materials Review Cardiovascular Stents: A Review of Past, Current, and Emerging Devices 1,2 3 4,5, Alexandru Scafa Udris, te , Adelina-Gabriela Niculescu , Alexandru Mihai Grumezescu * and Elisabeta Bădilă 1,6 1 Carol Davila University of Medicine and Pharmacy, 050474 Bucharest, Romania; [email protected] (A.S.U.); [email protected] (E.B.) 2 Cardiology Department, Clinical Emergency Hospital Bucharest, 014461 Bucharest, Romania 3 Faculty of Engineering in Foreign Languages, University Politehnica of Bucharest, 060042 Bucharest, Romania; [email protected] 4 Faculty of Applied Chemistry and Materials Science, University Politehnica of Bucharest, 060042 Bucharest, Romania 5 Research Institute of the University of Bucharest—ICUB, University of Bucharest, 050657 Bucharest, Romania 6 Internal Medicine Department, Clinical Emergency Hospital Bucharest, 014461 Bucharest, Romania * Correspondence: [email protected]; Tel.: +40-21-402-3997 Abstract: One of the leading causes of morbidity and mortality worldwide is coronary artery disease, a condition characterized by the narrowing of the artery due to plaque deposits. The standard of care for treating this disease is the introduction of a stent at the lesion site. This life-saving tubular Citation: Scafa Udris, te, A.; Niculescu, A.-G.; Grumezescu, A.M.; device ensures vessel support, keeping the blood-flow path open so that the cardiac muscle receives B˘adil˘a,E. Cardiovascular Stents: A its vital nutrients and oxygen supply. Several generations of stents have been iteratively developed Review of Past, Current, and towards improving patient outcomes and diminishing adverse side effects following the implanting Emerging Devices. Materials 2021, 14, procedure. Moving from bare-metal stents to drug-eluting stents, and recently reaching bioresorbable 2498. https://doi.org/10.3390/ stents, this research field is under continuous development. To keep up with how stent technology ma14102498 has advanced in the past few decades, this paper reviews the evolution of these devices, focusing on how they can be further optimized towards creating an ideal vascular scaffold. Academic Editors: Rafael Antonio Balart Gimeno, Teodomiro Keywords: cardiovascular stents; stent platform materials; stent optimization; surface functionalization Boronat Vitoria, Joaquim Ciurana Gay, Arantxa Eceiza Mendiguren and Luís Jesús Quiles Carrillo 1. Introduction Received: 7 April 2021 Cardiovascular diseases have become an increasingly serious threat to human life; they Accepted: 10 May 2021 are the leading cause of hospitalization and death globally [1–5]. Coronary artery disease Published: 12 May 2021 (CAD), in particular, is the third most common cause of mortality worldwide, imposing a major health and economic burden on most developed nations [6–11]. CAD is characterized Publisher’s Note: MDPI stays neutral by the narrowing of the artery due to plaque deposits beneath the endothelium. Cells, fats, with regard to jurisdictional claims in calcium, cellular debris, and other substances may accumulate in these deposits, starting published maps and institutional affil- a cascade of events—diminished blood vessel artery lumen, restricted blood flow, and iations. inadequate nutrients and oxygen supply to the cardiac muscle—that can eventually cause myocardial infarction or transient cerebral ischemic attacks and stroke [12–17]. To restore normal blood flow and avoid the other critical consequences of vessel narrowing, special devices called stents can be inserted into the affected vessel using Copyright: © 2021 by the authors. fluoroscopic and/or endoscopic guidance [13,14]. This procedure is minimally invasive Licensee MDPI, Basel, Switzerland. compared to open cardiac surgery and is associated with lower mortality and morbidity in This article is an open access article the long term and better outcomes in critically ill patients in the short term [15]. distributed under the terms and Therefore, cardiovascular stents are life-saving devices, rightfully included in the top conditions of the Creative Commons ten medical breakthroughs of our century [18]. From a constructive point of view, stents Attribution (CC BY) license (https:// are small, complex, cylindrically shaped hollow structures formed into a sequential ring creativecommons.org/licenses/by/ construction comprising a series of struts and connecting elements [13,15,19]. The way that 4.0/). Materials 2021, 14, 2498. https://doi.org/10.3390/ma14102498 https://www.mdpi.com/journal/materials Materials 2021, 14, x FOR PEER REVIEW 2 of 23 Therefore, cardiovascular stents are life-saving devices, rightfully included in the top ten medical breakthroughs of our century [18]. From a constructive point of view, stents Materials 2021, 14, 2498 2 of 22 