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Globally, approximately 20 of deaths are attributable to cardiovascular disease. Advances in the field of stents have revolutionized the treatment of coronary artery diseases. To provide effective treatment for coronary artery disease, a stent has to be deliverable and flexible, causes minimal trauma to the vessel wall, cause minimal inflammatory reaction, endothelialize well, provide scaffolding for the vessel and finally promote vessel healing and remodelling. Bare-metal stents (BMS) introduced in 1994 have been used as most common treatment for symptomatic coronary artery disease, but long-term results have shown problems of in-stent restenosis (ISR) and stent thrombosis. Intense work to overcome the above problems has successfully led to the introduction of drug-eluting stents (DES) in 2002. Despite the success of DES uncertainty still remains on overall safety. Today, in the search for improving the performance of available DES various developments and clinical studies are ongoing to increase the long-term safety and efficacy of stents. Present available DES has significantly reduced the rate of restenosis; it has reduced morbidity, mortality and economic costs associated with the percutaneous treatment of coronary artery disease. Patients no longer have to come back for cardiac catheterizations due to ISR. The success of present DES has shifted the focus on further developments toward enhancing long term safety and efficacy of these devices using Bioabsorbable systems.
The coronary arteries supply a constant flow of oxygen-rich blood to the heart. If plaque builds up in these coronary arteries, blockages can develop, reducing blood flow to the heart leading to coronary artery disease (CAD). Currently, over 16 million Americans have CAD. Consequently, almost eight million Americans have suffered a myocardial infarction (MI). One method of treating CAD and MI is the implantation of an expandable stent within a compromised artery (for example, one partially occluded by atherosclerotic plaque). In 2007 alone, approximately 560,000 Americans received a coronary stent implantation . Cardiovascular procedures performed in the United States have increased to more than triple in last decade. This increased trend is expected to continue with the aging of the population, coupled with epidemics of obesity and diabetes mellitus .
Percutaneous transluminal coronary angioplasty (PTCA) and bypass surgery are well established methods for treating CAD. PTCA alone was inadequate, and this leads to development of bare-metal stents (BMS), with significantly improving long term results . BMS is a small, tubular, wire-mesh device which is pre-loaded in a collapsed form onto a catheter balloon, threaded to the narrowed section of the artery and expanded within the vessel. Once expanded, the BMS acts as a mechanical scaffold, reducing elastic recoil and maintaining post-treatment vessel patency. BMS generally result in extremely favourable initial clinical results, however re-narrowing of the treated artery is commonly observed in 20-30% of patients. This re-narrowing of the treated artery is due to in-stent restenosis (ISR). It is mainly due to excessive neointimal proliferation within the stented segment [5-7].
To deal with this ISR, a repeat procedure of angiography needs to be performed and despite extensive research, no therapy consistently prevents this difficult problem. Systemic drug delivery fails to prevent restenosis; therefore local administration of pharmacologic agents directly to the site of injured arterial tissue was prescribed. The immobilization of pharmacological agents on the stent surface and their sustained release from the surfaces is a very promising approach to prevent post angioplasty ISR . Clinical evaluation has overwhelmingly proven the superiority of DES for the reduction of ISR rates compared to BMS, even in complicated situations . In patients presenting with acute myocardial infarction, treatment with DES is associated with decreased 2 year mortality rates and a reduction in the need for repeat revascularization procedures as compared to treatment with BMS . Kirtane et al. performed safety and efficacy study for DES and BMS as a comprehensive meta-analysis of randomized trials and observational studies, and reported that the use of DES was associated with reduced death and myocardial infarction. Moreover, the unrestricted use of DES compared with BMS did not appear to be associated with adverse safety outcomes and was associated with a significant reduction in repeat revascularization of the treated vessel . Research in this area is currently centred on the development and evaluation of new improved DES which maintain the impressive clinical benefits while eradicating long-term safety concerns, which might be experienced with currently approved devices .
2. Design of drug-eluting stents
BMS were introduced in 1994, thereafter, in an effort to address ISR problem associated with BMS, intense work on stent development has successfully led to the introduction of DES in 2002. Since arrival, DES has transformed the practice of interventional cardiology by drastically reducing ISR and the need for repeat revascularization.
