Institute | Park I.-K.,Chonnam National University | Park D.S.,Chonnam National University | And 3 more authors.
Journal of Materials Science: Materials in Medicine | Year: 2012

Heparinization of surfaces has proven a successful strategy to prevent thrombus formation. Inspired by the composition of adhesive proteins in mussels, the authors used dopamine to immobilize heparin on a stent surface. This study aimed to assess the thromboresistant and endothelialization effects of dopamine-mediated heparin (HPM) coating on a stent material surface. The HPM was synthesized by bonding dopamine and heparin chemically. Cobalt- chromium (Co-Cr) alloy disks were first placed in the HPM solution and applied to surface stability then underwent thromboresistant tests and human umbilical vein endothelial cells (HUVEC) cytotoxicity assays. The results showed not only thromboresistant activity and a stable state of heparin on the surfaces after investigation with toluidine blue and thrombin activation assay but also proliferation of HUVEC in vitro. Studies on animals showed that the HPM-coated stent has no obvious inflammation response and increasing of restenosis rate compared to the bare metal stent (BMS) indicating good biocompatibility as well as safety in its in vivo application. Moreover, improving the endothelial cell (EC) proliferation resulted in a higher strut-covering rate (i.e., endothelialization) with shuttle-shaped EC in the HPMcoated stent group compared to that of theBMS group. These results suggest that this facile coating approach could significantly promote endothelialization and offer greater safety than the BMS for its much improved thromboresistant property. Moreover, it may offer a platform for conjugating secondary drugs such as anti-proliferative drugs. © Springer Science+Business Media, LLC 2012.


Yoon H.J.,Chonnam National University | Jeong M.H.,Chonnam National University | Jeong M.H.,Korea Cardiovascular Stent Research Institute | Bae J.H.,Konyang University | And 7 more authors.
Korean Circulation Journal | Year: 2011

Background and Objectives: Left ventricular (LV) remodeling is a heterogeneous process, involving both infarcted and non-infarcted zones, which affects wall thickness and chamber size, shape and function. Subjects and Methods: A total of 758 consecutive patients (62.8±2.0 years, 539 males) with acute myocardial infarction (AMI), who were examined by echocardiography at admission and after 6 months. An increase in LV end-diastolic volume index >10% was defined as a progressive LV dilation. They were divided into two groups according to the extent of progressive LV dilatation during 6 months. Group I with progressive LV dilatation (n=154, 61.4±11.0 years, 110 males) vs. group II without LV dilatation (n=604, 64.1±12.0 years, 429 males). Results: The age and gender were no significant differences between two groups. The levels of glucose, creatinine, maximal creatine kinase (CK), CK-MB, troponin T and I were significantly increased in group I than in group II (p<0.05). Low ejection fraction (EF) and high wall motion score index (WMSI) were more common in group I than in group II (p<0.05). The presence of dyslipidemia {odds ratio (OR); 1.559, confidence interval (CI); 1.035-2.347, p=0.03}, low EF less than 45% (OR; 3.328, CI 2.099-5.276, p<0.01) and high WMSI above 1.5 (OR; 3.328, CI 2.099-5.276, p<0.01) were significant independent predictors of progressive LV dilatation by multivariate analysis. Conclusion: Dyslipidemia, decreased systolic function and high WMSI were independent predictors of LV remodeling process in patients with AMI Copyright © 2011 The Korean Society of Cardiology.


Kim J.M.,Chonnam National University | Kim J.M.,Korea Cardiovascular Stent Research Institute | Bae I.-H.,Chonnam National University | Bae I.-H.,Korea Cardiovascular Stent Research Institute | And 18 more authors.
Progress in Organic Coatings | Year: 2015