are small, complex, cylindrically shaped hollow structures formed into a sequential ring construction comprising a series of struts and connecting elements [13,15,19]. The way that stents work relies on their design, which helps keep the path of human arteries stentsthrough work the reliesbody open on their [20,21]. design, which helps keep the path of human arteries through the bodyInitially, open bare-metal [20,21]. stents were used as a bail-out intervention scenario in the case of abruptInitially, and threatened bare-metal vessel stents closure were used with as pl aain bail-out old balloon intervention angioplasty. scenario However, in the case the ofreported abrupt positive and threatened outcomes vessel encouraged closure withstent plain placement old balloon to be adopted angioplasty. as the However, standard the of reportedcare in percutaneous positive outcomes coronary encouraged intervention stent (PCI) placement [22]. Regardless to be adopted of the as history the standard of clinical of caresafety in and percutaneous efficacy, the coronary usage of intervention the first gene (PCI)ration [22 of]. these Regardless devices of was the frequently history of clinicallimited safetyby in-stent and efficacy,restenosis, the resulting usage of thein the first failure generation of the ofexisting these devicesstent or wasa reintervention frequently limited using byanother in-stent stent restenosis, [20]. resulting in the failure of the existing stent or a reintervention using anotherYears stent later, [20 as]. a solution to these issues, the deployment of drug-eluting stents (DESs) becameYears an later, integral as a solutiontreatment to theseoption issues, for patients the deployment with coronary of drug-eluting artery stentsdisease (DESs) [23]. becameCoronary an DESs integral not treatmentonly revolutionized option for PCI patients treatment with coronarybut have also artery been disease approved [23]. Coro-as the narycurrent DESs standard not only as they revolutionized significantly PCI reduce treatment restenosis but of have vascular also beenstents approved and mitigate as thethe currentneed for standard repeat revascularizations as they significantly [20,24,25]. reduce restenosis of vascular stents and mitigate the needThe for repeatdecades revascularizations of research and clinical [20,24,25 trials]. in this field have resulted in various stent designsThe involving decades of diverse research materials, and clinical from trials which in this doctors field have can resultedchoose the in various appropriate stent designsdevice depending involving diverseon the local materials, deposition from whichof plaque doctors and canfatty choose substances the appropriate and the potential device dependingside effects on[15,18]. the local deposition of plaque and fatty substances and the potential side effectsThis [15 ,paper18]. thus aims to review past and currently available stents and shed some light Thison how paper these thus devices aims tocan review be further past optimized and currently towards available ideal stentsin vivo and behavior. shed some light on how these devices can be further optimized towards ideal in vivo behavior. 2. Evolution of Cardiovascular Stents 2. Evolution of Cardiovascular Stents The rapid technological advancements that have taken place over the past 40 years The rapid technological advancements that have taken place over the past 40 years have greatlygreatly affectedaffected PCIPCI evolutionevolution [26[26].]. InterventionalInterventional cardiologycardiology hashas undoubtedlyundoubtedly evolved since thethe firstfirst percutaneouspercutaneous transluminaltransluminal coronarycoronary angioplasty.angioplasty. ThisThis evolutionevolution began with a balloonballoon cathetercatheter mounted on a fixedfixed wirewire andand progressedprogressed intointo bare-metalbare-metal stents (BMSs),(BMSs), first-generationfirst-generation DESs,DESs, andand second-second- andand third-generationthird-generation biodegradablebiodegradable polymer-basedpolymer-based DESs,DESs, culminatingculminating inin thethe introductionintroduction ofof bioresorbablebioresorbable vascularvascular scaffoldsscaffolds (BVSs),(BVSs), whichwhich areare currentlycurrently underunder developmentdevelopment [[7,17]7,17] (Figure(Figure1 ).1). FigureFigure 1. 1. CardiovascularCardiovascular stents stents evolution—a evolution—a brief brief timeline. timeline. Create Createdd based based on oninformation information from from the theliterature literature [7,27–29]. [7,27–29 ]. Stents s were found to have versatile medical applications (Figure(Figure2 2)) in in a a wide wide variety variety of clinical emergencies after after their their introduction introduction by by Charles Charles Theodore Theodore Dotter