A new age of personalized medicine has been ushered in by the development of 3D printing technology, which has emerged in recent years as a revolutionary force in medicine.1 Stent development and application is an area where 3D printing has shown exceptional promise. In interventional cardiology and vascular surgery, stents have long been a standard tool.2,3 Conventional stent manufacturing methods, on the other hand, frequently result in homogenous, mass-produced devices that might not completely address the distinct anatomical variances and physiological requirements of individual patients.4,5 The development of 3D printing technology has created amazing opportunities to produce stents.2,6,7 Complex stent designs may now be modified to fit the unique vascular anatomy of each patient by utilizing medical imaging data, creating a highly customized method that maximizes treatment effectiveness while minimizing side effects.8 This revolutionary transition from "one-size-fits-all" stents to patient-specific implants has the potential to completely modify the way stents are used and enhance patient care. Due to 3D printing's flexibility9 new biomaterials and medication delivery methods may be explored. It is now possible to create temporary stents that naturally dissolve over time, preventing the long-term presence of foreign objects in the body.10 This is made possible using biocompatible and bioresorbable materials in stent manufacture.11,12 Stents made by 3D printing could precisely distribute therapeutic agents to specific locations, improving treatment results and reducing restenosis, a major consequence of stent-based therapies.13 Despite these encouraging developments, incorporating 3D printed stents into widespread clinical use presents a number of unique difficulties.6 For this technology to be used safely and widely, it is imperative that regulatory clearances, standardization, long-term biocompatibility, and cost-effectiveness be carefully considered.14 In this review article, we seek to present a broad overview of recent developments and advances in 3D printing technology and its transformative role in the use of stents, as well as to examine the most innovative materials, design approaches, and preclinical and clinical studies that highlight the potential advantages of 3D printed stents. To fully utilize the potential of 3D printing to better stent treatments and eventually improve patient outcomes, we will examine the regulatory environment and ethical issues. We will also critically assess the obstacles and possibilities that lie ahead. This paper aims to advance existing knowledge of the uses of 3D printing in stent installation and encourage more study and collaboration in this attractive field of 3D printing and medical technology, which is continuing to advance quickly.

The background and history of 3D printing technology in the field of cardio health medical involves the evolution of additive manufacturing techniques and their application to healthcare.15 3D printing, also known as additive manufacturing,16,17 is a method that constructs objects layer by layer, offering high precision and suitability for intricate or personalized items.18 This technology accelerates prototype production, aiding in product evaluation and testing prior to finalization. The term "additive manufacturing" is synonymous with 3D printing and is part of a set of technologies encompassing rapid prototyping and solid freeform fabrication.19,20 These methods employ lasers or advanced printing techniques to incrementally build objects layer by layer. Although 3D printing is gaining attention recently, its principles, software, and tools have a longer history. The origins of 3D printing-related concepts and technologies can be traced back at least 40 years based on records from the United States Patent Office.21,22 Methods tied to 3D printing, such as those used in topographic and photo sculpture, extend even further, spanning about 100 years.23,24 In 1981, a groundbreaking development at the University of Texas at Austin's Cockrell School of Engineering laid the foundation for modern 3D printing technology.25 This process, known as Selective Laser Sintering (SLS), utilized computer-controlled lasers to fuse powdered particles together in layers.26,27 While SLS was an early approach to 3D printing, various patented methods have since emerged as common techniques within the field.28,29 These diverse processes continue to drive advancements in the realm of 3D printing. The distinct 3D models generated by different printing methods offer unique attributes that cater to various industries and purposes. In the context of cardio health medical applications, 3D printing's capacity for precision and customization has led to significant advancements.30 Technology enables the creation of patient-specific models, aiding surgeons in planning complex procedures and enhancing their understanding of individual patient anatomies,31,32 given in Table 1. This capability has revolutionized preoperative planning and training, ultimately improving surgical outcomes and patient care in the field of cardio health medical.33 Traditional manufacturing methods like injection molding and machining come with high costs, extended lead times, and limited design flexibility.34,35 In contrast, 3D printing offers a cost-effective, agile approach, producing intricate shapes with less waste. The medical field swiftly embraced 3D printing's potential, notably for improving patient care.36,37 Custom-designed stents, traditionally restricted by standard sizes, are now crafted using patient-specific data from 3D printing, ensuring precise fits and better outcomes.38 Surgical planning benefits from 3D-printed anatomical models, enhances precision and reduces operating time. Surgical guides aid implant placement, notably in stent procedures. 3D printing revolutionized prosthetics and orthotics, making tailor-made, cost-effective, comfortable devices that restore mobility.39 In regenerative medicine, 3D-printing offers potential for living tissues and organs, serving as models for drug testing and personalized medicine.40 Controlled drug delivery systems emerged via 3D printing, achieving personalized drug release profiles for better efficacy and compliance.41 The process of 3D printing commences with the creation of a three-dimensional model utilizing computer-aided design (CAD) software, subsequently translating it into a physical object through a 3D printer.42,43 To facilitate the construction of objects, specialized programming software is required for 3D printing machines. CAD software, integral to the 3D printing process, involves intricate 3D modeling that necessitates training due to its sophisticated nature.44 CAD software analyzes numerous cross-sections of each product, precisely dictating the construction of each layer.45 The resulting 3D design representation on a two-dimensional screen is then utilized by 3D printers to create physical objects.46,47 Presently, diverse 3D modeling software options are available, with some being open-source and offering training modules.48 3D printing utilizes data from medical scans such as Computed Tomography (CT) and Magnetic Resonance Imaging (MRI) to craft models. Renowned CAD software includes Autodesk, boasting platforms like AutoCAD and Revit, Geomagic Design from 3D Systems, SketchUp which provides free and commercial licenses, and Tinkercad - browser-based software owned by Autodesk.49 These software options generate file formats compatible with 3D printing, often utilizing the STL format native to 3D Systems' stereolithography CAD software. While CAD software is pivotal for original model design, 3D printer-compatible files can also be procured through scanning or downloading. 3D scans from MRI and CT are convertible to printable files.50 Optical scanning technology, found in devices like the Sense scanner or mobile attachments like iSense, captures precise measurements to create an accurate scan in a printable format.51,52 A range of 3D scanners is available in the market, facilitating the acquisition of scan-based 3D printer files.53