Polysaccharide, despite its effect, is hard to apply for coating on stent surface because its own properties such as insoluble in water, fragmentation and deactivation easily. The aim of this study was to optimize the coating conditions for fucoidan on a bare metal stent (BMS), and to evaluate the inhibitory effect of a fucoidan-coated stent on in-stent restenosis (ISR). Three different coating approaches were attempted (designated as multi-layer coating, single-layer coating, and dual coating). Unlike other approaches, it was hard to notice the irregular, blotched or the cracks area in the polymer on the BMS surface in dual coating group. And the release of fucoidan was continued to 24 h and inhibits smooth muscle cell proliferation, when compared to the control, with approximately 42.7% at 3 days and 51.3% at 7 days of culture. In animal study using rabbit iliac artery, histopathological restenosis area were smaller in fucoidan-coated group compared to BMS group (38.6%, p = 0.062 in 148. 9 μg/stent, and 40.6%, p = 0.048 in 250 μg/stent of fucoidan coating group at 4 weeks of post-implantation) and a lower degree of strut coverage were shown in the fucoidan-coated stent group, as compared to the BMS group. These results suggest that dual coating is an appropriate method for fucoidan coating on BMS, and its inhibitory effect can be utilized for the suppression of ISR. © 2014 Elsevier B.V.


Bae I.-H.,Chonnam National University | Bae I.-H.,Korea Cardiovascular Stent Research Institute | Lim K.-S.,Chonnam National University | Park J.-K.,Sunchon National University | And 17 more authors.
Journal of Industrial and Engineering Chemistry | Year: 2015

In this study, our own stent designed by Chonnam National University Hospital (designated as CNUH stent) which is considered an elastic behavior as second trial was subjected to mechanical performance tests and in vivo histological analysis. Four commercialized stents (PROMUS Element™, Cypher®, Resolute Integrity, Xience PRIME) stents were employed as control. In the flat plate and compression test for measuring radial force, the lowest (2.40 ± 0.27N) and moderate (31.27 ± 4.84N) performance was shown in CNUH stent compared to others. On the other hand, In the 3-point bending test for measuring flexibility, CNUH stent showed the greatest flexibility (0.46 ± 0.08N) among competitors (range between 0.66 ± 0.03 in Cypher® and 1.14 ± 0.04 Resolute Integrity), In both foreshortening and recoil test, CNUH stent showed reasonable result (2.13 ± 0.15% and 3.29 ± 0.41%, respectively). However, histological analysis showed that CNUH stent has any significant difference to Coroflex® Blue BMS on various parameters. Although the radial force of CNUH stent was slightly lower than that of other products, it showed the greatest performance in its flexibility. It can be utilized for developing drug-eluting stent as a basic structure. © 2014 The Korean Society of Industrial and Engineering Chemistry.


Jang E.-J.,Chonnam National University | Jang E.-J.,Korea Cardiovascular Stent Research Institute | Bae I.-H.,Chonnam National University | Bae I.-H.,Korea Cardiovascular Stent Research Institute | And 12 more authors.
Journal of Materials Science: Materials in Medicine | Year: 2015

The drug-eluting stent still has limitations such as thrombosis and inflammation. These limitations often occur in the absence of endothelialization. This study investigated the effects of WKYMVm- and sirolimus-coated stents on re-endothelialization and anti-restenosis. The WKYMVm peptide, specially synthesized for homing endothelial colony-forming cells, was coated onto a bare-metal stent with hyaluronic acid through a simple dip-coating method (designated HA-Pep). Thereafter, sirolimus was consecutively coated to onto the HA-Pep (designated Pep/SRL). The cellular response to stents by human umbilical-vein endothelial cells and vascular smooth-muscle cells was examined by XTT assay. Stents were implanted into rabbit iliac arteries, isolated 6 weeks post-implantation, and then subjected to histological analysis. The peptide was well attached to the surface of the stents and the sirolimus coating made the surface smooth. The release pattern for sirolimus was similar to that of commercial sirolimus-coated stents (57.2 % within 7 days, with further release for up to 28 days). Endothelial-cell proliferation was enhanced in the HA-Pep group after 7 days of culture (38.2 ± 7.62 %, compared with controls). On the other hand, the proliferation of smooth-muscle cells was inhibited in the Pep/SRL group after 7 days of culture (40.7 ± 6.71 %, compared with controls). In an animal study, the restenosis rates for the Pep/SRL group (13.5 ± 4.50 %) and commercial drug-eluting stents (Xience Prime™; 9.2 ± 7.20 %) were lower than those for bare-metal stents (25.2 ± 4.52 %) and HA-Pep stents (26.9 ± 3.88 %). CD31 staining was incomplete for the bare-metal and Xience Prime™ groups. On the other hand, CD31 staining showed a consecutive linear pattern in the HA-Pep and Pep/SRL groups, suggesting that WKYMVm promotes endothelialization. These results indicate that the WKYMVm coating could promote endothelial healing, and consecutive coatings of WKYMVm and sirolimus onto bare-metal stents have a potential role in re-endothelialization and neointimal suppression. © 2015, Springer Science+Business Media New York.