Intense work on stent development has successfully led to the introduction of diverse DES (Figure 1). First generation DES, such as sirolimus eluting (Cypher) and paclitaxel eluting stents (Taxus) have improved results of coronary intervention by improving early results and reducing the risk of restenosis. But, there is presently debate on the safety of first generations DES regarding late stent thrombosis, especially after discontinuation of dual antiplatelet therapy. Thus, second generation DES such as zotarolimus eluting (Endeavor) and everolimus eluting (Xience V) stents have been introduced with promising anti-restenotic efficacy as well as long-term safety. They differ from the first generation stents with respect to the antiproliferative agent, the polymer layer and the stent frame [12-16].
Mani et al. thoroughly reviewed (1) different materials used for stents preparation, (2) surface characteristics that influence stent-biology interactions and (3) the use of polymers in different stents, especially those that are commercially available. They reported that every material has its own pros and cons. It is not be possible for a single material to posses all the desired requirements . Ako et al. reported design criteria for the ideal DES with respect to 3 complementary perspectives: deliverability, efficacy, and safety. Deliverability includes flexible material, design, thin strut thickness, small device profile and self expanding nature. Efficacy includes uniform drug delivery, required radial force/less recoil, lesion-specific stent configuration and disease specific application. Safety includes biodegradable stent, bio mimicking coating, biodegradable coating and cell specific drug action . DES normally consists of three components: (a) a stent platform, (b) stent coating and (c) a therapeutic agent.
2.1. The stent platform
Stent design affects both immediate and long-term clinical outcome. During implantation, stents are crimped to a balloon-tipped catheter and introduced to the cardiovascular system via the femoral or radial arteries, although this procedure has clear disadvantages  but still in use. Stent must have a low crimped profile and must possess a high level of flexibility to enable delivery through the tortuous cardiovascular system. During expansion stent should experience minimum shortening and upon deployment it should be conform to the vessel geometry without any unnaturally straightening of the vessel. Additionally, stent should provide optimum vessel coverage and possess high radial strength to undergo minimal radial recoiling. Modular or slotted-tube configurations are most suitable and are employed for manufacturing stents [5, 20].
The serious procedural complications associated with failures of stent deployment in target lesions include vessel injury, dissection and thrombosis. Pathological studies have implicated delayed arterial healing and poor re-endothelialization after stent implantation. Stents are manufactured typically from biologically inert metals such as stainless steel. In recent years, however metallic alloys such as cobalt-chromium have proved superiority over steel as the material of choice for stent design. Self-expanding DES often use nitinol (nickel-titanium) as the platform material. These metallic alloys have been developed with increased levels of strength and X-ray attenuation, allowing stents to be designed with significantly thinner struts and are more biologically inert. The identification of long-term safety issues with the first generation DES has also increased clinical interest in the development of stents that are more biologically based, including fully biodegradable stents and stents using biomimetic and biodegradable polymers [5, 18, 21].
2.2. The stent coating
PTCA cannot be performed without damaging blood vessels and eliciting restenosis. Drug elution at the target site is a clear solution to this problem. As a result, most of currently approved DES consists of a metallic scaffold surrounded by polymer matrix containing drug. These polymers bind the drug to the stent and modulate the elution of the drug to the arterial tissue. Some adverse reactions may be caused by these polymers. Thus, biocompatibility of the polymers used for coating stents is very vital. For effective suppression of intimal growth, the ideal DES polymer should be non-thrombotic, non-inflammatory, non-toxic to cells and should encourage arterial healing by re-endothelialization. Stent surface should be haemocompatible to avoid thrombo-embolic processes until the re-endothelialization process is finished. For this comparative study examining a polymeric stent coating affecting the haemocompatibility of a stainless steel stent was performed and better haemocompatibility of the polymer-coated stents was evident .