Stents are crucial medical implants designed as tubular scaffolds to uphold weakened or constricted blood vessels, bolster blood flow, offer structural support, and prevent vascular collapse.59 Composed of biocompatible metallic alloys or polymers, stents play a pivotal role in various medical contexts. Initially, rigid stainless-steel stents emerged, finding application in large-diameter conduits like the oesophagus and bile ducts.60,61 Addressing concerns of arterial recoil and restenosis post-balloon dilation, coronary stents were conceived.62 The stent landscape encompasses bare metal stents (BMS), drug-eluting stents (DES), and bioresorbable vascular scaffolds (BRS). The pursuit of an "ideal" metallic stent entails a delicate equilibrium of attributes, encompassing high flexibility, deliverability, reduced thrombogenicity, substantial radial force, superior fluoroscopic visibility, and unwavering biocompatibility. BMS exhibit rigidity, while DES incorporate intricate designs with anti-proliferative drug-containing polymers.7,63 BRS, a recent innovation, are crafted from materials like poly-L-lactic acid or magnesium, gradually dissolving to eliminate permanent foreign body presence. The evolution of interventional cardiology traces back to Gruentzig's introduction of balloon-expandable stents in 1977.64 These stents redefined percutaneous transluminal coronary angioplasty by preventing post-dilation artery constriction as shown in Fig. 1. DES emerged in the early 2000s to counter restenosis, utilizing drug-eluting polymer coatings to inhibit smooth muscle cell proliferation.65 Nonetheless, DES introduced challenges such as delayed endothelial healing, impacting long-term artery health and stent thrombosis risk.66,67 Stent architecture, characterized by interlinked struts forming lattice-like structures, wields significant influence. Strut design dictates flexibility, radial strength, and conformability, affecting overall performance.68 In DES, the drug-eluting polymer coating holds vital importance, acting as a drug carrier for agents like sirolimus, paclitaxel, or everolimus.69 The choice of drug and polymer markedly influences drug release kinetics and DES effectiveness. Bioresorbable stents represent a leap in technology, aiming to counter long-term foreign body presence.70,71 Crafted from biodegradable polymers like polylactic acid or polyglycolic acid, these stents gradually dissolve, allowing the treated artery to regain its natural state.72 In the intricate tapestry of stent advancements, the pursuit of the optimal stent continues, balancing mechanical properties, drug delivery, and biocompatibility for superior patient outcomes.73 Stent deployment often employs specialized delivery systems, like balloon catheters, where the stent is mounted on a deflated balloon.74 Upon inflation at the target site, the stent expands, pressing against the vessel wall for deployment. This triggers an inflammatory response involving inflammatory cells and smooth muscle cells, initiating the healing process. Proper endothelialization, where endothelial cells cover the stent, is crucial for preventing thrombosis and promoting vessel healing. Restenosis, caused by neointimal tissue overgrowth, remains a challenge in bare-metal stents, leading to recurrent symptoms. Drug-eluting stents mitigate restenosis by inhibiting smooth muscle cell proliferation.75 Late stent thrombosis, a rare but serious complication, arises months or years post-implantation. It results from delayed endothelial healing, excessive neointimal growth, and incomplete stent strut coverage. Vessel remodeling, involving changes in size and shape, shapes the stented segment's long-term behavior, impacting patency and efficacy.75, 76, 77

