Structural and temporal dynamics analysis of zinc-based biomaterials: History, research hotspots and emerging trends.

Objectives: To examine the 16-year developmental history, research hotspots, and emerging trends of zinc-based biodegradable metallic materials from the perspective of structural and temporal dynamics. Methods: The literature on zinc-based biodegradable metallic materials in WoSCC was searched. Historical characteristics, the evolution of active topics and development trends in the field of zinc-based biodegradable metallic materials were analyzed using the bibliometric tools CiteSpace and HistCite. Results: Over the past 16 years, the field of zinc-based biodegradable metal materials has remained in a hotspot stage, with extensive scientific collaboration. In addition, there are 45 subject categories and 51 keywords in different research periods, and 80 papers experience citation bursts. Keyword clustering anchored 3 emerging research subfields, namely, #1 plastic deformation #4 additive manufacturing #5 surface modification. The keyword alluvial map shows that the longest-lasting research concepts in the field are mechanical property, microstructure, corrosion behavior, etc., and emerging keywords are additive manufacturing, surface modification, dynamic recrystallization, etc. The most recent research on reference clustering has six subfields. Namely, #0 microstructure, #2 sem, #3 additive manufacturing, #4 laser powder bed fusion, #5 implant, and #7 Zn-1Mg. Conclusion: The results of the bibliometric study provide the current status and trends of research on zinc-based biodegradable metallic materials, which can help researchers identify hot spots and explore new research directions in the field.

Herbal medicine formula Huazhuo Tiaozhi granule ameliorates dyslipidaemia via regulating histone lactylation and miR-155-5p biogenesis.

BACKGROUND: Huazhuo Tiaozhi granule (HTG) is a herbal medicine formula widely used in clinical practice for hypolipidaemic effects. However, the molecular mechanisms underlying dyslipidaemia treatment have not been well elucidated. RESULTS: A significant reduction in the levels of total cholesterol (TC) and low-density lipoprotein cholesterol (LDL-C) was observed in the serum of patients with dyslipidaemia after HTG treatment, without disruption in the levels of aspartate transaminase (AST), alanine transaminase (ALT), urea nitrogen (BUN), and creatinine (Cr). The dyslipidaemia rat model was induced by a high-fat diet and treated with Xuezhikang (0.14 g/kg/d) or HTG (9.33 g crude herb/kg/day) by gavage for 8 weeks. Body weight and liver index were markedly decreased in dyslipidaemic rats after treatment with Xuezhikang or HTG. HTG administration markedly ameliorated hyperlipidaemia by decreasing the levels of TC and LDL-C in serum and hepatic lipid accumulation. In vitro, lipid accumulation in LO2 and HepG2 cells was alleviated by serum treatment with HTG. High lactylation was observed in 198 proteins, including lactylation of histone H2B (K6), H4 (K80). Deep sequencing of microRNAs showed that miR-155-5p was significantly downregulated. CONCLUSIONS: This study demonstrates that HTG is an effective and safe formula for treating dyslipidaemia, which promotes lactylation in hepatocytes, and the retardation of miR-155-5p biogenesis.

The Janus-faced role of Piezo1 in cardiovascular health under mechanical stimulation.

In recent years, cardiovascular health problems are becoming more and more serious. At the same time, mechanical stimulation closely relates to cardiovascular health. In this context, Piezo1, which is very sensitive to mechanical stimulation, has attracted our attention. Here, we review the critical significance of Piezo1 in mechanical stimulation of endothelial cells, NO production, lipid metabolism, DNA damage protection, the development of new blood vessels and maturation, narrowing of blood vessels, blood pressure regulation, vascular permeability, insulin sensitivity, and maintenance of red blood cell function. Besides, Piezo1 may participate in the occurrence and development of atherosclerosis, diabetes, hypertension, and other cardiovascular diseases. It is worth noting that Piezo1 has dual effects on maintaining cardiovascular health. On the one hand, the function of Piezo1 is necessary to maintain cardiovascular health; on the other hand, under some extreme mechanical stimulation, the overexpression of Piezo1 may bring adverse factors such as inflammation. Therefore, this review discusses the Janus-faced role of Piezo1 in maintaining cardiovascular health and puts forward new ideas to provide references for gene therapy or nanoagents targeting Piezo1.

Senescent endothelial cells' response to the degradation of bioresorbable scaffold induces intimal dysfunction accelerating in-stent restenosis.

