Department of Cardiovascular Surgery, Department of Biotherapy, Cancer Center and State Key Laboratory of Biotherapy, West China Hospital, Sichuan University, Chengdu 610041, China
b.
Clinical Medical College & Affiliated Hospital of Chengdu University, Chengdu University, Chengdu 610081, China
c.
Department of Orthopedics, The First Affiliated Hospital of Chongqing Medical University, Orthopedics Laboratory of Chongqing Medical University, Chongqing 400016, China
d.
College of Basic Medical and Forensic Medicine, Henan University of Science and Technology, Luoyang 471023, China
Received Date:
05 February 2024 Accepted Date:
23 September 2024 Revised Date:
19 September 2024 Available Online:
15 July 2025
Abstract:
Vascular stents play an important role in the minimally invasive treatment of vascular diseases, such as vascular stenosis, vascular aneurysm, vascular dissection and vascular atherosclerotic plaque disease. Bare metal stents were initially fabricated; however, the incidence of complications such as thrombosis, inflammation, restenosis, vascular injury, displacement and endoleakage is still high after implantation. To overcome these complications, several strategies for designing functional vascular stents have been carried out. Drug-eluting stents, biodegradable stents and bionic stents were manufactured and investigated. This review aims to comprehensively analyze the vascular diseases suitable for stent implantation treatment, tissue reactions after implantation, the materials and manufacturing techniques used to fabricate vascular stents, the various application scenarios in which they could be used to treat vascular lesions and the development process of vascular stents. Future development trends of vascular stents are expected to prioritize their performance, biocompatibility, and clinical accessibility. The design of vascular stents may be transformed or improved to better fulfill the rehabilitation requirements of vascular disease patients. Finally, various application scenarios may be used to treat vascular or even nonvascular diseases via endovascular access.
Vascular disorders, such as vascular stenosis and vascular dilation, cause the leading number of deaths annually and one of the highest disease burdens worldwide [1,2]. Vascular stents play a vital role in minimally invasive treatment of vascular disorders, such as expanding vascular stenosis, preventing vascular rupture and preventing atherosclerotic plaque detachment [3,4]. According to statistics, a growing elderly population will occur in both developed and developing countries. Given that many vascular disorders are aging-related diseases, the prevalence of vascular disorders is expected to increase. Moreover, the greater number of elderly patients harboring vascular disorders indicates a greater demand for minimally invasive treatment implemented by vascular stents [5].
This review provides a comprehensive and systematic overview of the various types of vascular stents used across different systems in the human body. This systematic summary covers several critical vascular systems, including coronary arteries, cerebrovascular, renal arteries, peripheral arteries, and veins, offering a detailed analysis of the design, materials, functionality, and clinical performance of each stent type. This thorough review offers researchers and clinicians a clear panoramic perspective, enabling them to better understand and select the most appropriate stent type to address specific clinical needs.
Vascular stents are mainly used for the following reasons.
(a) Coronary artery stenosis or occlusion: Coronary artery stents and peripheral vessel stents are mainly used to expand or surpass the lesion and thus to provide sufficient blood supply to the distal part of the vessel [6,7].
(b) Aortic dissection or aortic aneurysm: The aortic stent serves as a device for occluding the lesion of the artery and providing a channel to guarantee blood flow, which could prevent rupture of the aorta [8].
(c) Peripheral vessel stenosis or occlusion: Peripheral vascular stents, including stents expanding the narrow lesion of the vessels, such as carotid artery stenosis, renal artery stenosis, critical limb ischemia and venous obstruction [9,10].
(d) Carotid artery atherosclerotic plaque: The carotid artery embolic prevention stent is composed of a skeleton and covered layer, which could ensure vessel conformability and embolic protection [11].
(e) Cerebral artery dissection or aneurysm: A cerebral artery stent could ensure the patency of the cerebral artery and achieve diversion of the blood flow within the dissection or aneurysm, which is beneficial for thrombus formation within the aneurysm [12].
Vascular stents are implanted into patients via peripheral vessels, such as the femoral artery, radial artery, axillary artery or peripheral vein, to achieve interventional therapy [3]. This kind of intervention causes less injury to patients and is associated with a simpler operative procedure and shorter rehabilitation duration than open surgery. However, complications such as restenosis, thrombosis, vessel injury, endoleak, displacement, fracture and infection may occur after vascular stent implantation.
Vascular stents are usually composed of a skeleton and covered membrane if necessary. The skeletons are usually made of alloys (such as cobalt-chromium alloy, stainless steel, nickel-titanium alloy, magnesium alloy and iron alloy) or synthetic polymers (such as poly(lactic-lactic acid), PLLA and poly(lactic-co-glycolic acid, PLGA). The most commonly used covered membranes are poly(ethylene terephthalate) (PET) and expanded polytetrafluoroethylene (e-PTFE) [4,13,14].
Conventional vascular stents aim to expand or occlude the lesion of the vessel and make the vessel patent; these stents are usually fabricated with inert materials. Unfortunately, conventional vascular stents may be confronted with complications after implantation, such as thrombosis, inflammation, restenosis, vascular injury, displacement and endoleakage [15,16]. Functional vascular stents, such as drug-eluting stents, bioabsorbable stents, or tissue-engineered stents, are designed to reduce or overcome the complications that may be caused by conventional vascular stents [13,17,18].
This overview aims to summarize the progress in research on functional stents for treating vascular disorders. Our focus centers on vascular disorders treated by vascular stents, tissue reactions and related complications after stent implantation, manufacturing strategy and functional vascular stents for various vascular diseases that are commercially available or still under investigation. This study provides a summary and speculates on future research patterns to address various vascular disorders, such as drug release during balloon dilatation, bioabsorbable stents, bioabsorbable occluders and 3D printing techniques.
2.
Pathogenesis of diseases suitable for vascular stents
A vascular stent is a device that is used to treat stenosis, occlusion or dilatation disorders of vessels by intervening to deliver it to a blood vessel and keeping it open to restore blood flow. The vascular stenting procedure usually consists of the following steps: the doctor punctures an artery in the arm or leg of the patient, inserts a catheter, and guides it to the target site along the vessel. The catheter tip had a balloon covered with a metal mesh stent. The doctor then uses X-rays or other imaging techniques to locate the stenosis or occlusion in the vessel and position the balloon and stent. The doctor inflates the balloon, which expands and pushes the stent against the vessel wall while compressing the plaque and increasing the vessel lumen. The doctor deflated and removed the balloon and catheter, leaving the stent secured inside the vessel to support and maintain blood flow [19,20].