The first self-expanding coronary stent was implanted separately by Puel and Sigwart in 1986, marking another important turning point in Percutaneous Coronary Intervention (PCI) history.78 The balloon-expandable stent that Palmaz and Schatz created the following year, was the country's first stent to receive FDA approval. The earliest stents were composed of stainless steel and, although having heavy struts and poor flexibility, they outperformed Plain Old Balloon Angioplasty (POBA) with the removal of abrupt occlusion and a lower rate of restenosis, which was validated in two landmark studies published in 1993 (the BENESTENT and the STRESS trials). Their widespread usage was nevertheless hampered by the high prevalence of acute and subacute stent thrombosis, which forced implanters to utilize high dosages of anticoagulant medications and resulted in unacceptable bleeding rates. Dual antiplatelet treatment (DAPT), which combines ticlopidine or clopidogrel with aspirin, was introduced when it was discovered via intravascular ultrasonography that stents needed high pressure for full growth. At mid- and long-term follow-up, in-stent restenosis (ISR), which has been observed in 15 % to 30 % of treated lesions, was still a major risk with these stents.79, 80, 81

Antiproliferative drugs were the natural solution given that neointimal hyperplasia has been identified as the primary predictor of ISR. Stents were developed into effective local drug delivery platforms in addition to serving as permanent vascular scaffolds. Sousa installed the first DES in Brazil in 1999, ushering in the third dramatic paradigm shift in the discipline's history. The two antiproliferative medications first utilised in first-generation DESs were sirolimus and paclitaxel.82 Both were studied in several randomized controlled trials (RCTs) and showed a substantial decrease in ISR, late lumen loss, and rate of target lesion/vessel revascularization when compared to BMS. Both were constructed of stainless steel and had strut thickness more than 130 m. The initial excitement was dampened by Camenzind's publication of a meta-analysis in 2006, which demonstrated an increased risk of death and myocardial infarction (MI) associated with late and very late stent thrombosis (ST), possibly as a result of delayed endothelialization secondary to antiproliferative drug elution and a hypersensitivity reaction to the polymer coating.83 Sirolimus, also known as rapamycin, was initially intended to be an antifungal medication, but due to unanticipated immunosuppressive effects, its early clinical usage was constrained. It works by impeding the passage from the G1 to the S phase of the cell cycle, which prevents the creation of neointima. The "first-in-man" experience with a Sirolimus-eluting stents (SES) in 2001 had encouraging results, which sparked the creation of the commercial Cypher stent. The SES in De Novo Native Coronary Lesions [SIRIUS] trials and the Randomised Study with the Sirolimus-Eluting Bx Velocity Balloon-Expandable Stent in the Treatment of Patients With De Novo Native Coronary Artery Lesions [RAVEL] trial both showed its effectiveness in preventing ISR. These studies showed that cytostatic compound elution from a stent may significantly lower the rate of ISR and raise the rate of target vessel revascularization (TVR) in PCI patients. The therapeutic justifications for SESs' reduction of ISR in unstable and diabetic plaques were further enlarged by other investigations.84, 85, 86