Atherosclerotic cardiovascular disease is a typical age-related disease accompanied by stiffening arteries. We aimed to elucidate the influence of aged arteries on in-stent restenosis (ISR) after the implantation of bioresorbable scaffolds (BRS). Histology and optical coherence tomography showed increased lumen loss and ISR in the aged abdominal aorta of Sprague-Dawley rats, with apparent scaffold degradation and deformation, which induce lower wall shear stress (WSS). This was also the case at the distal end of BRS, where the scaffolds degraded faster, and significant lumen loss was followed by a lower WSS. In addition, early thrombosis, inflammation, and delayed re-endothelialization were presented in the aged arteries. Degradation of BRS causes more senescent cells in the aged vasculature, increasing endothelial cell dysfunction and the risk of ISR. Thus, profoundly understanding the mechanism between BRS and senescent cells may give a meaningful guide for the age-related scaffold design. STATEMENT OF SIGNIFICANCE: The degradation of bioresorbable scaffolds aggravates senescent endothelial cells and a much lower wall shear stress areas in the aged vasculature, lead to intimal dysfunction and increasing in-stent restenosis risk. Early thrombosis and inflammation, as well as delayed re-endothelialization, are presented in the aged vasculature after bioresorbable scaffolds implantation. Age stratification during the clinical evaluation and senolytics in the design of new bioresorbable scaffolds should be considered, especially for old patients.

Biodegradable polymeric nanoparticles increase risk of cardiovascular diseases by inducing endothelium dysfunction and inflammation.

Biodegradable polymers are expected to be an alternative to plastics. Because of its high biocompatibility, poly (lactic-co-glycolic acid) (PLGA) is widely used in medicine. It has been reported that micro-nano plastics can be accumulated in the circulatory system and cause tissue injury. With the increasing environmental exposure of degradable polymer nanoparticles (NPs), the impact of this risk factor on cardiovascular disease deserves attention. Thus, we aim to study the harmful effect of PLGA NPs on the process of vascular stenosis which is a typical pathological feature of cardiovascular diseases. We establish a mouse vascular stenosis model with intravenously injecting of PLGA NPs for 2 weeks. This model leads to a significant narrowing of the left common carotid artery which is characterized by the increasing intima area and focal stenosis. We observe that PLGA NPs accelerate stenosis progression by inducing inflammation and impairing vascular function. It promotes the proliferation of smooth muscle cells and causes abnormal collagen distribution. The combination of wall shear stress and PLGA NPs uptake speed up endothelial cell damage, decrease endothelial permeability and cell migration capacity. Our results suggest that PLGA NPs may pose a risk in cardiovascular stenosis which inspire us to concern the biodegradable polymeric materials in our living especially the clinic applications.

Facile preparation of a metal-phenolic network-based lymph node targeting nanovaccine for antitumor immunotherapy.

Cancer vaccines are being explored for enhanced cancer immunotherapy and prophylaxis. Some of their prevailing weaknesses, however, such as complicated preparation, poor biocompatibility, and failure to elicit strong cellular immune responses, have limited their further clinical applications. Here, we reported a multifunctional nanovaccine that was prepared in a quick and simple way. During the self-assembly of metal-phenolic networks (MPNs), the antigen ovalbumin (OVA) and immunoreactive chlorogenic acid (CHA) were simultaneously loaded. Owing to its dual pH and reduction sensitivities, the nanovaccine could deliver antigens into the cytoplasm of dendritic cells (DCs) and facilitate the cross-presentation of antigens. Moreover, the results of in vivo immunization assays demonstrated that the nanovaccine significantly excited the antigen presentation of DCs and provoked a robust cellular immune response with the restrained activation of regulatory T cells (Tregs), by targeting lymph nodes and executing the function of CHA. In vivo antitumor assays indicated that the nanovaccine with good biocompatibility afforded conspicuous cancer treatment and prevention effects. Overall, the nanovaccine presented in this study shows a promise for potentiating cancer immunotherapy by the lymph node-targeted delivery. STATEMENT OF SIGNIFICANCE: Cancer nanovaccines can be used for cancer immunotherapy. However, some existing shortcomings, such as cumbersome preparation, poor biocompatibility, and failure to elicit strong immune responses, limit the clinical application of cancer nanovaccines. This study developed a multifunctional nanovaccine that was readily prepared through the self-assembly of metal-phenolic networks. The nanovaccine with dual pH and reduction sensitivities could efficiently promote the antigen lysosome escape and cross-presentation. In vivo, it efficiently delivered antigen into lymph nodes and provoked strong cellular immune responses, and thus it showed significant cancer immunotherapy and prevention effect.