Vascular stents are mainly used in the following aspects, which are shown in Fig. 1. Vascular narrowing or stenosis: hypertension, diabetes, and hyperlipidemia can lead to the deposition of lipids and the development of atherosclerosis by causing endothelial damage and the intervention of inflammatory substances that allow the deposition of lipids. Atherosclerosis is initiated by endothelial activation, followed by a series of changes, including lipid formation, fibrous element formation and calcification, which trigger vascular narrowing and activation of inflammatory pathways. Atherosclerosis is initiated by endothelial activation, followed by a series of changes, including lipid accumulation, fibrous element formation and calcification, which trigger vascular narrowing and activation of inflammatory pathways [21]. The resulting atherosclerotic plaques, as well as the progression process, may lead to vascular complications [22]. Vascular tumors can also cause stenosis by compressing the vessel or causing structural changes [23]. Stenosis may also occur due to intimal hyperplasia and fibrosis or exogenous compression of musculoskeletal structures [24]. In addition, congenital stenosis may also be caused by fibromuscular dysplasia, where fibrous tissue develops like a spider web in the arterial wall, eventually leading to arterial stenosis [25]. The main treatment options for stenosis are medication, stent intervention, and surgery. Pharmacological treatment is an appropriate treatment option for asymptomatic patients, and the fact that some lipid-lowering and antihypertensive drugs can reduce carotid intima-media thickness and/or stabilize carotid plaque justifies the use of pharmacological treatment for atherosclerosis [26]. However, the results of the trial by Michael D. Walker showed that the overall risk of ipsilateral stroke and any perioperative stroke or death within 5 years in patients with asymptomatic carotid stenosis was 5.1% (surgically treated patients) and 11.0% (patients treated with aspirin medication), respectively [27]. For surgical treatment and stenting interventions, the trial by William H Brooks et al. was designed to explore the following: the long-term protection against ipsilateral stroke provided by carotid angioplasty stenting (CAS) and carotid endarterectomy (CEA) did not differ in this trial, which showed that among symptomatic or asymptomatic patients randomly assigned to the CEA, the risk of fatal/nonfatal heart disease attack was significantly greater [28]. In summary, conventional drug therapy usually requires long-term administration of the drug, which can cause adverse reactions or drug interactions and has limited efficacy in maintaining the patency of vessels in certain types of CVD, such as coronary atherosclerotic heart disease and aortic aneurysm, if the occlusion is severe [29]. In contrast, surgical treatments, such as coronary artery bypass grafting (CABG), are invasive open surgeries that usually require the use of extracorporeal circulation and are associated with increased risk and complications, such as blood cells damage, stroke, renal insufficiency and infection. Moreover, after surgery, patients still need to take anticoagulants and other medications to prevent thrombosis and arterial restenosis [30]. Therefore, stent intervention plays an effective and vital role in the minimally invasive treatment of vascular diseases.
Figure 1
Figure 1.
The application of stent implantation in various vascular diseases across different parts of the body. It covers common vascular conditions such as cerebral artery, carotid artery, renal artery, coronary artery, aorta, lower limb arteries, and venous obstructions, highlighting the critical role of stents in treating these areas. This review systematically elucidates, for the first time, the clinical applications of stents in improving blood flow and preventing complications, providing a comprehensive reference for the widespread use of vascular stents.
Atherosclerosis is the main cause of arterial stenosis and can affect various arteries, such as the coronary, cerebrovascular (carotid included), renal, and peripheral arteries. Disease involves the interaction of endothelial cells, leukocytes, and smooth muscle cells in the arterial wall [31]. Atherosclerosis is triggered by various risk factors, such as hypertension, diabetes mellitus, smoking, hypercholesterolemia, genetic predisposition, infections, and elevated homocysteine. These factors induce endothelial dysfunction by activating proinflammatory and prothrombotic pathways.
2.2
Rupture-type diseases
Aortic aneurysm, a localized enlargement of the aorta exceeding 50% of its normal diameter, is the second most common aortic disease after atherosclerosis. Aortic aneurysms can be classified as thoracic (TAA) or abdominal (AAA) with distinct pathophysiology [32]. AAA is characterized by medial degeneration, matrix metalloproteinase (MMP) imbalance, and intense inflammation [33,34]. TAAs are associated with extracellular matrix abnormalities and genetic variants in SMC contractile proteins [35,36]. Inflammation is also involved in TAA, but related data are scarce.
Coronary artery aneurysm (CAA) is a focal dilation of a coronary artery exceeding 1.5 times the diameter of the adjacent normal segment and is caused mainly by atherosclerosis [37]. Hyalinization, lipid deposits, calcification, fibrosis, and cholesterol crystals impair the elasticity of the vascular wall, resulting in reduced vascular resistance to pressure in the blood stream and aneurysm formation [38,39].
2.3
Stenosis combined with rupture type
The aorta, the largest artery in the body, has four anatomical segments: the ascending aorta, the aortic arch, the descending thoracic aorta, and the abdominal aorta. The integrity of the aortic wall can be impaired by preexisting conditions (such as atherosclerosis) or acquired factors. Aortic dissection, a tear in the intimal layer of the aortic wall, is more prevalent in the ascending aorta than in other segments [40]. Aortic dissection allows blood to enter the media, causing intramural hematoma and weakening of the aortic wall. In addition, intramural hematomas or bleeding from the aortic wall have been associated with aortic coarctation [41]. Expansion of the false lumen of the vessel compresses the true lumen, causing the aorta to narrow and the blood supply to the distal part of the involved aorta to be reduced or interrupted. In the context of endovascular treatment for aortic dissection, innovative design approaches hold promise.
2.4
Plaque shedding category
Carotid artery atherosclerotic plaque disease, a condition caused by fatty deposits (plaques) in the blood vessels that supply the brain (carotid arteries), is a product of atherosclerosis. Plaque lesions become more complex over time and exhibit calcification, neovascularization, fibrous cap thinning, and rupture. Fibrous cap strength depends on the balance of pro- and anti-inflammatory cytokines in the plaque, which affects plaque stability. Plaque rupture exposes thrombogenic lipid cores to blood with platelets and clotting factors, increasing the risk of thrombosis [42].
3.
Tissue reactions and related complications after stent placement
Vascular stent skeleton materials play an important role in vascular interventions. The choice of skeleton material directly affects the mechanical properties, biocompatibility, and long-term success of the stent [43]. Currently, common vascular stent materials include cobalt-chromium alloy, stainless steel, nickel-titanium alloy, and biodegradable materials. The tissue reactions and complications after vascular stent implantation are shown in Fig. S1 (Supporting information).
3.1
Inflammatory response, thrombosis and restenosis
Inflammation is a major contributor to various complications after stent implantation. Stent implantation causes damage or loss of vascular endothelial cells, exposing the basement membrane and smooth muscle cells of the vessel wall. This triggers the activation of blood cells, such as platelets, monocytes, and neutrophils, and the release of various proinflammatory mediators, such as platelet-activating factor, interleukin-1β, interleukin-6, and tumor necrosis factor-α [44,45]. These mediators further amplify the inflammatory response.
Thrombosis is a serious complication of inflammation after stent implantation. Inflammation enhances platelet adhesion and aggregation, which are essential for thrombus formation. Platelets adhere and aggregate on the damaged vessel wall, releasing procoagulant and proinflammatory mediators [46], which enhances blood coagulation and inflammation, leading to thrombus formation [47-49]. Furthermore, stent implantation alters hemodynamics, leading to blood flow disturbances that stimulate platelet activation and aggregation [50].
Despite improvements in stenting technology, in-stent restenosis (ISR), which is defined as stenosis of > 50% within or near the previous stent site, can cause a reduction in vessel lumen diameter after angioplasty. The ISR is the main cause of target lesion failure after percutaneous coronary intervention (PCI) and might still occur in as many as 2%–10% of PCIs [16]. ISR typically presents in two patterns: one peak within 6–8 months after stent implantation and is associated with excessive intimal hyperplasia; the other occurs after 2 years or longer and is related to de novo atherosclerosis. The incidence and timing of ISR vary according to the type of stent, the nature of the lesion, and the baseline characteristics of the patient [51,52].
3.2
Vessel damage, stent displacement, fracture, and endoleak formation
Endovascular stent implantation and antiproliferative drug release can damage the vascular endothelium [15]. Stent implantation impairs the integrity of the endothelium due to mechanical stimuli such as friction, tensile stress, and compression from balloon expansion and stent placement, while the vascular elastic plate exposed to the blood is susceptible to platelet and blood constituent adhesion and activation, leading to thrombus formation [53]. Moreover, insufficient stent expansion, polymer fracture, and the metal stent itself can elicit inflammatory responses and damage the endothelium [15].
