scholarly journals Hierarchical Capillary Coating to Biofunctionlize Drug-Eluting Stent for Improving Endothelium Regeneration

Research ◽  
2020 ◽  
Vol 2020 ◽  
pp. 1-14
Author(s):  
Jing Wang ◽  
Yunfan Xue ◽  
Jun Liu ◽  
Mi Hu ◽  
He Zhang ◽  
...  
Keyword(s):  
Real Time ◽  
Medical Devices ◽  
Drug Eluting Stent ◽  
Vascular Endothelial ◽  
Competitive Growth ◽  
Capillary Coating ◽  
Stent Restenosis ◽  
Solid Region ◽  
Drug Eluting ◽  
Endothelial Growth Factor

The drug-eluting stent (DES) has become one of the most successful and important medical devices for coronary heart disease, but yet suffers from insufficient endothelial cell (EC) growth and intima repair, eventually leading to treatment failure. Although biomacromolecules such as vascular endothelial growth factor (VEGF) would be promising to promote the intima regeneration, combining hydrophilic and vulnerable biomacromolecules with hydrophobic drugs as well as preserving the bioactivity after harsh treatments pose a huge challenge. Here, we report on a design of hierarchical capillary coating, which composes a base solid region and a top microporous region for incorporating rapamycin and VEGF, respectively. The top spongy region can guarantee the efficient, safe, and controllable loading of VEGF up to 1 μg/cm2 in 1 minute, providing a distinctive real-time loading capacity for saving the bioactivity. Based on this, we demonstrate that our rapamycin-VEGF hierarchical coating impressively promoted the competitive growth of endothelial cells over smooth muscle cells (ratio of EC/SMC~25) while relieving the adverse impact of rapamycin to ECs. We further conducted the real-time loading of VEGF on stents and demonstrate that the hierarchical combination of rapamycin and VEGF showed remarkable endothelium regeneration while maintaining a very low level of in-stent restenosis. This work paves an avenue for the combination of both hydrophobic and hydrophilic functional molecules, which should benefit the next generation of DES and may extend applications to diversified combination medical devices.

Abstract 13044: Serum Vascular Endothelial Growth Factor-C Levels are Inversely Associated with the Risk of Cardiac and Cerebrovascular Events Following Drug-eluting Stent Implantation

Circulation ◽  
2014 ◽  
Vol 130 (suppl_2) ◽  
Author(s):  
Takashi Unoki ◽  
Hiromichi Wada ◽  
Masaharu Akao ◽  
Shuichi Ura ◽  
Akira Yamada ◽  
...  
Keyword(s):  
Vascular Endothelial Growth Factor ◽  
Growth Factor ◽  
Drug Eluting Stent ◽  
Vascular Endothelial ◽  
Cox Proportional Hazard ◽  
Cerebrovascular Events ◽  
Drug Eluting ◽  
Factor C ◽  
Endothelial Growth Factor

Background: Vascular endothelial growth factor-C (VEGF-C) plays a key role in lymphangiogenesis. Recently, we demonstrated that VEGF-C is closely associated with dyslipidemia and atherosclerosis. However, the prognostic value of VEGF-C levels after drug-eluting stent (DES) implantation is unknown. Methods and Results: We performed a prospective cohort study involving a total of 443 patients (age, 71.7±9.0 y [SD]; male, 73.8%; number of lesions, 1.6±0.8) who underwent successful DES implantation. Patients were recruited between January 2010 and October 2013, and were followed up over 3 years. The primary outcome was major adverse cardiac and cerebrovascular events (MACCE) defined as cardiovascular death, hospitalization due to acute coronary syndrome, stroke, heart failure, and coronary revascularization. The median follow-up was 617 (inter-quartile range, 320-937) days. Pre-procedural serum levels of high-sensitivity C-reactive protein (hsCRP), vascular endothelial growth factor-A (VEGF-A), and VEGF-C were measured. During the follow-up period, MACCE developed in a total of 106 patients (23.9%). Patients were divided into two groups based on the median of each biomarker. In Kaplan-Meier analyses, low-VEGF-C (P=0.0005 by log-rank test), but not high-hsCRP (P=0.3) or high-VEGF-A (P=0.3), was significantly associated with the risk of MACCE. Multivariate Cox proportional hazard analyses revealed that levels of VEGF-C (hazard ratio [HR], 0.77 per 1-SD increase; 95% confidence interval [CI], 0.62-0.94; P=0.011), but not hsCRP (HR, 1.05; 95% CI, 0.86-1.25; P=0.6) or VEGF-A (HR, 1.04; 95% CI, 0.86-1.23; P=0.6), were inversely and significantly associated with MACCE after adjustment for age, gender, and established risk factors, the number of lesions, and type of DES. Finally, we performed stepwise multivariate Cox proportional hazard analysis including data on age, gender, established risk factors, the number of lesions, type of DES, and VEGF-C levels. Notably, the only independent predictor of MACCE was the VEGF-C level (HR, 0.74 per 1-SD increase; 95% CI, 0.61-0.91; P=0.0042), followed by diabetes (HR, 1.47; 95% CI, 0.98-2.21; P=0.060). Conclusions: A low VEGF-C value may serve as a predictor of MACCE after DES implantation.

