**4. Drug-Eluting Stent (DES)**

**1. Introduction**

416 Muscle Cell and Tissue

disease [3].

steps:

**3. What causes restenosis?**

renarrowing of the vessel.

Atherosclerosis is a disease in which a plaque builds up inside your arteries. The plaque builds up of fat, cholesterol, calcium, and other substances found in the blood. Over time, plaque hardens and narrows your arteries [1]. Arteries are blood vessels that carry oxygen-rich blood to organs in the body, and this plaque limits the flow of oxygen-rich blood to organs and other parts of body. Thus, atherosclerosis can lead to serious problems, including heart attack, stroke, or even death. Percutaneous transluminal coronary angioplasty (PTCA) is a technique used to

At the beginning, the doctor moves a guiding catheter into the artery with the blockage. Once the guiding catheter is in right place, a guide wire is moved across the blockage site and then a balloon catheter is moved to the blockage site. The balloon is inflated for a few seconds to compress the blockage against the artery wall and then the balloon is deflated. This proceeding can be repeated for a few times. Each time the balloon is pumped, the plaque widens a little more and enables the blood to flow through. If it is needed, a stent is placed within the coronary artery to keep the vessel open. Following this, the catheter is removed and the procedure is completed, as seen in Figure 1. As a result, the narrowed artery is enlarged by PTCA. PTCA is sometimes called coronary angioplasty. Coronary angioplasty has become increasingly popular as a result of its low morbidity and mortality and reduced hospital stay in comparison with surgery. Coronary angioplasty is generally effective and safe, but restenosis is frequent, occurring in about 30-40% of cases [2]. Restenosis limits the long-term beneficial effects of PTCA and related procedures. PTCA may be defined as the initial gain in artery lumen size, and restenosis can be defined as the loss of gain. Prevention of restenosis after successful PTCA remains one of the most challenging issues in the obstructive treatment of coronary artery

As we mentioned above, stent placement is another option that is applied during angioplasty. Stent is a metallic scaffold that keeps the narrowed coronary artery portion open. Besides, as a metallic scaffold, the body may also perceive as alien. In fact, the trauma created by angio‐ plasty and stenting in tissue is more effective on restenosis. The trauma created by angioplasty and stenting leads cell stimulations in tissue, triggers cells in that region, and causes cell proliferation, migration, and thrombosis. Finally, cell movement and thrombosis lead to the

Restenosis following balloon dilation of the vascular endothelium is thought to occur in three

widen the narrowing in a coronary artery without surgery.

**2. What happens during angioplasty?**

Early difficulties with coronary stents included a risk of early thrombosis (clotting) resulting in occlusion of the stent. Coating stainless steel stents with some other materials such as platinum or gold were evaluated. However, this approach by itself did not eliminate the problem. Then researchers coated stent surface with biocompatible polymers; moreover, the idea of using these polymers as drug reservoir is generated. Scientists developed drug-eluting stents and used the devices themselves as a tool for delivering medication directly to the arterial wall. The medication is entrapped in polymer layers or loaded into polymeric nano‐ particles, and nanoparticles are embedded in polymeric layers. A drug-eluting stent consists of three main parts.

The first part is the metallic scaffold. The metallic scaffold may be constituted by using different types of metallic materials such as stainless steel, nitinol, cobalt, chromium, platinum, gold, magnesium alloy, etc.

The second part is the drug-eluting polymer-coated inner surface of the scaffold. The polymercoated inner surface of the scaffold is generally used as a drug carrier, which holds and elutes the drug in a controlled manner. The polymers used for DES is generally biodegradable polymers like polylactic acid (PLA), polyglycolic acid (PLGA), and polycaprolactone (PCL). Besides, nonbiodegradable polymers like polybutylmethacrylate (PBMA), polymethylmetha‐ crylate (PMMA), phosphorylcholine, and polyethylene terphthalate (PET) are also evaluated. The third part is the medication that is released from stent directly to arterial wall. Drugs used in DES are immunosuppressive and antiproliferative drugs like sirolimus, everolimus, zotarolimus, paclitaxel, etc., to inhibit neointimal growth, which would cause restenosis [2].

Although the drug-eluting stents significantly reduced the rate of restenosis, it did not completely eliminate restenosis, especially in complex lesions. Additionally, delayed endo‐ thelialization after drug-eluting stent implantation is considered to be the cause of late thrombosis. Therefore, scientists have suggested that gene transfer can be an option to address these problems by inhibiting proliferation of vascular smooth muscle cells (VSMCs) and by promoting endothelialization with some genes [6]. Then scientists used stents as a tool to deliver growth factors, plasmids, and antisense oligonucleotides directly to arterial wall. Several studies have been carried out for the delivery and controlled release of genes encoding antiproliferative proteins, miRNAs, peptide structures, and siRNAs to the target tissues through different polymeric materials.