Stent migration, the displacement of a stent from its original position to another site in the vascular system, can cause vessel restenosis or occlusion and lead to serious complications such as myocardial infarction or aortic dissection. Several factors may contribute to stent migration, including: (1) Technical factors during stent placement; (2) biological factors after stent placement; and (3) pharmacological factors after stent placement [54,55].
A stent fracture is the partial or complete disruption of a stent's structural integrity after implantation. It can be caused by factors related to the stent, such as material corrosion or wear, or factors related to the implantation, such as technique, vessel anatomy, hemodynamics, or stent underexpansion or edge dissection [56,57]. There are five types of stent fractures: type Ⅰ, with a single strut; type Ⅱ, with multiple struts at different locations; type Ⅲ, with multiple struts and a complete transverse fracture without displacement; type Ⅳ, with a complete transverse fracture and displacement; and type Ⅴ, with a spiral fracture [58]. Angiography is the main diagnostic tool for stent fracture, but intravascular ultrasound or optical coherence tomography may be needed for confirmation. The treatment of stent fracture depends on the patient's clinical condition and the type, location, and severity of the fracture [59].
Endoleak, a complication of stent implantation, is defined as persistent blood flow between the stent and vessel wall or within the stent components, which maintains aneurysm sac perfusion and increases the risk of aneurysm rupture. Endoleaks are classified into five types according to their origin [60]. (1) Type Ⅰ endoleak is caused by an inadequate seal between the stent and vessel wall at the proximal or distal end, which may be related to the length, diameter, angle, and texture of the aneurysm neck; (2) type Ⅱ endoleak is caused by retrograde blood flow from collateral vessels such as lumbar or inferior mesenteric arteries that remain patent after stent placement and are the most common and usually benign; (3) type Ⅲ endoleak is caused by defects within the stent due to poor or misaligned connections, separation or displacement of modules, or damage or deformation of the stent itself, which are serious and may lead to a sudden increase in intrasac pressure; (4) type Ⅳ endoleak is caused by excessive porosity of the stent fabric due to material characteristics or the manufacturing process, which are transient and usually resolve within 30 days; and (5) type Ⅴ endoleak, which refers to an increase in maximum aneurysm diameter with no identifiable causes [60-63].
3.3
Stent infection
Stent infection is rare but has a high mortality rate [64]. Stent infection may result from several factors: contamination of the catheter or stent surface by microorganisms during stent placement, which may infect the vessel wall; immunosuppression utilization after stent placement, may increase the vulnerability of the vessel wall to bacterial or fungal invasion; bleeding induced by anticoagulant medication after stent placement, which may predispose the vessel wall to infection; or concomitant infections in other body parts, which may disseminate bacteria or fungi to the stented vessel through the bloodstream. Biofilm formation or drug resistance in microorganisms after stent placement may render conservative treatment ineffective [65-67].
4.
Materials and manufacturing techniques
The design, material selection, and preparation of vascular stents is a complex and critical process that directly impacts patient outcomes and quality of life. The design consideration is to ensure that the stent is accurately adapted to the patient's vascular characteristics and lesions. Through rational shape, size, and structural design, the stent can provide the necessary mechanical support and maintain smooth blood flow. The choice of materials takes into account the mechanical requirements, biocompatibility, and long-term biostability of the stent to ensure stability and safety in vivo. The preparation process needs to ensure the accuracy of the stent's geometry and dimensions. Through rational design, quality material selection, and precise preparation, vascular stents can provide effective treatment and improve patient quality of life. This not only has a direct impact on patient recovery and health but also drives continuous progress and innovation in the field of vascular disease treatment. Fig. S2 (Supporting information) illustrates the stent materials, design and manufacturing techniques.
Vascular stents are classified as self-expanding stents and balloon-expandable stents according to their unfolding pattern after implantation. Self-expanding stents are cardiovascular devices that do not need balloon dilation and use their inherent shape-memory and elasticity to automatically expand and adapt to vessel walls after deployment at stenotic sites [4,68]. Self-expanding stents are simple to operate and versatile and can accommodate the curvature and deformation of blood vessels. The main material of self-expanding stents is nickel-titanium alloy, also known as nitinol, which is a superelastic and biocompatible metal alloy that can retain a stable shape at various temperatures. Self-expanding stents, typically in the form of a mesh or helix, provide adequate radial force and flexibility. Self-expanding stents can adjust to changes in the vessel to prevent overexpansion or overcompression, reducing the risk of vessel injury and stent displacement [69-71].
Balloon-expandable stents are cardiovascular devices that are delivered to the target site through a balloon catheter and then inflated to the appropriate diameter by the balloon; then, the balloon catheter is withdrawn, leaving the stent fixed in the vessel [72]. The main materials used for balloon-expandable stents include stainless steel, cobalt-chromium alloy, and platinum-chromium alloy, among others [13,70]. These metal materials have high strength and corrosion resistance and can resist the pressure of balloons and blood erosion. The procedure of balloon-expandable stent implantation involves the following steps: The stent is first fabricated to a size slightly smaller than the diameter of the blood vessel and then crimped and mounted on a balloon catheter, which is advanced through the catheter to the lesion site. The balloon is pressurized to dilate the stent to the diameter of the blood vessel, causing the stent to undergo plastic deformation and adhere closely to the vessel wall. Because the diameter of the balloon-expandable stent can be adjusted according to the pressure of the balloon and the size and position of the stent can be precisely controlled, the risk of vascular injury and stent migration can be reduced [4,73].
4.1
Materials applied to vascular stents
Material selection for vascular stents is vital. Materials differ in their characteristics and advantages, which determine their strength, flexibility, and biocompatibility. These properties affect treatment outcomes and quality of life [74].
4.1.1
Materials applied for the stent skeleton
Vascular scaffold materials play an important role in vascular interventions. The choice of skeleton material directly affects the mechanical properties, biocompatibility, and long-term success of the stent [43]. Currently, common vascular stent materials include cobalt-chromium alloy, stainless steel, nickel-titanium alloy, and biodegradable materials.
Cobalt-chromium alloy is one of the widely used vascular stent materials. It has excellent mechanical properties and biocompatibility, provides strong support, and maintains good toughness and stability. Cobalt-chromium alloy stents have a high modulus of elasticity and stiffness, allowing the stent to resist vascular contraction and expansion with small bending deformations. Medtronic's Endeavor [74], Resolute Integrity [75,76], and Abbott Laboratories' Xcience V Primexpedition and Boston Scientific Corp's Promus element and Promus Premier are already in clinical use on a large scale [77]. However, there are limitations in the hydrophilic properties of cobalt-chromium alloys, which may lead to thrombosis or cell proliferation in and around the stent [78-81].
Stainless steel possesses good mechanical properties and provides stable support, having the advantages of high strength and rigidity. Boston Scientific Corp's Taxus Express/Liberteh and Cordis' Cypher are other common vascular stent materials made of stainless steel [82]. However, stainless steel is relatively poor in terms of biocompatibility, which can lead to inflammatory reactions and thrombosis. In addition, the high modulus of elasticity and density of stainless steel stents may limit their adaptability and unfolding [83-87].
Nitinol is a material with shape memory and superelasticity that can adapt to the physiological movement of blood vessels. Nitinol stents have a low modulus of elasticity and high plasticity, which allows them to maintain stable support under changes in vessel diameter. However, nitinol still presents some challenges in terms of biocompatibility and processability, such as the possibility of triggering allergic reactions and limiting the manufacturing process [88-94].
