First-in-Human Evaluation of a Polymer-Free Everolimus-Eluting Stent Using a Titanium Dioxide Film.

BACKGROUND: In patients with coronary artery disease treated with permanent polymer-coated drug-eluting stents (DES), the persistent presence of a less biocompatible polymer might delay arterial healing. Thin strut polymer-free DES have the potential to improve clinical outcomes and reduce the duration of dual antiplatelet therapy (DAPT). The purpose of this first-in-human study was to assess the safety and effectiveness of a novel polymer-free DES in patients with de novo coronary lesions. The TIGERevolutioN® stent (CG Bio Co., Ltd., Seoul, Korea) consists of a cobalt chromium platform with a strut thickness of 70 µm and a surface treated with titanium dioxide onto which everolimus-eluting stent (EES) is applied abluminally (6 µg/mm of stent length) without utilization of a polymer. METHODS: A total of 20 patients were enrolled, with de novo coronary lesions (stable or unstable angina) and > 50% diameter stenosis in a vessel 2.25 to 4.00 mm in diameter and ≤ 40 mm in length for angiographic, optical coherence tomography (OCT), and clinical assessment at 8 months. All patients received DAPT after stent implantation. The primary endpoint was angiographic in-stent late lumen loss (LLL) at 8 months. RESULTS: Twenty patients with 20 lesions were treated with TIGERevolutioN®. At 8 months, in-stent LLL was 0.7 ± 0.4 mm. On OCT, percent area stenosis was 29.2 ± 9.4% and stent strut coverage was complete in all lesions. No adverse cardiovascular event occurred at 8 months. CONCLUSION: The new polymer-free EES was safe and effective with low LLL and excellent strut coverage at 8 months of follow-up. TRIAL REGISTRATION: Trial Registration: Clinical Research Information Service Identifier: KCT0005699.

Preclinical Evaluation of a Novel Polymer-free Everolimus-eluting Stent in a Mid-term Porcine Coronary Restenosis Model.

BACKGROUND: Titanium dioxide films exhibit good biocompatibility and may be effective as drug-binding matrices for drug-eluting stents. We conducted a mid-term evaluation of a novel polymer-free everolimus-eluting stent using nitrogen-doped titanium dioxide film deposition (TIGEREVOLUTION®) in comparison with a commercial durable polymer everolimus-eluting stent (XIENCE Alpine®) in a porcine coronary restenosis model. METHODS: Twenty-eight coronary arteries from 14 mini-pigs were randomly allocated to TIGEREVOLUTION® stent and XIENCE Alpine® stent groups. The stents were implanted in the coronary artery at a 1.1-1.2:1 stent-to-artery ratio. Eleven stented coronary arteries in each group were finally analyzed using coronary angiography, optical coherence tomography, and histopathologic evaluation 6 months after stenting. RESULTS: Quantitative coronary analysis showed no significant differences in the pre-procedural, post-procedural, and 6-month lumen diameters between the groups. In the volumetric analysis of optical coherence tomography at 6 months, no significant differences were observed in stent volume, lumen volume, and percent area stenosis between the groups. There were no significant differences in injury score, inflammation score, or fibrin score between the groups, although the fibrin score was zero in the TIGEREVOLUTION® stent group (0 vs. 0.07 ± 0.11, P = 0.180). CONCLUSION: Preclinical evaluation, including optical coherence tomographic findings 6 months after stenting, demonstrated that the TIGEREVOLUTION® stent exhibited efficacy and safety comparable with the XIENCE Alpine® stent, supporting the need for further clinical studies on the TIGEREVOLUTION® stent.

Efficacy and Safety Evaluation of Tacrolimus-Eluting Stent in a Porcine Coronary Artery Model.

