Since the dawn of the stent development in 1986, where utilization of bare-metal stents (BMS) was the successful possibility. But as the modern technologies re-imagined these devices continuously by applying new materials, developing stent coatings based on inorganic and organic compounds including drugs, nanoparticles, or biological components such as genes and cells, as well as adapting stent designs with different fabrication technologies. However, long-term complication, such as in-stent restenosis, late thrombosis, local chronic inflammation, and re-occlusion rates occurring due to stent implantations. Which requires further development of stent devices and deep analysis of their long-term stability and failure mechanisms to control antagonistic effects.
Critical factors like optimization of mechanical, physical-chemical, and biological stent properties are to be optimized. Especially the biological aspects related to the adhesion of salts, proteins, cells, and microorganisms on the stent surface causing undesired effects like encrustation, biofilm formation, inflammation, and stent failure.
Several classes of materials have been tested as potential coatings for stent manufacturing. The stent surfaces can be modified by using oxides and nitrides of metals. Chemical surface modification can also be assured by molecular layer deposition, silanization technology utilizing commercially available silanes (ethyltrietoxysilane, octyltriethoxysilane) rich in diverse functional groups helping to achieve the desired stent properties. Organic Coatings using polymer materials can be used with and without drug elution, with different success rates.
The main problem of biodegradable and non-biodegradable polymer layers lies in their degradation products, arising as a result of contact with biological fluids and the ability to trigger inflammation followed by thrombosis formation. Bio-Based Coatings are special stent coatings based on biological materials, aim to proliferate, differentiate, release growth, and, finally, inhibit thrombosis and neointimal hyperplasia. There are a lot of inorganic materials such as oxides, nitrides, silicide and carbide, noble metals, hydroxyapatite-based materials, diamonds which potentially capable of improving the properties of the implant surface.
Metals that can fabricate biodegradable stents having sufficient mechanical characteristics and appropriate biocompatibility are Magnesium (Mg), iron (Fe), and zinc (Zn). Despite multiple advantages of Mg as bioresorbable stent material the major hurdle is its application consists in too fast and inhomogeneous degradation in the physiological milieu. Another problem of Mg application in stent manufacturing is related to the release of hydrogen as a result of the degradation process leading to inflammation and systemic toxicity. Zn Stents is proposed as a new biomaterial for use in bioresorbable cardiovascular stents. It shows sufficient mechanical and biological characteristics required for optimal stent performance. Zinc and its alloys show the appropriate rate of degradation for stent application. In human physiology, zinc is a crucial oligo element playing important catalytic, structural, and regulatory roles within the cells.
Biodegradable polymeric materials show great promise in different medical applications allowing local delivery of biologically active agents and drugs. PLLA proved to be highly biocompatible, Polymeric biodegradable stents still demonstrate pure mechanical properties disturbing their application in patients. The clinical studies of everolimus-eluting PLLA stent Absorb-BVS-System (Bioresorbable vascular scaffold; Chicago, IL, USA) have shown its safety with good mechanical support during the first 3 months of implantation. In comparison, Bioresorbable Metal has advantages over Polymer Stents.
Drug, Nanoparticle, and Gene-Eluting Stents
Drug-eluting stents are stents with drug-eluting functions, being realized by means of an anti-inflammatory/antithrombotic drug-containing polymer coating or direct immobilization of drugs on the stent surface. Since the first approved DES, CYPHERTM in 2003, different stents have been developed to ensure quick endothelialization, the low proliferation of Smooth Muscle Cells (SCMs) and to avoid late in-stent restenosis. In the second generation, the development of zotarolimus- and everolimus-eluting stents have further reduced that risk exhibiting lower hypersensitivity, high flexibility, acceptable recoil, and better compliance. The third generation of DES belongs to the bioresorbable drug-eluting vascular scaffolds (BVS), which disappear or degrade completely after a certain time in the vessel.
Furthermore, stents can be improved by using DNA, siRNA, and miRNA of drugs. The achievement of optimal drug release kinetics and drug loading capacity are the most important challenges for DES. Burst drug release (elution of 90% of the drug amount within two days) in various PF-DES have been reported repeatedly. As a result, the desirable inhibition of neointima proliferation cannot be reached. ES mostly uses polymer coatings to incorporate pharmacologic agents. These are non-biodegradable polymers, such as phosphorylcholine, C10, C19, and polyvinyl pyrrolidone (PVP, BioLinx polymer system), parylene C.
The controlled drug delivery mechanisms can be classified as either physical or chemical mechanisms or their combination. Physical mechanisms include diffusion of drug molecules through a polymer layer, dissolution, or degradation of polymer matrix controlling the drug release rate, use of osmotic pressure for drug release, and use of ion exchange for ionized drugs. The chemical mechanisms, however, are based on breaking covalent bonds that connect drug molecules to a delivery vehicle, such as polymer chains, by either chemical or enzymatic degradation. Physical mechanisms have an advantage over chemical ones as they allow for controlling the drug release kinetics by the drug delivery system itself. Furthermore, there is no need to chemically modify the drug molecules, such as in chemical mechanisms.
Mechanical Aspects of Stents
Material (elastic (Young’s) modulus (YM), yield strength (YS), ultimate tensile strength (UTS), and elongation) define the characteristics of the stent (radial strength, acute and chronic recoil, axial and radial flexibility, deliverability, profile, and lifetime integrity). Various, influential, sometimes conflicting factors affect one or more of these characteristics: materials, manufacturing methods, the general shape of the stent/stent design and size, struts shape, size, and number. Materials are responsible for corrosion resistance, biocompatibility, radio-opacity, and—along with manufacturing methods. Open and closed cell design: the general shape of the stent (coil, tubular mesh, slotted tube) and bridging between rings (peak-to-peak, peak-to-valley, and mid-strut-to-mid-strut connections) can influence flexibility, radial strength, and scaffolding (ability to support tissue; thus, preventing prolapse).
Most stents available on the market have struts oriented along the longitudinal axis. Some of them, such as Taxus Liberté, have those oriented at an angle relative to the stent longitudinal axis (multi-angled struts). In future studies, it should be examined if using angled struts and some of the above-described measures can help to achieve a more homogeneous distribution of mechanical loadings, resulting in the better reliability of stents as medical devices.
Cardiovascular diseases are multiplying worldwide, a promising approach of stent technology, researchers and clinicians are paying great attention to developing new materials, methods, and solutions in order to enhance the clinical outcome of currently existing stent types, aiming at more safety for patients, and a higher success rate of treatments. Different technologies of stent fabrication, especially related to coated, bioresorbable, as well as drug-eluting stents have been considered. Despite the huge progress in the stent technology, no ideal stent exists until now. It is expected that some of the existing problems will be overcome in the close future, as we can especially remark in the numerous patents filled in the last few years.