Structural and temporal dynamics analysis on drug-eluting stents: History, research hotspots and emerging trends.

Purpose: This review aims to explore the history, research hotspots, and emerging trends of drug-eluting stents(DES)in the last two decades from the perspective of structural and temporal dynamics. Methods: Publications on DES were retrieved from WoSCC. The bibliometric tools including CiteSpace and HistCite were used to identify the historical features, the evolution of active topics, and emerging trends on the DES field. Results: In the last 20 years, the field of DES is still in the hot phase and there is a wide range of extensive scientific collaborations. In addition, active topics emerge in different periods, as evidenced by a total of 41 disciplines, 511 keywords, and 1377 papers with citation bursts. Keyword clustering anchored five emerging research subfields, namely #0 dual antiplatelet therapy, #3 drug-coated balloon, #4 bifurcation, 5# rotational atherectomy, and 6# quantitative flow ratio. The keyword alluvial map shows that the most persistent research concepts in this field are thrombosis, restenosis, etc., and the emerging keywords are paclitaxel eluting balloon, coated balloon, drug-eluting balloon, etc. There are 7 recent research subfields anchored by reference clustering, namely #2 dual antiplatelet therapy, #4 drug-coated balloon, #5 peripheral artery disease, #8 fractional flow reserve, #10 bioresorbable vascular scaffold, # 13 intravascular ultrasound, #14 biodegradable polymer. Conclusion: The findings based on the bibliometric studies provide the current status and trends in DES research and may help researchers to identify hot topics and explore new research directions in this field.

Global trends and frontiers in research on coronary microvascular dysfunction: a bibliometric analysis from 2002 to 2022.

BACKGROUND: Coronary microvascular dysfunction (CMD) is a leading cause of ischemic heart disease. Over the past few decades, considerable progress has been made with respect to research on CMD. The present study summarized the current research hotspots and trends on CMD by applying a bibliometric approach. METHODS: Relevant publications between 2002 and 2022 were extracted from the Web of Science Core Collection. Visualization network maps of countries, institutions, authors, and co-cited authors were built using VOSviewer. CiteSpace was used for keyword analysis and the construction of a dual-map overlay of journals and a timeline view of co-cited references. RESULTS: 1539 CMD-related publications were extracted for bibliometric analysis. The annual publications generally showed an upward trend. The United States of America was the most prolific country, with 515 publications (33.5%). Camici P. G. was the most influential author, whereas the European Heart Journal, Circulation, and Journal of the American College of Cardiology were the most authoritative journals. Research hotspot analysis revealed that endothelial dysfunction as well as reduced nitric oxide production or bioavailability played critical roles in CMD development. Positron emission tomography was the most widely used imaging method for diagnosis. In addition, microvascular angina, hypertrophic cardiomyopathy, and heart failure have attracted much attention as the main clinical implications. Furthermore, international standards for CMD diagnosis and management may be the future research directions. CONCLUSIONS: This study offers a comprehensive view about the hotspots and development trends of CMD, which can assist subsequent researchers and guide future directions.

The endothelium permeability after bioresorbable scaffolds implantation caused by the heterogeneous expression of tight junction proteins.

As one of the main functions of vascular endothelial cells, Vascular permeability is determined by four tight junction proteins (TJPs): Zonula Occludens-1 (ZO-1), Claudin-5, Occludin and Tricellulin. The barrier function of blood vessels will be reconstructed after they are damaged by endothelial mechanical injuries caused by vascular interventions. In this study, the effects of balloon expansion (transient mechanical injury) on four TJPs and vascular permeability were compared with those of poly-l-lactic acid bioresorbable scaffolds (BRSs) implantation (continuous mechanical stimulation). We found that BRSs do not affect vascular permeability, while the recovery of vascular barrier function was found to be only related to the mechanical injuries and repair of endothelium. Mechanical stimulation affects and accelerates the recovery process of vascular permeability with the heterogeneous expression levels of TJPs induced after BRSs implantation. Different TJPs have different sensitivity to different loyal mechanical stimuli. ZO-1 is more sensitive to shear stress and tension than to static pressure. Occludin is sensitive to static pressure and shear stress. Tricellulin is more sensitive to tension stretching. Compared with the other three TJPs, Claudin-5 can respond to mechanical stimulation, with relatively low sensitivity, though. This difference in sensitivity determines the heterogeneous expression of TJPs. Mechanical stimulation of different kinds and strengths can also cause different cell morphological changes and inflammatory reactions. As an important element affecting endothelial function, the mechanical factors emerging after BRSs implantation are worthy of more attention.