Biodegradable materials are commonly used to fabricate the skeleton of vascular stents with the characteristics of degradability and biocompatibility in biomedical fields such as tissue engineering, drug delivery, medical devices, etc. They usually include metal absorbable materials and polymer absorbable materials.
Metal absorbable materials are metals that corrode in physiological environment and are intended for temporary medical implant applications. The main types of metal absorbable materials are iron, magnesium, zinc, and their alloys. These metals have different corrosion rates and mechanical properties and can provide structural support and stimulate bone healing [95,96]. Iron alloy scaffolds are a novel type of biodegradable cardiovascular scaffold comprising iron and its oxides or drug coatings. These scaffolds modulate SMC and human umbilical vein endothelial cell (HUVEC) activity depending on the concentration and generate impurities after degradation. Iron and its alloys exhibit good mechanical properties and biocompatibility [97-99].
Polymer absorbable materials, such as polyvinyl alcohol (PVA), polycaprolactone (PCL), polylactic acid (PLA), poly-l-lactic acid (PLLA), are polymers that can absorb and retain large amounts of water or other liquids relative to their own mass. These polymers are also called superabsorbent polymers (SAPs) or hydrogels and are usually cross-linked to prevent dissolution [100]. Poly(lactic acid)-trimethylene carbonate (PLLA-TMC) is a biodegradable binary polymer with shape memory function, which enables it to self-rebound and expand after implantation in the human body. It also exhibits surface dissolution, which lowers the risk of fracture during the degradation of PLLA scaffolds. By incorporating TMC, the mechanical properties of PLLA can be enhanced and modulated. PLLA-TMC has good strength, high elongation at break, and high tensile modulus. Moreover, the degradation products of TMC are neutral, which reduces the acidity and the inflammatory potential of the copolymer. These properties make PLLA-TMC a promising candidate for the coronary stents, aortic stent skeleton or cladding material [101].
The advantages of biodegradable materials include the ability to gradually restore and re-establish the natural function of blood vessels, avoiding long-term side effects and sequelae. However, the current challenge is to find suitable materials and design a degradation rate for stents to match the degradation process of the stent with the healing process of the vessel [102-104]. Magnesium and PLLA stents have different modes of absorption after implantation. Magnesium stents form amorphous calcium phosphate at the stent-vessel interface, which is deposited in the vessel wall, whereas PLLA stents degrade into carbon dioxide and water, which are eliminated from the body without leaving any residual material on the vessel wall [105].
To conclude, vascular stent materials have distinct strengths and drawbacks. Cobalt-chromium alloys and stainless steels exhibit excellent mechanical properties but suffer from poor biocompatibility. Conversely, nitinol possesses shape memory and superelasticity to accommodate the physiological movement of blood vessels, but its biocompatibility and processability remain challenging. Biodegradable materials, as novel vascular stent materials, can gradually degrade and promote revascularization, but the trade-off between degradation rate and material properties requires further optimization [101]. Therefore, when selecting vascular stent materials, patient-specific conditions, therapeutic needs, mechanical properties, biocompatibility, and degradability need to be considered. With the continuous development of medical science and technological advances, additional options for vascular stent materials may emerge in the future to improve the efficacy and safety of vascular interventions. Moreover, continuous improvements in material properties and design will drive the development of vascular stent technology.
4.1.2
Stent coating-related materials
Vascular stent coating materials play an important role in vascular interventional therapy to fabricate a functional vascular stent. Coating materials can improve the biocompatibility, antithrombotic, and drug-release properties of vascular stents, thus improving the therapeutic effect and reducing the complication rate.
Polymer materials are widely used as coatings for vascular stents because of their tunable surface properties and biocompatibility. Commonly employed polymers include PLLA [106-109], PCL [110-112], polyhydroxyacetic acid (PHEA) [113,114], and expanded polytetrafluoroethylene (e-PTFE) [115]. These materials have adjustable dissolution rates and degradable properties so that the rate and duration of drug release can be controlled. It is also possible to combine a drug with a polymer, which has dual effects [116]. The polymer carrier facilitates the slow release of the drug, maintaining a sustained drug concentration and therapeutic effect. Moreover, the polymer coating enhances the biocompatibility and histocompatibility of the stent and reduces thrombosis and inflammation. Typical examples of drug‒polymer composites include polylactic acid–drugs and polycaprolactone–drugs [117-120].
Covered stents are a technique used to improve the compatibility of stents with vessel walls. The main purpose of covering is to isolate the lesion and to achieve overall diversion of blood flow [121]. The covering can also limit further expansion of the stent skeleton so that the skeleton implanted in the human body has outward elasticity and an inward restrictive force on the covering. This characteristic mimics the natural elasticity of human blood vessels [122]. A covered stent can reduce the stress on the vessel wall and minimize vessel damage. A smooth covering can also reduce thrombosis. Stent covering materials should have good biocompatibility, mechanical properties, antithrombotic properties, anti-infection properties and drug delivery capabilities. Two prevalent stent covering materials are e-PTFE and PET. However, there are drawbacks to covered stents, as some covering materials may affect the endothelialization of vascular stents and increase the risk of inflammation, thereby increasing the rate of restenosis.
4.2
Manufacturing techniques
Vascular stents, which are medical devices that treat blocked or narrowed blood vessels, consist of metal alloys or polymers with a mesh-like structure that can expand inside the vessel. The manufacturing process for cardiovascular stents comprises three stages: design, fabrication, and post-processing. These stages employ various techniques, such as laser cutting, electrochemical machining, microelectric discharge machining, 3D printing, additive manufacturing, weaving, electrospinning, and coating. These techniques enable the creation of complex and precise geometries, the enhancement of surface quality, biocompatibility, and drug delivery, and the provision of features such as degradability and tissue regeneration, depending on the clinical requirements and the mechanical properties of the material. Manufacturing technologies for vascular stents are constantly evolving to address the challenges and demands of the medical fields.
4.2.1
Additive manufacturing
Additive manufacturing is a process of creating objects by adding material layer by layer. This process is widely used in the fabrication of vascular stents, which requires precise control over the shape and structure of the final product. Two common additive manufacturing techniques are laser-based directed energy deposition (DED) and 3D printing, which enable the formation and curing of layers of suitable materials according to the design specifications [43].
Stent coating technologies enhance the biocompatibility of stents and reduce the risk of postimplantation complications, including endothelial hyperplasia, thrombosis, and vascular injury. These technologies involve coating the stent surface with different materials or drugs that can modulate stent–blood and stent–vessel wall interactions, regulate drug release kinetics, enhance the mechanical properties of the stent, and promote endothelialization and vascular repair.
Drug-eluting stents (DESs) are the most widely used functional vascular stents in clinical practice. Polymer coatings that contain anti-proliferative drugs, such as paclitaxel, sirolimus, or everolimus (Fig. S1), are locally released around stents to inhibit the excessive proliferation of smooth muscle cells and reduce the incidence of ISR [123].
To accelerate the endothelialization of stents, several researchers have explored the use of mussel protein coatings, which are bionic materials that mimic the adhesive properties of mussels. This coating has good biocompatibility and antimicrobial properties and can reduce the risk of infection by inhibiting bacterial adhesion and biofilm formation. Moreover, it can serve as a drug carrier to immobilize drugs or growth factors that facilitate endothelialization, such as vascular endothelial growth factor, nitroglycerin, or heparin, on the stent surface [124].