BACKGROUND: A drug-eluting stent (DES) is a highly beneficial medical device used to widen or unblock narrowed blood vessels. However, the drugs released by the implantation of DES may hinder the re-endothelialization process, increasing the risk of late thrombosis. We have developed a tacrolimus-eluting stent (TES) that as acts as a potent antiproliferative and immunosuppressive agent, enhancing endothelial regeneration. In addition, we assessed the safety and efficacy of TES through both in vitro and in vivo tests. METHODS: Tacrolimus and Poly(lactic-co-glycolic acid) (PLGA) were applied to the metal stent using electrospinning equipment. The surface morphology of the stent was examined before and after coating using a scanning electron microscope (SEM) and energy dispersive X-rays (EDX). The drug release test was conducted through high-performance liquid chromatography (HPLC). Cell proliferation and migration assays were performed using smooth muscle cells (SMC). The stent was then inserted into the porcine coronary artery and monitored for a duration of 4 weeks. RESULTS: SEM analysis confirmed that the coating surface was uniform. Furthermore, EDX analysis showed that the surface was coated with both polymer and drug components. The HPCL analysis of TCL at a wavelength of 215 nm revealed that the drug was continuously released over a period of 4 weeks. Smooth muscle cell migration was significantly decreased in the tacrolimus group (54.1% ± 11.90%) compared to the non-treated group (90.1% ± 4.86%). In animal experiments, the stenosis rate was significantly reduced in the TES group (29.6% ± 7.93%) compared to the bare metal stent group (41.3% ± 10.18%). Additionally, the fibrin score was found to be lower in the TES group compared to the group treated with a sirolimus-eluting stent (SES). CONCLUSION: Similar to SES, TES reduces neointimal proliferation in a porcine coronary artery model, specifically decreasing the fibrins score. Therefore, tacrolimus could be considered a promising drug for reducing restenosis and thrombosis.

Successful implantation of a novel polymer-free everolimus-eluting stent using nitrogen-doped titanium dioxide film with good patency on follow-up angiography: A case report.

RATIONALE: Despite technological advances in interventional cardiology during the last decades, many concerns remain regarding the narrowing and occlusion of the in-stent area. Particularly, polymer materials pose several problems, including chronic arterial inflammation, impaired arterial healing, and stent thrombosis. To avoid these complications, we invented the TIGEREVOLUTION stent with a cobalt-chromium alloy-based stent platform deposited with N-TiO2 film, which has demonstrated good biocompatibility. As this stent is not coated with polymer, it is expected to have decreased risk of stent thrombosis. PATIENT CONCERNS: A 62-year-old Korean man visited our department because of angina. We commenced coronary angiography (CAG). DIAGNOSIS: CAG revealed critical stenosis in the mid-portion of the right coronary artery, with a minimum lumen area of 1.08mm2 on optical coherence tomography (OCT). INTERVENTION: Percutaneous coronary intervention was performed with implantation of a novel 3.5 × 26-mm polymer-free everolimus-eluting stent using nitrogen-doped titanium dioxide film (TIGEREVOLUTION® stent). Post-percutaneous coronary intervention OCT showed good stent expansion and apposition, and the patient was discharged successfully and uneventfully. OUTCOMES: Eight months later, follow-up coronary angiography demonstrated good stent patency with no definitive evidence of in-stent restenosis, with thin stent strut coverage demonstrated on OCT. LESSONS: We report the first case of TIGEREVOLUTION stent implantation with follow-up OCT at 8 months.

A novel polymer-free drug-eluting stent coated with everolimus using nitrogen-doped titanium dioxide film deposition in a porcine coronary restenosis model.

BACKGROUND: Titanium dioxide (TiO2) films have superior biocompatibility and may be effective as drug-binding matrices for drug-eluting stents (DESs). We sought to evaluate efficacy of a polymer-free DES coated with everolimus using nitrogen-doped TiO2 film deposition in a porcine coronary restenosis model. METHODS: Forty coronary arteries in 20 pigs were randomly allocated to group 1 (bare-metal stents (BMSs), 3.0×18mm, n=10), group 2 (BMSs with nitrogen-doped TiO2 film deposition, 3.0×18mm, n=10), group 3 [commercial everolimus-eluting stent, 3.0×18mm, n=10], and group 4 (polymer-free everolimus-eluting stent using nitrogen-doped TiO2 film deposition, 3.0×18mm, n=10). Stents were randomly implanted in the left anterior descending coronary artery and left circumflex artery with stent:artery ratio of 1.3. Four weeks later, pigs underwent follow-up coronary angiography and were sacrificed for histopathologic analysis. RESULTS: Percent area stenosis was greater in group 1 compared to groups 3 and 4 (46.4±13.8% vs. 30.2±11.7% vs. 29.2±8.9%, respectively, p=0.005). Fibrin score was lower in groups 1 and 2, compared to groups 3 and 4: 0.87±0.67 vs. 0.76±0.61 vs. 2.27±0.24 vs. 1.75±0.31, respectively, p<0.001). Injury score and inflammation score were not different. Comparison between DES showed a higher fibrin score in group 3 than group 4 (2.27±0.24 vs. 1.75±0.31, p=0.023). CONCLUSIONS: In a porcine model of coronary restenosis, a novel polymer-free DES using nitrogen-doped TiO2 film deposition shows higher biocompatibility and compares favorably with a commercial DES.