In addition, DES must be capable of being stretched without flaking or delaminating. The insufflation of the balloon during implantation leads to a cracking of the polymer coating party with delamination. This is shown for first generation stents . Secondly, the polymer needs to be able to deliver the drug at a sustained, controlled and predictable rate . Parker et al. recently summarizes the key requirements for polymers used in the DES, including physical properties, stability, compatibility with drugs, biocompatibility with vascular tissue and control of drug release .
Manufacturing methodologies of DES are based mainly on mechanical processes, which tend to generate coatings that have poor stability, with potential hazards. Surface characteristics of a stent material, including surface energy, surface texture, surface potential, and the stability of the surface oxide layer influence thrombosis and neointimal hyperplasia . Levy et al. studied and described coating irregularities like delaminating, cracking, and peeling in commercially available stents. Quantitative in vitro durability tests for DES, referred to as Quantified Defects (QD) were implemented on various stent polymer-coated models to determine ability to differentiate between coatings. Stents coating defects were tested using light microscopy, scanning electron microscopy and a micro-balance. DES tested demonstrated a deteriorating durability profile as reflected by QD indices. Different coating models showed unique QD indices that reflected their superior or inferior coating durability. These results indicated that the described methodologies were able to differentiate between different models [24, 26, 27].
Polymers used for coating stents can be broadly classified into (a) biostable/durable (non-biodegrable) polymers e.g. polyethylene-co-vinyl acetate, poly-n-butyl methacrylate, poly(styrene-b-isobutylene-b-styrene), polyurethane, silicone, polyethylene terepthalate etc. (b) biodegradable polymers e.g. polyglycolic or polylactic acid or their copolymers etc. and (c) biological polymers e.g. phosphorylcholine, hyaluronic acid and fibrin [17, 28].
The most successful method of facilitating drug adhesion and delivery from a stent involved the use of permanent synthetic polymer coating materials such as polyethylene-co-vinyl acetate, poly-n-butyl methacrylate, and the tri-block copolymer poly(styrene-b-isobutylene-b-styrene) (Table 1). First generation DES were coated with these biostable permanent polymer to provide controlled release of the anti-restenotic drug . Subsequently, these permanent polymers have been substituted by advanced biocompatible permanent polymers such as phosphorylcholine and the copolymers (Table 1). These advanced polymers mimic the phospholipids on the outer surfaces of red blood cells, resulting in minimal thrombus formation upon deployment with minimal adverse clinical effect on late healing of the vessel wall . Recently, new generation of DES is being developed using bioabsorbable polymers (Table 2) which degrade over time [25, 30].
Between BMS and DES, there are stents in the market coated with different materials (without drug) which suppress platelet adhesion, so called passive-coated stents. Main aim of these coatings is to provide a biologically inert barrier between the stent surfaces; circulating blood and endothelial wall. Variety of different stent coatings have been evaluated including diamond-like carbon, different polymers, silicon-carbide, titanium-nitride-oxide (TiNO) etc. Pilgrim et al. compared the efficacy of passive stent coating containing TiNO with DES (releasing zotarolimus). But, passive stent coating with TiNO was found inferior to DES in reducing restenosis .
Table 1 Different generations of DES
First generation DES
polyethylene-co-vinyl acetate and poly-n-butyl methacrylate
Soft elastomeric polymer- poly(styrene-b-isobutylene-b-styrene)
Second generation DES
[5, 32, 33]
Persistent, Biolinx polymer, blend of 3 polymers: hydrophobic C10, hydrophilic C19 and polyvinyl pyrrolidone
[5, 25, 34]
Persistent, nonerodible, two polymers (a) Polyvinylidene fluoride co-hexafluoropropylene and (b) poly-n-butyl methacrylate
Third generation DES
ION Stent (Boston Scientific)
Local delivery of drugs using DES provides both biological and mechanical solution and has emerged as a very promising approach effective in management of ISR. For local drug delivery to be successful, challenges to be addressed include (1) decision on the most appropriate agent to be use, (2) determination of the proportion of the systemic dose needed locally and (3) identification of a biocompatible vehicle that can deliver drug for the required therapeutic window [39, 40].