Another promising functional cardiovascular scaffold is the hydrogel coating, which resembles the extracellular matrix environment and provides good biocompatibility and mechanical properties. Hydrogel coatings can be physically or chemically attached to the scaffold surface by methods such as electrostatic adsorption, covalent bonding, or metal coordination [125]. The rate and duration of drug release can also be controlled by adjusting parameters such as the degree of cross-linking, porosity, and water content. Furthermore, they can be combined with different drugs or growth factors, such as heparin, aspirin, dopamine or vascular endothelial growth factor, to achieve anticoagulation, anti-inflammatory, and endothelialization effects [126].
Heparin-coated stents have a surface layer of heparin, an anticoagulant and anti-inflammatory agent that can be immobilized by electrostatic adsorption, covalent bonding, or polymer carriers. These stents can inhibit platelet adhesion and activation, thereby reducing thrombus formation and suppressing the adhesion and infiltration of inflammatory cells, thereby attenuating the inflammatory response. Five clinical studies have shown that heparin-coated stents can lower the incidence of ISR and improve the long-term outcomes of stenting [127].
Dopamine-coated stents have a surface layer of dopamine, a biogenic amine that can spontaneously polymerize on metal surfaces under neutral or alkaline conditions. These stents have excellent biocompatibility and bioactivity, which enable them to inhibit platelet adhesion and activation, reduce thrombus formation, and act as carriers for drugs or other biological factors, thus achieving multifunctional stent design [128].
(1) Laser engraving and laser sintering.
Laser engraving and laser sintering are commonly used additive manufacturing methods in the manufacture of vascular stents, and they play important roles in realizing the microstructure and complex shape of vascular stents [43].
Laser engraving is a technique that uses a laser beam to etch or cut the surface of an object and fabricate microstructures of vascular stents. This technique offers several benefits and applications in vascular stent manufacturing. It facilitates cell attachment, proliferation, and tissue regeneration by creating microscopic pores that increase the attachment area and enable nutrient delivery [129]. In addition, it mimics the microstructure of natural blood vessels and guides the directed growth of vascular endothelial cells and smooth muscle cells to promote vascular regeneration and repair. Laser engraving technology also enables the controlled release of drugs, optimizing drug delivery and therapeutic effects by modulating the pore structure [130]. The success of laser engraving depends on the accurate control of the laser beam parameters, such as power, pulse frequency, and scanning speed. These parameters can be adjusted to achieve the formation of different pores and textures to meet specific stent design requirements.
Laser sintering, on the other hand, enables the fabrication of complex vascular stents by fusing metal powders heated by a laser beam and stacking them layer by layer to form a three-dimensional structure. This technique can be applied to a wide range of metallic materials, such as titanium alloys, stainless steel, or nickel-titanium alloys, to achieve the desired mechanical properties and biocompatibility [88,131,132]. The primary challenge in the manufacture of cardiovascular stents using laser engraving and laser sintering is achieving the necessary precision and consistency to prevent structural instability and material damage. Additionally, while femtosecond laser technology allows for precise cutting without thermal damage, it is costly and requires complex operation [133,134].
(2) 3D printing.
3D printing is a manufacturing technology that creates three-dimensional structures by layering materials. In vascular stent manufacturing, 3D printing can be used to directly print the stent structure or print a prototype mold of the stent [135,136]. A 3D model of the vascular stent was created using computer-aided design software to determine its size, shape, and structural features. The design process takes into account the specific needs and material requirements of the stent. Next, appropriate printing materials, such as biodegradable polymers or metal alloys, are selected. Material selection depends on the purpose and biocompatibility of the vascular stent, as well as the mechanical and degradation properties it should have. Then, the 3D printing device is prepared, and the selected printing material is loaded into the device. The print parameters, such as the temperature, print speed, and layer height, were set. The printing platform was calibrated to ensure accuracy and stability [137-139].
3D printing can use a variety of materials, such as metal powders and biodegradable materials, to achieve complex geometries and pore structures. For metallic stents, highly customizable, adjustable, and biocompatible stent structures can be achieved using 3D printing [138-143].
In addition, 3D printing can be combined with other techniques, such as laser engraving and coating, to further improve the performance and functionality of the stent. 3D printing has become an important method in the field of vascular stent manufacturing due to its advantages of manufacturing flexibility, customizability and rapid response to production needs [112-144].
Laser engraving, laser sintering, and 3D printing are important methods for additive manufacturing of vascular stents. These methods have advantages, such as personalization, microstructure control, and complex geometry manufacturing, and provide new opportunities for the research and application of vascular stents. Three-dimensional (3D) printing technology holds significant promise for the fabrication of cardiovascular stents, particularly in the context of personalized therapy. Nevertheless, the production process for 3D-printed stents is time-consuming, posing challenges for their rapid deployment in acute conditions such as aortic dissection, where timely intervention is critical [143,144].
4.2.2
Weaving
Weaving is a commonly used method for preparing vascular stents by weaving fibrous materials to form stents with mesh structures. Different fibrous materials, such as metal wires and polymer fibers, can be used in this method [145].
Weaving, as a traditional method of vascular stent preparation, has the advantages of excellent flexibility and mechanical strength, low preparation cost, suitability for large-scale production, and the ability to use a wide range of fiber materials. However, its drawbacks include a denser stent structure with possible unenclosed gaps, increasing the risk of thrombosis and restenosis, as well as higher demands on the processability of certain fiber materials with possible material handling and fiber breakage problems [146,147].
4.2.3
Electrospinning
Electrospinning is an emerging preparation method in which electrostatic force and surface tension are used to prepare polymers in solution or in the molten state to form fibrous structures.
Owing to the manufacturing process of electrospinning, which is highly controllable and tunable, fibers with micro- and nanoscale dimensions can be prepared, and the shape, diameter, and porosity of the fibers can be regulated. Electrospinning also has good drug-carrying properties, and by adding drug-carrying carriers to solution, drugs can be uniformly wrapped on the surface or inside fibers to achieve controlled release and local release, thus effectively treating vascular diseases. In addition, electrospinning has good biocompatibility, and its biocompatibility and biodegradability can be considered when choosing suitable polymer materials to reduce irritation and side effects on blood vessels [148,149].
However, electrospinning has several challenges and limitations in vascular stent preparation. On the one hand, drugs may be affected by the high-voltage electric field, solvent volatilization, and curing treatment during electrospinning, leading to a decrease in drug stability. On the other hand, stents prepared by electrospinning may have several limitations in terms of their mechanical properties, such as strength, toughness, and plasticity, which need to be further optimized. In addition, the electrospinning preparation process is relatively slow and requires precise control of multiple parameters, resulting in relatively low preparation efficiency [150-153]. Ensuring the mechanical properties and biocompatibility of cardiovascular stents through electrospinning necessitates precise control over fiber diameter and uniformity, thereby increasing process complexity and operational difficulty. Additionally, the use of organic solvents in electrospinning poses toxicity risks, exacerbating environmental and operational safety challenges [153-156].
Overall, electrospinning has great potential in vascular stent preparation, with advantages including size tunability, drug-carrying properties, biocompatibility, and structural diversity. Despite some challenges and limitations, with further research and optimization of the process, electrospinning may become a promising preparation method for treating vascular lesions.
4.2.4
Fabrication of covered layer of vascular stents
Cardiovascular stent covered layer material is a material that covers the surface of a stent, which is a metal mesh device that is inserted into a narrowed or blocked artery to restore blood flow. The overlay material can improve the biocompatibility, hemocompatibility, and drug delivery of the stent, and prevent complications such as thrombosis, inflammation, and restenosis [157].