The SES was contemporaneous with the Taxus Express Paclitaxel Eluting Stent (PES).87 Initially licensed for the treatment of ovarian cancer, paclitaxel's strong cytostatic qualities made it ineffective for that condition. A potential DES candidate chemical. Longer stabilization of Paclitaxel during mitosis, microtubules cause cell cycle arrest, resulting in preventing cellular growth and causing SMC inhibition animal research on proliferation and neointimal formation. This study served as inspiration for randomized trials called the "TAXUS trials" 88 including TAXUS V and VI showed long-term effectiveness of PES's in high-risk, real-world patients who have intricate coronary lesions. Very late ST is an uncommon occurrence, yet it is now understood that it might be a first-generation DES problem. Several meta-analyses and data registries have given comfort to the use of such devices.69,89,90

With the switch to metal alloys (cobalt- or platinum-chromium), the platform for second-generation DES was made more flexible and allowed for a reduction in strut thickness.91,92 To create polymers with quicker drug elution and hence earlier endothelium coverage, novel, more biocompatible compounds like zotarolimus, everolimus, and novolimus (drugs from the limus family) were used.13,90 The zotarolimus-eluting stent (ZES) is a second-generation stent with increased flexibility and smaller strut sizes that is built on a cobalt chromium stent platform.93 A unique phosphorylcholine polymer covering a stable, lipid membrane mimic is also used by the ZES to maximise biocompatibility and reduce inflammation brought on by earlier polymers. Additionally, the polymer was designed to speed up drug elution so that minimal medication remains on the stent after the first damage period, enabling natural artery healing to take place. A derivative of sirolimus, zotarolimus has improved lipophilic characteristics in addition to comparable immunosuppressive activities. The main difference served to improve localisation at the vessel wall and reduce dispersion into the circulation. Preliminary animal studies did in fact support the possible advantages. In fact, compared to SESs and PESs, this innovative stenting system showed better re-endothelialization and decreased local inflammation in preclinical animal models, which indicated the prospective advantages of the device. A cell cycle inhibitor is everolimus, a sirolimus derivative.94 Everolimus eluting stents (EES), which was first introduced in 1997, was created to try to circumvent the physicochemical limitations of characteristics that made sirolimus oral administration effective, difficult. Everolimus prevents SMC, proliferation in vitro and prevents the thickening of vascular intima in transplant models in animals. Cytostatic characteristics made it a possibly useful addition to the developing arsenal against ISR, which led to the creation of the Xience-V/Promus CoCr EES in addition to ZES. In 2004, Grube et al. conducted the First Use to Underscore Restenosis Reduction with Everolimus (FUTURE I) trial, which was a prospective, randomized, single-center study. The trial demonstrated that using EES showed both safety and reduced narrowing of the stented area compared to BMS after 12 months. Following this, the SPIRIT FIRST trial evaluated the Xience V Everolimus-Eluting Coronary Stent System and found similar positive outcomes against BMS for treating new coronary lesions. Subsequently, the SPIRIT II trial revealed better results in terms of late lumen loss and neointimal volumes compared to the PES. Likewise, the SPIRIT III trial compared the Xience-V and Taxus Express, showing superior results in terms of late lumen loss and lower Major Adverse Cardiac Events (MACE) rates, primarily due to fewer occurrences of Myocardial Infarctions (MIs). The initial generation of SESs and PESs brought significant advancements to treating obstructive coronary artery disease (CAD) by substantially reducing ISR. The succeeding generation of stents is characterized by their safety, effectiveness, and a slight enhancement in outcomes compared to their first-generation counterparts. This distinction in outcomes was underscored by a recent comprehensive study involving a considerable number of patients (94,384 individuals). When compared to the first-generation DESs and BMSs, the second-generation devices exhibit a lower risk of ISR, Stent Thrombosis (ST), and mortality. As a result, these newly developed stent platforms stand as the pinnacle of DES design, forming the fundamental basis of contemporary PCI. Second-generation devices are presently the most common coronary stents inserted globally in modern practice.95 They have demonstrated significantly lower rates of MI, target lesion revascularization, and ST as compared to first-generation DES in various RCTs that evaluated its safety and effectiveness.7,96 With these fundamental advancements, second-generation DESs have completely replaced BMS and first-generation DES to become the most popular DES in the world and the preferred percutaneous therapy for CAD. There are still worries regarding their long-term safety, despite the significant technical advancements. The frequency of late and very late ST dropped with a rate of less than 1 % at 5 years, which is lower than that of BMS but still causes worry because DAPT must be continued for at least a year afterward. The development of third-generation devices has also been motivated by the prevalence of late events and efforts to reduce the length and severity of the dual antiplatelet regimen.97, 98, 99