Common component of cancer chemotherapy, paclitaxel reduces neointimal hyperplasia after balloon and stent mediated injury
Polymerisation of the Î±- and Î²-units of tubulin, thereby stabilizing microtubules which are needed for G2 transition into M-phase
Macrocyclic antibiotic with potent immunosuppressive properties inhibits several phases of the restenosis cascade, such as inflammation, neointimal hyperplasia formation, total protein and collagen synthesis
Pro-drug that binds to specific cytosolic proteins (FK-506 binding protein-12), which blocks the cell proliferation
Zotarolimus and Everolimus
Zotarolimus and everolimus are analogues of Rapamycin with higher n-octanol/water partition coefficients which favours a slow release from the stents, lipophilic character favours crossing cell membranes to inhibit neointimal proliferation of target tissue
They bind to cytosolic FK-506 binding protein-12 and inhibit the proliferation of smooth muscle cells and T-cells.
[21, 43, 45].
Tacrolimus is less potent than sirolimus for inhibiting vascular smooth muscle cell proliferation or migration with less antiproliferative effects on endothelial cell compared with sirolimus. But, with its potent anti-inflammatory effects, tacrolimus may represent a promising compound for the use in DES
Immunosuppressive agent that also binds to cytosolic FK-506 binding protein-12. The resulting complex interacts and inhibits calcineurin and in this way inhibits the T-lymphocite signal transduction and IL-2 transcription
Semi-synthetic sirolimus analogue with an alkoxy-alkyl group replacing hydrogen at position 42-O.Â
Biolimus possesses enhanced anti-inflammatory and antiproliferative activity with an improved pharmacokinetic profile.
At a cellular level, biolimus forms a complex with intracellularÂ FK-506 binding protein-12, which binds to the mammalian target ofÂ rapamycinÂ and reversibly inhibitsÂ cell-cycleÂ transition of proliferatingÂ smooth muscle cellsÂ with a similar potency toÂ sirolimus
Actinomycin D affects the "S" phase of the cell cycle by forming a stable complex with double-stranded deoxyribonucleic acid inhibiting ribonucleic acid synthesis and is a powerful inhibitor of cell proliferation
Actinomycin D is also a cellular proliferation inhibitor,
Dexamethason and more general the corticosteroids are well established anti-inflammatory drugs, used systemically for a broad range of inflammatory diseases and inhibiting proliferation of fibroblasts, smooth muscle cells and macrophages Preclinical data and limited observations in humans using DES for local drug delivery have suggested beneficial effects of dexamethason on neointimal proliferation
Restenosis after stent implantation is mainly characterized by an inflammatory response to the procedural injury and an intense fibrocellular response including smooth muscle cell proliferation
thus reducing thrombus formation, improving blood flow and arterial potency and inhibiting cyclic blood flow variation, enhances endothelialization and may potentially be an effective therapeutic alternative to improve currently available DES
antiplatelet GP IIb/IIIa antibody, antihuman-CD34 antibody
[43, 50, 51]
Four classes of drugs (anti-inflammatory, antithrombogenic, antiproliferative and immunosuppressive) are candidate drugs to be used in DES. These drugs inhibit one or more biochemical pathways leading to restenosis. Some research is also conducted using antibodies blocking specific receptors as active compounds. Several reports have been published evaluating these drugs regarding their release kinetics, effective dosage, safety in clinical practice and benefit .
3. Drug release from stents
Release kinetics and applied dose plays a major role in the duration and magnitude of arterial drug uptake, equally important is the mechanism by which the drug is released. Success of stent based drug delivery system is empirically associated with effective delivery of potent therapeutics to the target site at a therapeutic concentration, for a sufficient time and in a biologically active form. [53-55].
Phosphate buffered saline with pH 7.4 at 37Â°C is most commonly employed as a medium to monitor the in vitro release kinetics of DES. But in case of sirolimus eluting stent, this medium is found to be inappropriate since sirolimus hydrolyses to form newer compounds with opened lactam ring at alkaline pH and buffer salts . Neubert et al. developed a novel in vitro dissolution test for DES based on the compendial flow through cell. The model contains a compartment simulating the vessel wall enabling the examination of drug release and distribution. These findings emphasize the necessity to adapt dissolution testing for DES to the unique conditions influencing delivery to the vessel wall to learn more about local distribution and to anticipate the in vivo performance of DES .