Crosstalk between arterial components and bioresorbable, 3-D printed poly-L-lactic acid scaffolds.

Bioresorbable scaffolds (BRSs) are designed to provide a temporary support that subsequently leaves behind native vessels after its complete degradation. The accumulation of mechanical changes influences the vascular histological characteristics and vice versa, leading to crosstalk and various behaviors in BRSs in different arterial components, which is different from that observed in traditional metal stents. Hence, we analyzed typical elastic and muscular arteries, the abdominal aorta of Sprague-Dawley rats and carotid arteries of New Zealand rabbits, after both received 3-D printed poly-L-lactic acid BRSs. We observed a lower level of scaffold degradation and severe intimal hyperplasia in the carotid arteries of rabbits because of the synthetic phenotypic transformation of vascular smooth muscle cells (SMCs) and endothelial-to-mesenchymal transition of endothelial cells (ECs). Extracellular matrix remodeling and endothelial repair occurred in a less rapid manner in the abdominal aorta of rats. These results suggest that muscular arterial components such as SMCs and ECs are more sensitive to BRS degradation-induced mechanical changes compared to those of elastic arteries. Therefore, the rat abdominal aorta might be more suitable for assessing BRS degradation and safety, while the carotid artery of rabbits could be used to evaluate drug coatings on BRSs, as it closely reflects the recovery of ECs and proliferation of SMCs. Our study also confirmed that the histological characteristics of vasculature should be considered while choosing an animal model for BRS evaluation.

Global Research Trends on Ventricular Remodeling: A Bibliometric Analysis From 2012 to 2022.

Ventricular remodeling is the progressive pathologic change of the original substance and morphology of the ventricle caused by various injuries and has attracted increasing attention in the past decade. This study aims to conduct a bibliometric analysis of articles on ventricular remodeling published in the Web of Science Core Collection database from 2012 to 2022 to understand the current research state in the field of ventricular remodeling and provide insights for clinicians and researchers. As a result, a total of 1710 articles on ventricular remodeling were included. Annual publications have been gradually increasing and have remained at a high level over the past 10 years. The United States of America contributed the most publications, followed by China. Circulation was the most mainstream and authoritative journal focusing on ventricular remodeling. Research hotspot analysis suggested that myocardial infarction was the primary risk factor for ventricular remodeling, and emerging risk factor studies have focused on pulmonary hypertension, aortic stenosis, and diabetes. The mechanisms in the pathogenesis of ventricular remodeling were mainly closely associated with inflammation, apoptosis, oxidative stress, and myocardial fibrosis. Intensive investigation of the interactions between different mechanisms might be a future research direction. In terms of treatment, cardiac resynchronization therapy was a hot topic of research. These findings can help researchers grasp the research status of ventricular remodeling and determine future research directions.

Two-stage degradation and novel functional endothelium characteristics of a 3-D printed bioresorbable scaffold.

Bioresorbable scaffolds have emerged as a new generation of vascular implants for the treatment of atherosclerosis, and designed to provide a temporary scaffold that is subsequently absorbed by blood vessels over time. Presently, there is insufficient data on the biological and mechanical responses of blood vessels accompanied by bioresorbable scaffolds (BRS) degradation. Therefore, it is necessary to investigate the inflexion point of degradation, the response of blood vessels, and the pathophysiological process of vascular, as results of such studies will be of great value for the design of next generation of BRS. In this study, abdominal aortas of SD rats were received 3-D printed poly-l-actide vascular scaffolds (PLS) for various durations up to 12 months. The response of PLS implanted aorta went through two distinct processes: (1) the neointima with desirable barrier function was obtained in 1 month, accompanied with slow degradation, inflammation, and intimal hyperplasia; (2) significant degradation occurred from 6 months, accompanied with decreasing inflammation and intimal hyperplasia, while the extracellular matrix recovered to normal vessels which indicate the positive remodeling. These in vivo results indicate that 6 months is a key turning point. This "two-stage degradation and vascular characteristics" is proposed to elucidate the long-term effects of PLS on vascular repair and demonstrated the potential of PLS in promoting endothelium function and positive remodeling, which highlights the benefits of PLS and shed some light in the future researches, such as drug combination coatings design.