scholarly journals Mutual influence of incorporated drugs in a dual drug delivery coating for cardiovascular applications

2017 ◽  
Vol 3 (2) ◽  
pp. 379-382
Author(s):  
Katharina Wulf ◽  
Michael Teske ◽  
Claudia Matschegewski ◽  
Daniela Arbeiter ◽  
Thomas Eickner ◽  
...  
Keyword(s):  
Drug Delivery ◽  
Mutual Influence ◽  
Local Drug Delivery ◽  
Drug Eluting Stent ◽  
Vascular Endothelial ◽  
Effective Inhibition ◽  
Drug Eluting ◽  
The Stability ◽  
Endothelial Growth Factor

AbstractFor a long-term efficient drug-eluting stent for vascular applications, the development of drug-loaded coating, combining the effective inhibition of smooth muscle cell proliferation while promoting the re-endothelialization, is a promising concept. However the mostly required simultaneous incorporation of drugs can influence decisively the stability, efficacy and release of the respective drug. Therefore, the mutual influence of a dual local drug delivery coatings based on poly(L-lactide-co-ε-caprolactone) (PLLA-co-CL) containing vascular endothelial growth factor (VEGF165) coupled to the surface and an embedded drug, such as fluorescein diacetate (FDAc) instead of Paclitaxel (PTX) on the in vitro drug release was investigated. Surprisingly, for the investigated coating the immobilized VEGF loading was enhanced and the release profile was accelerated by FDAc incorporation. Even a manifold increase for the in vitro released amounts of VEGF was detected. In contrast, the immobilization of VEGF seems to have a negligible influence on the in vitro FDAc release profiles.

Abstract 17849: Serum Vascular Endothelial Growth Factor Levels Associated With the Risk of Major Adverse Cardiac and Cerebrovascular Events After Drug-eluting Stent Implantation

Circulation ◽  
2015 ◽  
Vol 132 (suppl_3) ◽  
Author(s):  
Takashi Unoki ◽  
Daisuke Takagi ◽  
Kensuke Takabayashi ◽  
Suichi Ura ◽  
Akira Yamada ◽  
...  
Keyword(s):  
Vascular Endothelial Growth Factor ◽  
Growth Factor ◽  
Drug Eluting Stent ◽  
Vascular Endothelial ◽  
Proportional Hazard ◽  
Coronary Syndrome ◽  
Cox Proportional Hazard ◽  
Cerebrovascular Events ◽  
Drug Eluting ◽  
Endothelial Growth Factor