Seidlitz, reported vessel simulating flow through cell to examine the release from DES in vitro. Furthermore, the in vitro release and distribution examined experimentally were modelled mathematically using finite element (FE) methods. The vessel simulating flow through cell with FE modelling represents a unique method to analyse drug release and distribution from DES . Mcginty et al. described family of mathematical models to describe the elution of drug from polymer coated stents into the arterial wall. These models include the polymer layer, the media, the adventitia, a possible topcoat polymer layer and atherosclerotic plaque. Importance of transmural convection, diffusion and drug-dependent parameters in drug delivery and deposition were also investigated. Furthermore, the effect on cellular drug concentrations with altered drug release rate from the stent was also investigated .
Pan et al. studied the different drug-eluting controlled biodegradable polymer coatings fabricated on stainless steel stents and reported that depending on the drug type, different DES exhibited different drug release profile. There were two basic release profiles, two-phase release profiles with burst release or linear release profile without any burst release . Mikkonen et al. investigated the drug elution properties of novel drug-eluting bioabsorbable stents in vitro with four different drugs: dexamethasone, indomethacin, simvastatin and ciprofloxacin. These drugs were hydrophobic to different degrees. It was also observed that both the concentration and the hydrophilicity of the drug had a great influence on the drug elution profile with different speeds of elution .
4. Safety and efficacy of DES
Significant evolution in catheter-based technologies for percutaneous coronary intervention has occurred since the introduction of coronary balloon angioplasty by Andreas Gruntzig in 1977. Later, balloon angioplasty was supported by BMS and subsequently DES. With this progress, randomized comparative clinical trials have demonstrated a progressive decline in both angiographic and clinical restenosis. DES has revolutionized cardiovascular treatment by virtually eliminating ISR. But following widespread clinical use of DES, multiple safety issues have been identified raising issues such as late state thrombosis and increased mortality [24, 61]; Table 3 shows safety concerns with DES.
Controversies regarding the safety and efficacy of DES persists, and therefore like all other therapies, DES should be chosen selectively and correctly . Nordmann et al. evaluated the effect of drug eluting vs. BMS for the treatment of coronary artery disease on overall, cardiac and non-cardiac mortalities. Preliminary evidence suggests that sirolimus eluting stents may lead to increased non-cardiac mortality .
Stent thrombosis is a potentially fatal adverse event that often leads to myocardial infarction and/or death. The exact cause of stent thrombosis is not yet fully understood a number of patient, lesion, and procedural factors have been associated with an increased risk of stent thrombosis . It was emerged that restrictive and non-uniform definitions of stent thrombosis had been utilised during the initial clinical evaluation of the first generation DES. Thus, the "Academic Research Consortium" subsequently recommended standardised definitions of stent thrombosis and in 2007 these definitions were adopted . First generation DES were widely adopted by interventional cardiologists with up to 90% of stent procedures carried out in the US by late 2005 . Durable polymers in first generation DES have been linked to local inflammatory reaction leading to a positive vessel remodelling, late incomplete stent apposition and in some cases, stent thrombosis . Therefore, one of important factor of uncertainty about the efficacy of DES is the use of polymers. It is not certain whether the used polymers are stable and inert over a longer period of time. Curcio et al. reported methacrylate coating induces vascular smooth muscle cell apoptosis. This apoptotic property of methacrylate coating should be taken into account in the evaluation [42, 67]. In another study, the healing and inflammatory responses of polymer free BMS, polymer free sirolimus eluting stents and polymer free sirolimus eluting stents plus Estradiol to Cypher has been compared. It has been shown that the non-erodible polymer coatings employed by DES (particularly the first generation Cypher and Taxus) impair stent strut endothelialisation and may induce late hypersensitivity reactions and subsequent stent thrombosis [14, 68].