By inducing a possible chronic inflammatory stimulation that results in delayed endothelial coverage and ST, the polymer coat plays a role in the aetiology of long-term stent failure. The development of polymer-free DES, which can theoretically prevent these long-term deleterious effects, decreases the pace of ST, and permits a shorter time of DAPT, has therefore been a novel way to remove polymer-mediated problems.100 The creation of polymer-free DES, however, necessitated the development of new technologies to maintain an acceptable level of antiproliferative medication over time without the polymer vehicle since the polymer not only serves as a drug carrier but also controls the controlled release of the drug over time. To date, few RCTs have evaluated the performances of polymer-free DES and larger trials are needed on long-term efficacy and safety. Other third-generation stents appear to achieve the same goal with small biodegradable polymer dots on the abluminal surface of the stent. polymer-free stents remove the risks linked to polymers, but they require new methods to attach drugs to the stent strut surface. These methods include saturating the metal surface, directly chemically bonding the drug, or connecting the drug using non-polymeric biodegradable materials. Despite the promising potential, this approach is still in its early stages, with only short-term data indicating acceptable levels of safety and effectiveness.69,101,102

DES's coated with biodegradable polymers, such as poly-DL-lactide-co-glycolide or PLLA, may function as a BMS later while initially providing the advantages of a regular DES. In the initial stages following implantation, the bioresorbable polymer degrades concurrently with the controlled release of the antiproliferative medication. Only the metallic platform is left in the coronary artery once the medication has completely eluted, and the polymer has degraded. There are several bioresorbable polymers in use today, and they vary in terms of biocompatibility, rate of breakdown, and effects on endothelial function, development of smooth muscle cells, and thrombogenicity. Despite theoretical benefits and positive early data, which showed first-generation DESs to have lower rates of extremely late ST and were superior in terms of effectiveness and safety.103,104

Interest in fully Bioresorbable Stents (BRS)has surged in the last decade due to concerns about long-term effects from persistent metallic structures in coronary arteries, potentially heralding a new era in interventional cardiology. The aim is to prevent immediate restenosis and vascular recoil while providing temporary mechanical support in the artery. Over time, the metallic scaffold dissolves, eliminating the potential for lasting harm. These devices, also known as BRSs, initially provide mechanical support and localized drug delivery similar to permanent metallic DESs for the first year before completely resorbing in 2 to 3 years. This gradual process restores normal luminal size and function, reduces the risk of late adverse events, potentially decreases the need for long-term DAPT, and allows for surgical revascularization if needed. Bioresorbable Vascular Scaffolds (BVS) can be made from a polymer coated with antiproliferative drugs or a metallic alloy (such as magnesium or iron alloy). The first drug-eluting bioresorbable stent was implanted in 1995, and since then, about 9 different types have been studied in clinical trials. However, only a few of them have received regulatory approvals. The most well-known one, the Absorb BVS from Abbott, was later withdrawn from the market due to increased rates of stent thrombosis. Metallic BRS's are becoming more popular because they address the weaknesses of biodegradable polymer stents by offering stronger radial support and thinner struts.105 The main challenge faced by BRS, particularly those made of first-generation PLLA, is dealing with recoil and limited radial force due to quick absorption. This requires stent designs with thicker struts, which can lead to incomplete expansion and smaller luminal diameter after deployment. Metallic BRS's are gaining favor due to their ability to address these issues. Recent studies have shown higher rates of device thrombosis and myocardial infarction with current-generation PLLA-BRS, particularly the Absorb BVS, leading to restrictions on its use for controlled studies or registries. The emergence of fully bioresorbable stents presents a potential breakthrough in interventional cardiology. While they offer benefits like reduced long-term risks, challenges related to stent structure and performance, especially in the context of current-generation bioresorbable stents, need further investigation and refinement.106,107