Background: Vascular endothelial growth factor (VEGF), a central player in angiogenesis, is not only involved in the progression of atherosclerotic plaque, but also required for preventing decompensated heart failure (HF). High circulating oxidatively modified LDL-cholesterol (oxLDL) levels are associated with vulnerability to the rupture of atherosclerotic lesions. However, the relationships of circulating VEGF and oxLDLs with major adverse cardiac and cerebrovascular events (MACCE) in patients undergoing coronary drug-eluting stent (DES) implantation are unclear. Methods and Results: We enrolled 441 patients who electively underwent coronary DES implantation. Patients were followed up over 2 years. MACCE were defined as cardiac and cerebrovascular death, acute coronary syndrome, stroke, and HF hospitalization. Revascularization for asymptomatic patients were excluded. Pre-procedural serum levels of high-sensitivity CRP (hsCRP), VEGF, and two oxLDLs, serum-amyloid-A/LDL complex (SAA-LDL) and α1-antitrypsin/LDL complex (AT-LDL), were measured. During a median follow-up of 720 (IQR, 498-720) days, MACCE developed in a total of 39 patients (8.8%). Patients were divided into two groups based on the median of each biomarker. In Kaplan-Meier analyses, high-VEGF and high-SAA-LDL ( P =0.009, P =0.0498 by log-rank test, respectively), but not high-hsCRP or high-AT-LDL, were significantly associated with MACCE. Multivariate Cox proportional hazard analyses revealed that natural log-transformed VEGF levels (Ln-VEGF) (HR, 1.9 per 1 SD increase; 95% CI, 1.3 to 3.0; P =0.001), but not Ln-SAA-LDL (HR, 1.2; 95% CI, 0.89-1.5, P =0.3), Ln-hsCRP, or Ln-AT-LDL, was significantly associated with MACCE after adjustment for age, sex, and established risk factors. Finally, we performed stepwise multivariate Cox proportional hazard analysis including possible confounders, such as the number of lesions and type of DES, and these biomarkers. Notably, the independent predictors of MACCE were age (HR, 1.8 per 10 years; 95% CI, 1.2-2.7; P =0.004), Ln-VEGF (HR, 1.9; 95% CI, 1.2-3.1; P =0.005) and chronic kidney disease (HR, 2.5; 95% CI, 1.2-5.0; P =0.01). Conclusions: A high VEGF value may serve as a predictor of MACCE following coronary DES implantation.

scholarly journals TCTAP A-030 Drug Coated Balloon Versus Drug-eluting Stent for In-stent Restenosis After Drug-eluting Stent Implantation: A Meta-analysis

2021 ◽  
Vol 77 (14) ◽  
pp. S19
Author(s):  
Hendy Bhaskara Perdana Putra ◽  
Quri Meihaerani Savitri ◽  
Wally Wahyu Mukhammad ◽  
Atiyatum Billah ◽  
Alan Dharmasaputra ◽  
...  
Keyword(s):  
Stent Implantation ◽  
Meta Analysis ◽  
Drug Eluting Stent ◽  
Stent Restenosis ◽  
Drug Eluting ◽  
Drug Coated Balloon ◽  
In Stent Restenosis

scholarly journals Polarization-sensitive OFDI findings of vascular tissue response following drug-eluting stent implantation in patients with coronary artery disease

2020 ◽  
Vol 41 (Supplement_2) ◽  
Author(s):  
K Otsuka ◽  
M Villiger ◽  
L.J.C Van Zandvoort ◽  
T Neleman ◽  
A Karanasos ◽  
...  
Keyword(s):  
Clinical Decision Making ◽  
Vascular Tissue ◽  
Clinical Decision ◽  
Estimating Equation ◽  
Tissue Response ◽  
Drug Eluting Stent ◽  
Funding Source ◽  
National Budget ◽  
Stent Restenosis ◽  
Drug Eluting

Abstract   Intravascular polarimetry (IVP) with polarization-sensitive (PS-) optical frequency domain imaging (OFDI) measures polarization properties of the coronary arterial wall in parallel with the conventional OFDI images (Figure 1A). Tissues rich in collagen and smooth muscle cells (SMCs) appear birefringent, while the presence of lipid and macrophages causes depolarization. Because drug-eluting stents (DES) are designed to prevent SMC proliferation and collagen deposition, we hypothesized that neointimal tissue would exhibit low birefringence. The accumulation of lipid-laden macrophages characteristic of neoatherosclerosis should result in notable depolarization. Methods This study included 19 DES imaged with PS-OFDI in 13 patients (median follow-up period of 1.5 years). Coronary segments stented >90 days were analyzed every 1 mm. We analyzed polarization properties of the neointima in a total of 455 frames, and in additional 97 frames of native atherosclerosis remote from the stented segments. Neointima, delineated by the lumen and the inner boundary of the stent, was manually segmented in the intensity images using MATLAB. The median birefringence in all areas of the segmented neointima featuring a depolarization of ≤0.2 and the median depolarization across the entire neointima were computed for each frame after masking the guidewire shadow. Frames presenting intensity features of macrophages, lipid or calcifications extending to at least one adjacent frame were classified as neoatherosclerosis (n=112), and otherwise as normal neointima (n=343). For comparison with neoatherosclerosis, polarization properties of native atherosclerosis (n=97) were measured. We also categorized all frames of a stented segment according to the presence of in-stent restenosis (ISR) and/or stent thrombosis (ST) (204 frames from 5 patients). A generalized linear model using a generalized estimating equation or one-way ANOVA was used for statistical analysis. Results The major findings of the present study are: 1) neoatherosclerosis exhibited lower birefringence than native atherosclerosis (p<0.001, Figure-1B); 2) depolarization was positively associated with neoatherosclerosis (β=0.86, p<0.001) and ISR/ST (β=0.72, p=0.002), while birefringence was not (Figure 1C); 3) birefringence was positively correlated with the duration after DES implantation (β=5.22×10–3, p<0.001, Figure 1D). For the detection of neointimas within stents with ISR, the best cut-off value for depolarization was 0.033 with a sensitivity of 77% and a specificity of 57% (AUC=0.72). For comparison, using only conventional OFDI parameters to detect stents with ISR, the AUC were 0.52 for calcium area, 0.62 for lipid arc, and 0.63 for macrophage accumulations. Conclusions This study suggests that IVP provides quantitative assessment of vascular healing after DES implantation and may help clinical decision making in patients at high risk of stent failure. Figure 1 Funding Acknowledgement Type of funding source: Public grant(s) – National budget only. Main funding source(s): This work was supported by the National Institutes of Health.