Stent infection is another rare outcome of coronary stent implantation, although, clinical experience with regard to the diagnosis and management of coronary artery stent infection remains limited. Schoenkerman and Lundstrom reported 3 cases of coronary stent infections; 2 with mycotic aneurysms that ruptured into an adjacent cardiac chamber, and one with purulent pericarditis .
As for concern for efficacy associated with DES, in Sweden, 47,967 patients were evaluated who received a coronary stent and were entered into the "Swedish Coronary Angiography and Angioplasty Registry" between 2003 and 2006. In the primary analysis, patients who received one DES (10,294 patients) with those who received one BMS (18,659), after adjustment for differences in clinical characteristics of the patients and characteristics of the vessels and lesions were compared. Results suggested there was no overall difference between the group that received DES and the group that received BMS in the combined end point of death or myocardial infarction. The average rate of restenosis during the first year was 3.0 events per 100 patient-years with DES versus 4.7 with BMS. Among high-risk patients, the adjusted risk of restenosis was 74% lower with DES than with BMS. As compared with BMS, DES is associated with a similar long-term incidence of death or myocardial infarction and provides a clinically important decrease in the rate of restenosis among high-risk patients .
5. Future of Drug eluting stents
DES is considered better in the treatment of symptomatic coronary artery disease. Following widespread clinical use of these DES, multiple safety issues have been identified in late follow-up that have prompted efforts toward development of bioresorbable polymers, polymer-free metal platforms, as well as completely resorbable DES platforms. The ultimate goal of these efforts is to provide safe and durable coronary patency. Currently, the next generation (newer) DES has being developed, which involves optimize the three major components of DES: the stent platform, the polymer coating and the drug. New technologies developed/under development includes mainly use of polymer free DES and use of biodegradable polymers and stents etc. .
5.1. Polymer-free DES
Since the continuous presence of a durable polymer in the coronary vasculature is believed to be associated with impaired vascular healing and a moderate increase of life-threatening late or very late stent thrombosis, thus substantial efforts are currently underway to identify alternatives to biostable polymeric coating . The use of polymer-free stents may have a potential long term benefit over traditional polymeric coated DES. Steigerwald et al. reported assessment of two novel Rapamycin-eluting stent coating technologies using probucol and blended by shellac to abstain use of a durable polymer . Prunotto et al. evaluated acute and chronic tissue response to a polymer-free drug-eluting stent implantation in a porcine coronary artery model. In this, the drug is hosted in troughs created on the external surface of stent struts therefore eliminating the need for carrying polymers . Table 4 showed few polymer-free DES.
Tada et al. evaluated local delivery of Biolimus A9, from a polymer-free BioFreedom stent. BioFreedom stents were associated with reduced neointimal proliferation as compared to polymer coated sirolimus-eluting Cypher stent (SES). The polymer-free Biolimus A9 coated stent demonstrates equivalent early and superior late reduction of intimal proliferation compared with SES in a porcine model. After implantation of BioFreedom stent, delayed arterial healing was minimal, and there was no increased inflammation at 180 days compared with SES implantation . Costa et al. assess the safety and efficacy of the novel VESTAsync-eluting stent combining a stainless steel platform with a nanothin-microporous hydroxyapatite surface coating impregnated with a polymer-free low dose of sirolimus. The novel VESTAsync-eluting stent was effective in reducing lumen loss and neointimal hyperplasia at 4 and 9 months, with no evidence of late catch-up by quantitative coronary angiography or intravascular ultrasound .
Levi et al. reported a new crystallization methodology involved temperature induced crystallization process for Rapamycin to crystallize and adhere on to metallic surfaces like stents. This carrier free DES coating minimizes the use of synthetic substances. These coatings displayed stability and biocompatibility. Coating obtained from this process allows drug release gradually over a period of a several weeks. Additionally, the controllability of crystallization process enables the generation of a variety of morphologies, physical states and thickness coating. This process may be implemented further using various drugs and other supersaturated systems .