Phagocytosis of polymeric nanoparticles aided activation of macrophages to increase atherosclerotic plaques in ApoE-/- mice.

The unique physiochemical properties of nanomaterials have been widely used in drug delivery systems and diagnostic contrast agents. The safety issues of biomaterials with exceptional biocompatibility and hemo-compatibility have also received extensive attention at the nanoscale, especially in cardiovascular disease. Therefore, we conducted a study of the effects of poly (lactic-co-glycolic acid) nanoparticles (PLGA NPs) on the development of aortic atherosclerotic plaques in ApoE-/- mice. The particle size of PLGA NPs was 92.69 ± 3.1 nm and the zeta potential were - 31.6 ± 2.8 mV, with good blood compatibility. ApoE-/- mice were continuously injected with PLGA NPs intravenously for 4 and 12 weeks. Examination of oil red O stained aortic sinuses confirmed that the accumulation of PLGA NPs caused a significantly higher extension of atherosclerotic plaques and increasing the expression of associated inflammatory factors, such as TNF-α and IL-6. The combined exposure of ox-LDL and PLGA NPs accelerated the conversion of macrophages to foam cells. Our results highlight further understanding the interaction between PLGA NPs and the atherosclerotic plaques, which we should consider in future nanomaterial design and pay more attention to the process of using nano-medicines on cardiovascular diseases.

Penetration of the blood-brain barrier and the anti-tumour effect of a novel PLGA-lysoGM1/DOX micelle drug delivery system.

Effective treatment of glioma and other central nervous system (CNS) diseases is hindered by the presence of the blood-brain barrier (BBB). A novel nano-delivery vehicle system composed of PLGA-lysoGM1/DOX micelles was developed to cross the BBB for CNS treatment. We have shown that doxorubicin (DOX) as a model drug encapsulated in PLGA-lysoGM1 micelles can achieve up to 3.8% loading efficiency and 61.6% encapsulation efficiency by the orthogonal test design. Our in vitro experiments demonstrated that PLGA-lysoGM1/DOX micelles had a slow and sustainable drug release under physiological conditions and exhibited a high cellular uptake through the macropinocytosis and the autophagy/lysosomal pathways. In vivo experimental studies in zebrafish and mice confirmed that PLGA-lysoGM1/DOX micelles could cross the BBB and be specifically accumulated in the brain. Moreover, an excellent anti-glioma effect was observed in intracranial glioma-bearing rats. Therefore, PLGA-lysoGM1/DOX micelles not only effectively can cross the BBB, but our results also suggest that they have great potential for anti-glioma therapy and other central nervous system diseases.

Inhibition of in-stent restenosis after graphene oxide double-layer drug coating with good biocompatibility.

In this study, we designed a double layer-coated vascular stent of 316L stainless steel using an ultrasonic spray system to achieve both antiproliferation and antithrombosis. The coating included an inner layer of graphene oxide (GO) loaded with docetaxel (DTX) and an outer layer of carboxymethyl chitosan (CMC) loaded with heparin (Hep). The coated surface was uniform without aggregation and shedding phenomena before and after stent expanded. The coating treatment was able to inhibit the adhesion and activation of platelets and the proliferation and migration of smooth muscle cells, indicating the excellent biocompatibility and antiproliferation ability. The toxicity tests showed that the GO/DTX and CMC/Hep coating did not cause deformity and organ abnormalities in zebrafish under stereomicroscope. The stents with GO double-layer coating were safe and could effectively prevent thrombosis and in-stent restenosis after the implantation into rabbit carotid arteries for 4-12 weeks.

An asymmetrical dual coating on the stent prepared by ultrasonic atomization.

This study aims to design an asymmetric dual coating (ADC) on the stent by ultrasonic atomization to solve the problem of delayed endothelialization and late or very late stent thrombosis which caused by drug eluting stent (DES) with symmetric coating. Chitosan-loaded monoclonal platelet glycoprotein IIIa receptor antibody SZ-21 coating (CSC) was sprayed on inner surface of stents, and outer surface was sprayed CSC and poly(lactic-co-glycolic acid) (PLGA) loaded with docetaxel (DTX) coating (PDC). The coated surface was uniform without aggregation and no shedding phenomenon either before or after stent expanded. Fluorescence labeling has confirmed that the coating has an asymmetric structure. The cumulative release for SZ-21 and DTX was 40.11% and 27.22% within first 24 h, then DTX became the major released drug from 24 h to 7 d, after released for 28 d about 40% of the SZ-21 and 50% DTX still remained on the coated stent. It achieved that ADC can inhibit thrombosis at earlier period and inhibit vascular smooth muscle cells (VSMCs) proliferation at later period. And that ADC has good hemocompatibility and can significantly inhibit VSMCs proliferation. Finally, 4 and 12 weeks after the stent with ADC implanted into rabbit carotid arteries, it showed that the stent with ADC was safe and could effectively prevent thrombosis and in-stent restenosis. © 2018 Wiley Periodicals, Inc. J. Biomed. Mater. Res. Part B, 2018. © 2018 Wiley Periodicals, Inc. J Biomed Mater Res Part B: Appl Biomater 107B: 825-837, 2019.