scholarly journals Long-Term Efficacy and Safety of Paclitaxel-Eluting Balloon for the Treatment of Drug-Eluting Stent Restenosis

2015 ◽  
Vol 8 (7) ◽  
pp. 877-884 ◽  
Author(s):  
Sebastian Kufner ◽  
Salvatore Cassese ◽  
Marco Valeskini ◽  
Franz-Josef Neumann ◽  
Stefanie Schulz-Schüpke ◽  
...  
Keyword(s):  
Drug Eluting Stent ◽  
Efficacy And Safety ◽  
Term Efficacy ◽  
Stent Restenosis ◽  
Drug Eluting

scholarly journals Late Restenosis After Paclitaxel-Coated Balloon Angioplasty Occurs in Patients With Drug-Eluting Stent Restenosis

2015 ◽  
Vol 66 (1) ◽  
pp. 14-22 ◽  
Author(s):  
Seiji Habara ◽  
Kazushige Kadota ◽  
Takenobu Shimada ◽  
Masanobu Ohya ◽  
Hidewo Amano ◽  
...  
Keyword(s):  
Balloon Angioplasty ◽  
Drug Eluting Stent ◽  
Stent Restenosis ◽  
Drug Eluting ◽  
Late Restenosis

The effect of REDV/TiO2 coating coronary stents on in-stent restenosis and re-endothelialization

2016 ◽  
Vol 31 (6) ◽  
pp. 911-922 ◽  
Author(s):  
Xiangshan Xu ◽  
Lijie Wang ◽  
Guofeng Wang ◽  
Yuanzhe Jin
Keyword(s):  
Metal Ion ◽  
316L Stainless Steel ◽  
Ceramic Coating ◽  
Bare Metal Stent ◽  
Drug Eluting Stent ◽  
Bare Metal ◽  
Metal Stent ◽  
Stent Restenosis ◽  
Drug Eluting ◽  
In Stent Restenosis

The coronary artery stent has been widely used in clinic. In-stent restenosis was mainly caused by the excessive proliferation of smooth muscle cell and the inflammation due to the metal ion released from stent scaffold of the drug-eluting stent. Thus, to reduce the in-stent restenosis and promote the vascular endothelialization have become a hot research point in this area. In this paper, a nano-TiO2 ceramic coating was deposited on 316L stainless steel to reduce the metal ion release and to inhibit the inflammation reaction. An endothelia cell selective adhesion peptide Arg-Glu-Asp-Val (REDV) coating was prepared on the ceramic coating by a polydopamine technology to promote the endothelialization. The corrosion test indicated that nano-TiO2 ceramic film could effectively decrease the nickel ion released from 316L stainless steel. REDV/TiO2 coating could promote the endothelial cell adhesion and proliferation, meanwhile REDV/TiO2 coating could also increase the nitric oxide concentration. Bare metal stent, TiO2-coated stent and REDV/TiO2-coated stent were implanted in the iliac arteries of rabbit model. In-stent restenosis and re-endothelialization were evaluated at 28 days post-implantation of the stents. The results showed that REDV/TiO2-coated stents could effectively reduce in-stent restenosis and promote re-endothelialization in comparison with TiO2-coated drug-eluting stent and bare metal stent. These results suggest that REDV/TiO2-coated drug-eluting stent maybe a good choice of the application for coronary artery disease.

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