5.2. Bioabsorbable Drug Eluting Stent
Despite all the benefits of the using a metallic DES, their limitations have generated interest towards biodegradable technology. The realization about the probability of DES polymers causing the inflammatory reactions led to the development of Bioabsorbable polymer based DES. Bioabsorbable DES is a device that could achieve excellent acute and long-term results, but itself get disappear completely within months, thereby avoiding the need for prolonged dual antiplatelet therapy. These biodegradable stents, which are made of polymers or metal alloys with or without a drug coating, have the potential to scaffold the artery to allow natural healing to take place, and then biodegrade. Such stents would obviate the need for long-term antiplatelet therapy. Since no foreign material would be left behind, future surgical options will not be limited and follow-up with non-invasive imaging such as CT angiography would be possible [8, 77]. Several biodegradable stents have entered into clinical trials, with many more at the preclinical stage of development . Table 5 showed few bioabsorbable DES.
Table 5 Polymer-free Drug eluting stent and Bioabsorbable Drug eluting stents
VESTAsync (MIV Therapeutics)
Nanoporous hydroxyapitate Effective in reducing lumen loss and neointimal with no evidence of late catch-up
Microporous surface Antirestenotic effect that is not inferior to that observed with the polymer-based paclitaxel-eluting stent
Biotronik stent (Biotronik)
Absorbable metal stent 93% magnesium and 7% rare earth metals, zig-zag helical coil design
Degrades into inorganic salts, not release an antiproliferative drug to counter the intimal hyperplastic response to stenting
Poly- L -lactic acid
The deployment of the stent was rather complex, requiring thermal balloon expansion to actuate the device
BVS stent (Abbot Vascular)
Poly-L-lactic acid, Cohort A: out-of-phase sinusoidal hoops with straight and direct links; cohort B: in-phase hoops with straight links
Coating of poly-D,L-lactic acid that contains and controls the release of the antiproliferative agent everolimus, 80% release in 30 days
The REVA (REVA MEDICAL, INC.)
Polymertyrosine-derived polycarbonate polymer, slide and lock (ratchet) design
The absorption time can be modified
Bioabsorbable Therapeutics Stent (Bioabsorbable Therapeutics Inc.)
Polymer salicylate+adipic acid linker molecules, Tube with lasercut voids
Polymer backbone that gives the stent the physical structure and a polymer coating that contains and controls the release of the antiproliferative agent
Two broad categories of materials are generally used: those made from organic biopolymers and those made from corrodible metals. However, to date, none of the materials/stents tested have been able to establish a perfect balance between biocompatibility, the kinetics of degradation needed to maintain mechanical strength to limit recoil, and inflammation . In the late 1990s, a bioabsorbable (Igaki-Tamai) stent, made of a high-molecular-weight poly-L-lactic acid (PLLA), was implanted in 15 patients (25 stents) to evaluate the feasibility, safety, and efficacy of the PLLA stent. No major cardiac event, except for repeat angioplasty, developed within 6 months. Coronary PLLA biodegradable stents are feasible, safe, and effective in humans. Long-term follow-up with more patients required to validate the long-term efficacy of PLLA stents  . Ormiston et al. reported 1-year follow-up of patients with a single coronary-artery lesion who had received a biodegradable polymer-based stent that elutes the antiproliferative drug everolimus. The novelty of the study is use of a superficial everolimus-eluting polymer layer, which led to nearly complete elimination of both intimal hyperplasia and the need for reintervention. This study shows the feasibility of implantation of the bioabsorbable everolimus-eluting stent, with an acceptable in-stent late loss, minimal intrastent neointimal hyperplasia, and a low stent area obstruction .
Everolimus eluting poly-L-lactide stent, which demonstrated comparable restenotic rates with BMS and a low incidence of major adverse cardiac events, suggest that there has been significant progress with respect to the earlier prototypes [84, 85]. The acute recoil observed could potentially be addressed with the polytyrosine REVA stent which incorporates a novel locking mechanism within its design [80, 84]. Compared with biodegradable polymers, there are fewer metals used in the manufacture of biodegradable stents. The only metal biodegradable stents in trials is the Biotronik absorbable magnesium stent. Unlike magnesium stents, there has been little progress with iron stents, which remain in the pre-clinical phase, and this may be partly due to the longer degradation times needed and potential issues related with iron clearance [80, 81].