[Endothelial injury and its repair strategies after intravascular stents implantation].

Coronary atherosclerotic heart disease is a serious threat to human life and health. In recent years, the main treatment for it is to implant the intravascular stent into the lesion to support blood vessels and reconstruct blood supply. However, a large number of experimental results showed that mechanical injury and anti-proliferative drugs caused great damage after stent implantation, and increased in-stent restenosis and late thrombosis risk. Thus, maintaining the integrity and normal function of the endothelium can significantly reduce the rate of thrombosis and restenosis. Stem cell mobilization, homing, differentiation and proliferation are the main mechanisms of endothelial repair after vascular stent implantation. Vascular factor and mechanical microenvironmental changes in implanted sites have a certain effect on re-endothelialization. In this paper, the process of injury caused by stent implantation, the repair mechanism after injury and its influencing factors are expounded in detail. And repairing strategies are analyzed and summarized. This review provides a reference for overcoming the in-stent restenosis, endothelialization delay and late thrombosis during the interventional treatment, as well as for designing drug-eluting and biodegradation stents.

Arsenic Trioxide-Coated Stent Is an Endothelium-Friendly Drug Eluting Stent.

An ideal vascular stent would both inhibit in-stent restenosis (ISR) and promote rapid re-endothelialization. In the current study, the performance of arsenic trioxide (ATO)-drug eluting stent (AES) is compared with the bare metal stent, poly-lactic-co-glycolic acid-coating metal stent, and rapamycin-drug eluting stent (RES). In vivo AES is shown to prevent neointimal hyperplasia more efficiently than the others when implanted into the carotid arteries of rabbits. Moreover, AES promotes endothelial cells proliferation and re-endothelialization more quickly than RES. In vitro ATO exposure significantly increases the viability, proliferation, adhesion, and spreading of primary porcine coronary artery endothelial cells (PCAECs), which are critical for endothelialization. However, ATO exposure reduces the viability of porcine coronary artery smooth muscle cells (PCASMCs). The evaluation of mitochondrial morphology, membrane potential, and function demonstrates that ATO at 2 µmol L-1 causes enlargement of the mitochondrion, enhancement of mitochondrial membrane potential, and adenosine triphosphate (ATP) production in PCAECs but not in PCASMCs. Thus, both in vivo and in vitro studies demonstrate that AES is an effective strategy for rapid re-endothelialization and inhibition of ISR.

A "Jail Escape Technique" (JET) for distal side branch wiring during provisional stenting: Feasibility and first-in-man study.

OBJECTIVE: To evaluate the feasibility of a novel technique for achieving distal SB access and improve strut apposition during provisional stenting. BACKGROUND: While distal rewiring and stent expansion toward the side branch (SB) are associated with better results during provisional stenting of coronary artery bifurcation lesions, these techniques are technically challenging and often leave unopposed struts near the carina. METHODS: The "Jail Escape Technique" (JET) is performed by passing the proximal tip of the SB wire between the main vessel (MV) stent struts and balloon before implantation, allowing the MV stent to push the SB wire against the distal part of the carina. The MV stent can then be deployed without jailing the SB wire. Distal SB access and strut distribution at the carina were tested in phantom and swine models. Stent distortion, dislodgement forces, and material damage were evaluated with tensile testing. Human feasibility was then tested on 32 patients. RESULTS: Preclinical testing demonstrated that the SB wire was located at the most distal part of the carina and no strut malapposition at the carina was present after balloon inflation. Stent distortion, dislodgement forces, or material damage were not affected. JET was successfully performed in 30 of 32 patients. No major adverse cardiovascular events occurred in any patient at 6-month follow-up. CONCLUSION: The "JET" enables distal SB access and eliminates strut malapposition at the carina. Further studies with larger numbers of patients are needed to further investigate this technique.