There are different methods to prepare cardiovascular stent overlay material, depending on the type of material and the desired properties. Some common methods are:
Coating: This method involves applying a thin layer of material, such as polymer, drug, or peptide, onto the stent surface using techniques such as dip coating, spray coating, electrospinning, or plasma deposition [158,159]. For example, polymer coating is a common method to deliver drugs or bioactive molecules to the stent site, such as paclitaxel, rapamycin, or estradiol. Polymer coating can also improve the biocompatibility and hemocompatibility of the stent material and reduce the risk of thrombosis and inflammation. Some of the polymers used for coating include PLGA, poly(ethylene-co-vinyl alcohol) (EVAL), and poly(trimethylene carbonate) (PTMC) [159,160].
Surface modification: This method involves altering the surface properties of the stent material, such as roughness, wettability, or functional groups, using techniques such as etching, oxidation, or grafting [159]. Peptide conjugation is a method to modify the stent surface with specific peptides that can promote the adhesion and growth of endothelial cells, such as Arg-Glu-Asp-Val (REDV), Arg-Gly-Asp (RGD), or Tyr-Ile-Gly-Ser-Arg (YIGSR). Peptide conjugation can enhance the endothelialization of the stent and prevent restenosis. Some of the techniques used for peptide conjugation include covalent bonding, electrostatic adsorption, or layer-by-layer assembly [96].
Alloying: This method involves mixing different metals or elements to form a new stent material with improved mechanical, chemical, or biological properties [158]. Magnesium alloying: This is a method to create a new stent material that is biodegradable and absorbable by the body, eliminating the need for long-term implantation. Magnesium alloying can also improve the mechanical properties and corrosion resistance of the stent material and provide beneficial effects on vascular remodeling and healing. Elements used for magnesium alloying include zinc, yttrium, neodymium, zirconium, and rare earth metals.
4.3
Methods of coating surface modification of vascular stents
Conventional vascular stents are prone to thrombosis, restenosis, and endoleak after long-term use. To address these issues, researchers have developed various vascular stent surface modification strategies to enhance the biocompatibility, antithrombotic properties, and therapeutic efficacy of stents. Fig. S3 (Supporting information) illustrates the surface modification strategies for vascular stents.
4.3.1
Mechanical treatment
Mechanical treatment is a technique for modifying surfaces using physical mechanics. Common mechanical treatments include polishing, scraping, and sandblasting. These treatments remove surface defects and contaminants, resulting in a smoother surface with less mechanical irritation and platelet activation. In addition, mechanical treatments can improve the surface roughness of vascular stents and increase their surface area, which facilitates cell attachment and biomolecule adsorption [138,161].
4.3.2
Physical treatment
Physical treatment is a method of modifying the surface of vascular stents using physical properties. Common physical treatment techniques include sputter coating, ion implantation, and plasma treatment. Through these methods, a thin film can be formed on the surface of a vascular stent, or the chemical composition of the surface can be changed, thus altering the surface properties and functions of the stent [162-164].
4.3.3
Chemical treatment
Chemical treatment is a technique that utilizes chemical reactions to modify surfaces. Common chemical treatments include acid‒base treatment, polymer modification, and functional group modification. By adjusting the chemical composition and functional groups on the surface, the surface energy, hydrophilicity, and hemophilic properties of vascular stents can be altered, thereby affecting their interaction with blood and biological tissues [165-168].
4.3.4
Others
Vascular stent surface modification methods may also utilize bioactive substances. For example, growth factors can be coated on the stent surface to promote the proliferation and repair of vascular endothelial cells. This helps accelerate the vessel healing process and reduce the risk of restenosis. In addition, antibiotics can be utilized to prevent stent infections [169-172]. The application of nanotechnology in surface modification allows for the preparation of structure-specific nanomaterials and coatings that increase the surface area and roughness and improve cell attachment and biological interactions [173]. However, the safety and preparation process of nanomaterials still need to be further evaluated and optimized to ensure reliability and safety in clinical applications [174-177].
In conclusion, these applications provide new ways to improve the biocompatibility, functionality, and personalized medicine of vascular stents. These methods can alter the properties of vascular stents, thereby improving their biocompatibility and functionality. Future studies need to explore more advanced surface modification methods and perform more in-depth research on the modification effects and underlying mechanisms to promote the development and clinical application of vascular stent technology.
5.
Research progress in functional vascular stent in the last 20 years
Cardiovascular stent development has three main stages: first-generation stents and bare metal stents (BMSs). These are the earliest stents made of stainless steel or other metals. They restore blood flow by propping up the stenotic vessel with balloon dilatation, but BMSs have a high restenosis rate after the procedure (approximately 20%–30%), requiring repeat angioplasty. Second-generation stents: DES. DES are based on the use of a BMS with an added drug coating, which releases antiproliferative drugs slowly to inhibit vessel lining thickening and reduce the restenosis rate (approximately 5%–10%). However, patients treated with DESs still need long-term dual antiplatelet therapy to prevent in-stent thrombosis. Third-generation stents: bioresorbable stents (BRSs). BRSs are composed of biodegradable polymers or metals that the body gradually absorbs after vessel propulsion and drug release, allowing the vessel to return to its natural state.
5.1
Coronary stent classification
Coronary heart disease (CHD) is a major cause of mortality, and coronary arterial stenosis contributes substantially to heart disease. A coronary stent is a tube-shaped device that is inserted into a narrowed or blocked coronary artery to supply blood to the heart to restore blood flow and relieve symptoms of CHD. Coronary stents are inserted by a minimally invasive technique known as PCI or angioplasty. In this procedure, a thin, flexible tube (catheter) with a balloon at its tip is guided through a blood vessel to the affected artery. The balloon was inflated to widen the artery, and a stent was placed to keep it open. Coronary stents can alleviate chest pain and myocardial ischemia caused by atherosclerosis, a condition in which fatty plaques build up on the inner walls of the arteries. Complete blockage of an artery can result in myocardial infarction or heart attack. Coronary stents can rapidly restore blood flow and reduce myocardial damage [178]. There are three main types of coronary stents: BMSs, DESs, and bioresorbable vascular scaffolds (BVSs). BMSs are simple metal mesh tubes without any coating. DESs have a thin layer of polymer that releases antiproliferative drugs into the arterial wall to prevent restenosis or renarrowing of the artery [179]. BVSs are made of bioabsorbable materials that dissolve over time, avoiding the long-term complications of permanent stents [180]. Common commercially available coronary stents are shown in Table S1 (Supporting information) [4,181-199].
5.1.1
Traditional BMS
Schematic diagram of bare metal and DES are shown in Fig. S4 (Supporting information). Coronary stenting is an effective revascularization method to treat CHD. PCI via the implantation of drug-eluting stents or BMSs is a common medical procedure. BMS implantation prevents acute vessel closure by sealing the balloon-induced intercalated flap and reduces restenosis rates by supporting the balloon to dilate the artery and preventing late retraction. Thus, coronary stents improve the procedure's safety and efficacy [192,200]. BMSs are usually made of stainless steel (316 L), cobalt-chromium (Co-Cr) or platinum-iridium (Pt-Ir) alloys, tantalum (Ta), or nickel-titanium (Ni-Ti) [186].