Lim K.S.,Cardiovascular Convergence Research Center Nominated by Korea Ministry of Health and Welfare | Lim K.S.,Chonnam National University | Park J.-K.,Sunchon National University | Jeong M.H.,Korea Cardiovascular Stent Research Institute | And 29 more authors.
Macromolecular Research | Year: 2016

The aim of this study was to evaluate the optimal method for coating a double-layer polymer coronary stent with sirolimus and alpha-lipoic acid (ALA) in a porcine coronary overstretch restenosis model. Pigs were randomized into three groups, in which the coronary arteries (10 in each group) were stented with a dual-layer stent with an inner layer of ALA and an outer layer of sirolimus (IAOS, n=10), a dual-layer stent with an inner layer of sirolimus and an outer layer of ALA (ISOA, n=10), or a commercial drug-eluting stent (biolimus-eluting stent, BES, n=10). Histopathological analysis was performed 28 days after stenting. There were no significant differences among the three groups in injury and inflammation scores. There were significant differences among the three groups in neointimal area (1.1±0.16 mm2 for IAOS vs. 1.3±0.41 mm2 for ISOA vs. 1.9±0.50 mm2 for BES, p<0.0001), and percentage of stenosis area (21.4±3.08% for IAOS vs. 29.9±7.72% for ISOA vs. 38.2±9.08% for BES, p<0.0001). Regarding the percentage of stenosis area, microcomputed tomography revealed significant differences between the three groups (23.8±3.51% for IAOS vs. 28.9±4.65% for ISOA vs. 36.4±8.07% for BES, p<0.05). Compared with commercial stent placement, both IAOS and ISOA resulted in significant inhibition of neointimal formation in a porcine coronary restenosis model. In addition, IAOS was more effective than ISOA in preventing anti-neointimal hyperplasia after stenting. © 2016 The Polymer Society of Korea and Springer Sciene+Business Media Dordrecht


Bae I.-H.,Korea Cardiovascular Stent Research Institute | Jeong M.H.,Korea Cardiovascular Stent Research Institute | Jeong M.H.,Chonnam National University
Progress in Biomedical Optics and Imaging - Proceedings of SPIE | Year: 2012

Drug-eluting stents (DES) are superior to bare metal stents (BMS) in reducing restenosis rates across a wide range of patients and lesion subsets. This study presented the investigation of one-year clinical follow-up were registered in 52 primary percutaneous coronary intervention sites in Korea, and pre-clinical results of various drug-coated stent fabricating with many other coating approaches on physiological parameters, Based on our clinical study adverse cardiac events were 17.4 % after DES implantation, which was significantly lower compared with 24.9% of BMS implanted patients. As assumption above outcome, it well repays research and development in new DES. Our research group carefully chooses abciximab, alpha-lipoic acid, heparin / dopamine, inhibitors in cell signal cascade were employed as coating drug. These drug candidates were coated on BMS surface by various methods such as TiO2 film deposited by plasma enhanced chemical vapor deposition, ultrasonic sprayer / simple-dip coating, or bio-inspired natural binding technique. In vitro and in vivo results of these new DES fabricated by our research group have showed superior outcomes compare to BMS on physiological parameters such as inflammation score, re-endothelialization, preventing neointema or thrombosis etc. These results are promising safer and more effective to overcome the limitation of DES. © 2012 SPIE.

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