5.1.2
Conventional drug-eluting stents
BMS implantation has a high ISR rate of approximately 20%–30% [201], making stent technology challenging and necessitating safer solutions for patients. DESs were developed to address this problem. DESs carry drugs through polymers on the metallic stent surface and release the drug from the polymer coating to cardiovascular wall tissues in a controlled manner when the stent is placed into the intravascular lesion site, where it can exert biological effects. DES usually has three components: a stent, a stent coating, and an antistenosis drug or therapeutic agent [202]. Stents are usually made of biologically inert metals such as stainless steel; however, metal alloys such as cobalt-chromium alloys are superior to stainless steel as the material for stent design. The use of thinner stent struts reduces restenosis and mortality rates. The ideal DES-coated polymer should inhibit endothelial growth effectively, be nonthrombogenic and nontoxic to cells, and promote arterial healing through reendothelialization. The stent surface should be hemocompatible to avoid thromboembolism until vessel reendothelialization. The following four classes of drug candidates are used in DESs: anti-inflammatory, antithrombotic, antiproliferative, and immunosuppressive drugs. The main drugs used in stents are paclitaxel, sirolimus (immunosuppressive drug), tacrolimus (immunosuppressive drug), zotarolimus, tacrolimus, aspirin, citric acid, cilostazol, dexamethasone, heparin, rifampicin and everolimus [183,203].
DESs reduce the restenosis rate of vascular stents, but the metal backbone of DESs stays in vessels permanently, promoting atherosclerosis progression. A transient stent, which would keep the vessel open initially and be absorbed at the end of treatment, allowing the vessel to resume its natural state, would be the ideal solution.
5.1.3
BRSs
Biodegradable stents, which can provide temporary scaffolding and then degrade over time, are promising alternatives to conventional stents for the treatment of coronary artery disease. These stents can be divided into two main types: biodegradable metallic stents and biodegradable polymer stents. Biodegradable metallic stents include magnesium, iron, zinc, and their alloys. These materials have high mechanical strength, good biocompatibility, and essential trace element roles in the human body. Biodegradable polymer stents are composed of polymers that can degrade into biocompatible or bioresorbable products. Examples of these materials include poly(lactic acid), poly(glycolic acid), poly(caprolactone), and their copolymers. These materials have tunable degradation rates, drug delivery capabilities, and weak inflammatory responses. Fig. S5 (Supporting information) illustrates schematic diagram of bioresorbable scaffold.
5.1.4
Other functional coronary stents
CD146 antibody-modified vascular stents: CD146 is an adhesion molecule that is expressed by various cells in the vasculature, especially endothelial cells. Kwang-Sook Park and colleagues developed an advanced EPC capture scaffold coated with an anti-CD146 antibody-immobilized silicon nanofilm (SiNf). The anti-CD146 antibody-SiNf scaffold is a promising option for reducing thrombosis and restenosis through reendothelialization [204].
CD133 antibody-modified vascular stents: CD133 is a pentameric transmembrane glycoprotein that is used for labeling cancer stem cells in various tumor types. Przemysław Sareł and colleagues prepared thin films based on an ammonium acryloyldimethyltaurate and vinylpyrrolidone copolymer coated on 316 L stainless steel discs and conjugated them with a CD133 antibody for biofunctionalization [205].
CD34 antibody-modified vascular stents: CD34 is a transmembrane phosphoglycoprotein that is used for selecting and enriching hematopoietic stem cells for bone marrow transplantation. Gaku Nakazawa and colleagues tested the feasibility and efficacy of sirolimus-eluting scaffolds (SESs) with anti-human CD34 antibodies immobilized on the surface compared to those of SES alone. The results suggest that combining antiproliferative therapy with techniques to increase scaffold endothelialization is feasible and that anti-CD34 antibody surface modification enhances scaffold endothelialization when applied to SES [206,207].
Nitric oxide-releasing vascular stent: Vascular endothelial cells produce nitric oxide (NO) to maintain vasodilator tone, which is essential for regulating blood flow and pressure [208]. Lyu and colleagues developed a new layer-by-layer grafting strategy to prepare endothelial-like surfaces with dual functionality on cardiovascular stents. The bifunctional scaffolds showed effective antithrombosis in vitro, rapid endothelialization and long-term prevention of restenosis in vivo [209].
Tissue-engineered vascular stents: Tissue-engineered vascular scaffolds are artificial blood vessels made of biomaterials and cells that aim to overcome the therapeutic challenges of cardiovascular disease. Tissue-engineered vascular scaffolds use biomaterials and cells to mimic the structure and function of natural blood vessels by providing physical support and biological signals that enhance endothelialization and angiogenesis. Moreover, tissue-engineered vascular scaffolds can be customized using stem cells or other sources of cells to suit the needs of different patients and individual differences. Tissue-engineered vascular scaffolds can be fabricated by advanced technologies such as electrospinning and 3D printing for precise control and multilayer design [210-212]. However, tissue-engineered vascular scaffolds are not yet ready for clinical application, and additional research and validation are needed to evaluate their safety and efficacy.
5.2
Cerebrovascular stents
A cerebrovascular stent is a device used for the treatment of cerebrovascular disease and is made of flexible metal or fiber mesh that can be delivered through a catheter into the cerebral vasculature to support the vessel wall and prevent rupture of the blood vessel or loss of blood at the site of an aneurysm to reduce the risk of bleeding from a cerebral aneurysm or a stenosis lesion to improve the blood supply [213,214].
As technology advances, new materials and designs for cerebrovascular stents are emerging. For example, the application of 3D printing technology allows for the rapid formation of innovative, inexpensive, personalized, and rapidly reproducible arterial BRSs as well as the emergence of resorbable cerebrovascular stents in recent years [144], which degrade over time, and bioresorbable scaffolds are believed to reduce the risk of these complications. The long-term effects and side effects on the patient's body should be reduced [215]. In addition, several new materials and designs, such as biocompatible materials, adaptive materials, and other technologies for manufacturing drug-eluting stents, have been introduced into cerebrovascular stents, and these technologies have been combined with bioabsorbable scaffolds, which provides an effective approach for treating a wide variety of diseases [129,213,216,217].
Vascular stents are essential devices in the evolving field of medical intervention. They have established applications and untapped potential. One novel application is the treatment of paralysis using vascular stents in brain-computer interfaces (BCIs) [218-220]. BCIs are technologies that use electroencephalographic (EEG) signals to control external devices for patients with neurological disorders, such as paralysis, epilepsy, and Parkinson's disease [221]. BCIs work by detecting changes in EEG signals that reflect the patient's intent or state and converting them into commands to control external devices, such as prosthetics, wheelchairs, and computers. Conventional BCIs require craniotomy to implant electrodes into the cortex or deeper brain regions, which poses high risks and complications, such as infection and bleeding [222,223]. To avoid these problems, a new BCI technique uses an endovascular stent (Stentrode) as the electrode, which can be delivered through the jugular vein into the superior sagittal sinus, a large vein between the two brain hemispheres. The Stentrode records EEG signals from the motor cortex within the superior sagittal sinus and wirelessly transmits them to an implanted receiver, which then sends them to an external controller, enabling BCI function. The stent can be implanted into the brain through minimally invasive endovascular surgery without the need for craniotomy, reducing risks and complications. The Stentrode also allows long-term stable recording and transmission of EEG signals, improving the performance and reliability of the BCI [224,225]. The Stentrode also enables BCI to control stent function, such as by adjusting the stent size and shape and releasing drugs, reducing the risk of stent thrombosis and ISR.
With the advancement of technology and the accumulation of clinical experience, the design of cerebrovascular stents will become more precise, material optimized, and finely manipulated, moving toward adjustability and miniaturization. Meanwhile, they may have emerging roles of handling certain neurological disorders in the future.
5.3
Renal artery stents
Renal artery stenosis is a common disease that can lead to serious consequences, such as hypertension and renal function impairment. Renal artery stents are widely used in clinical practice as important therapeutic tools for excluding aneurysms, maintaining patency, preventing rupture, and maintaining renal function [226,227]. The development of renal vascular stents has evolved through several generations. The first generation of renal vascular stents, such as Palmaz®, which was the most broadly used renal vascular stent in early period. Normal blood flow is restored by dilating the blood vessels via placement inside the narrowed renal arteries [228-230]. However, due to design flaws, the use of this type of stent can lead to complications such as thrombosis, postprocedural restenosis, and stent migration. Subsequently, second-generation renal vascular stents, such as Express® and Precise®, have emerged. These stents have improved in design and material selection, with better pressure adaptation and elasticity, allowing for better adaptation to the morphology of the renal vessels [231]. However, there is still some risk of restenosis, and long-term follow-up and monitoring are needed. To further minimize risks such as restenosis, third-generation renal vascular stents, such as RadiusTM stent, have further improved in design to increase placement precision and maneuverability, reducing the risk of postprocedural restenosis [232]. However, there is still some risk of complications, such as vascular injury and thrombosis. The Absolute ProTM and BeGraft® Peripheral devices, which are more commonly used in clinical settings today, have more advanced designs and materials. Moreover, these devices provide better vessel deployment and reconstruction results and simultaneously reduce the risk of complications such as thrombosis and restenosis [233,234].
In retrospect, the design and materials of renal artery stents have improved significantly over the past decades. Future stent design will focus more on flexibility and adaptability to cope with complex and tortuous renal artery anatomy, improve therapeutic efficacy and minimize complications, thus improving patient health. It is believed that future scientific research and technological innovation will continue to promote the progress and development of renal artery stent therapy.
5.4
Venous stents
With the continuous improvement in material science and medicine, novel materials have been explored for use in venous stents. The introduction of materials such as titanium alloys, nickel-titanium alloys, and stainless steel has greatly improved the corrosion resistance and mechanical strength of venous stents [235]. These innovative materials provide better biocompatibility and long-term durability to stents while reducing the risk of thrombosis. For example, the Vici venous stent utilizes a stainless steel stent with excellent mechanical strength and durability; however, the risk of postprocedural restenosis remains a concern [236,237]. In addition to material innovations, the design of venous stents continues to improve, with sinus venous stents being specifically designed for the treatment of intracranial venous sinuses; however, the incidence of postprocedural thrombosis and restenosis requires further study. To prevent restenosis, the Zilver Vena Venous Stent utilizes drug encapsulation technology, which allows for the slow release of drugs by coating the surface of the stent or encapsulating the drug in the stent material, further reducing the incidence of restenosis.
The future development of stents will continue to focus on improving the adaptability, long-term effects, and safety of stents; addressing problems such as restenosis with the help of new materials and design techniques; and enhancing individualized treatment to meet patients' disease characteristics and needs [238].
5.5
Aortic stents
The success of coronary stenting in the 1980s stimulated interest in the potential of vascular stents in the treatment of aortic disease. The first generation of stents was introduced in the early 1990s. These devices are usually made of stainless steel or cobalt-chromium alloys, and the stents are implanted in areas of aortic stenosis or occlusion through balloon dilatation [238]. It results in good dilatation and revascularization; however, fiber overgrowth and endothelialized calcification may increase the risk of thrombosis and restenosis [239,240]. To overcome the shortcomings of first-generation stents, new materials and designs have been started for second-generation stents. For example, the Jostens GraftMaster Stent Graft for aortic aneurysm treatment combines a stent and a prosthetic vessel to provide excellent tightness and durability, but the complexity of the procedure and the accompanying risk of vessel rupture, which requires precise surgical skills, force it to be withdrawn from the market [241,242]. In recent years, the emergence of third-generation stents has led to the further development of aortic stents. Third-generation stents are manufactured with biodegradable materials, such as polymers or biological derivatives, that are capable of being absorbed by the body within an appropriate time frame [243]. This biodegradable stent reduces the implant retention time and decreases the risk of complications. Moreover, third-generation stents have good biocompatibility and release drugs, resulting in precise treatment of specific aortic lesions [244-248].
Future developments will continue to focus on improving stent design, biodegradable materials, and stent implantation techniques to improve surgical outcomes and patient quality of life. New stents will focus on mitigating problems such as thrombosis, restenosis, and leakage while optimizing stent fit and durability. Individualized treatment will also become increasingly important, with the most appropriate stent and surgical plan selected based on the patient's specific needs and lesion characteristics.
Research progress on cerebrovascular stents, renal artery stents, peripheral stents, venous stents, aortic stents and other vascular stents are shown in Table S2 (Supporting information) [108,115,129,216,246-263].
6.
Conclusions and perspectives
Although vascular stents provide an alternative option to treat vascular disorders in a minimally invasive method, they have the possibility of causing certain complications after implantation, such as thrombosis, inflammation, restenosis, vascular injury, displacement and endoleakage. Hence, it is essential to develop innovative vascular stents to reduce or prevent complications. Conventional vascular stents provide mechanical support for expanding or occluding vascular lesions and thus treating lesions and making vessels patent. Furthermore, functional vascular stents provide mechanical support and innovative efficacy to achieve better mechanical manifestations, safer biocompatibility and faster vascular repair. To better simulate the in vivo microenvironment, strategies such as drug-eluting design, biodegradable materials and tissue-engineered constructions have been developed to achieve better performance.
Future development trends for vascular stents are expected to prioritize their performance, biocompatibility, and clinical accessibility. More research focusing on vascular repair after vascular stent implantation is needed to provide a better understanding of the tissue reactions of vascular stents. The selection of materials aimed at yielding biodegradable vascular stents should be tailored for vascular repair with enhanced biocompatibility and mechanical properties. The design of vascular stents may be transformed or improved to better fulfill the rehabilitation requirements of patients with vascular disease. For instance, for the endovascular treatment of aortic dissection, a novel design strategy in which a bare stent is used to expand the false lumen combined with an occluder to occlude the entry tear may effectively prevent the drawbacks of conventional covered aortic stents. Furthermore, a novel design in which a vascular graft is integrated with a covered stent may be beneficial for shortening the operation duration for patients with DeBakey type A aortic dissection. Moreover, tissue-engineered constructions that integrate clinical medicine, biology and engineering technology may contribute to faster and better repair of vascular diseases. Finally, additional potential application scenarios, such as BCIs through the jugular vein to the superior sagittal sinus to treat paralysis, may be explored to broaden the application of vascular stents in the future.
Overall, future exploration of vascular stents may concentrate on establishing novel design strategies based on a new comprehensive understanding of vascular diseases as well as tissue reactions after stent implantation. Furthermore, more researches are needed to determine how to enhance the mechanical properties of biodegradable vascular stents. Finally, various application scenarios may be used to treat vascular or even nonvascular diseases via endovascular stenting access.
Declaration of competing interest
The authors declare that they have no known competing financial interests or personal relationships that could have appeared to influence the work reported in this paper.
This work was supported by Natural Science Foundation of China (No. 31930067); Natural Science Foundation of Sichuan Province (No. 23NSFSC5880); Chengdu Medical Research Project (No. 2022004); Natural Science Foundation of Clinical Medical College and Affiliated Hospital of Chengdu University (No. Y202206); Postdoctoral Research and Development Fund of West China Hospital, Sichuan University (No. 2023HXBH052).
Supplementary materials
Supplementary material associated with this article can be found, in the online version, at doi:10.1016/j.cclet.2024.110492.
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Figure 1
The application of stent implantation in various vascular diseases across different parts of the body. It covers common vascular conditions such as cerebral artery, carotid artery, renal artery, coronary artery, aorta, lower limb arteries, and venous obstructions, highlighting the critical role of stents in treating these areas. This review systematically elucidates, for the first time, the clinical applications of stents in improving blood flow and preventing complications, providing a comprehensive reference for the widespread use of vascular stents.
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