The Promus Premier Drug-Eluting Coronary Stent System

Prepared by:

The Tovally Men:

Billy Chen

Max Cornell

Todd Goodall

Aymen Maktari

Shiva Mehta

Students: University of Michigan, Engineering 100: Section 102

Project Due Date:

April 24, 2014

Prepared for:

Dr. George T. WynarskyInstructor, Materials Science and Engineering,

University of Michigan

Dr. Elizabeth HildingerInstructor, Program in Technical Communication,

University of Michigan

Table of Contents

Foreword…………………………………………………………………………………………1

Summary…………………………………………………………………………………………1

Introduction………………………………………………………………………………….......3

Anatomy and Physiology………………………………………………………………………...3The Heart………………………………………………………………………………….3 The Coronary Arteries…………………………………………………………………….3 Interior of an Artery....…………………………………………………………………….4

Coronary Artery Disease………………………………………………………………………...4Risk Factors……………………………………………………………………………….4

Health Effects…………………………………………………………………………........5

The History of Treatments for Coronary Artery Disease……………………………………..5 Coronary Artery Bypass Grafting…………………………………………………………5

Balloon Angioplasty…………………………………...………………...………….……..6Coronary Stents and Drug-Eluting Coronary Stents…………………………..………….6

Form of the Promus Premier Drug-Eluting Coronary Stent……………………………….…7

Function of the Promus Premier Drug-Eluting Coronary Stent……………………………...8

Material Properties…………………………………………………………………….………...9

Alternative Treatments………………………………………………………………..……….10Minimally Invasive Direct CABG…………………………………….………………….10Bioabsorbable Stents…………………………………………………………………….10

Limitations of Stenting…………………………………………………………………………11 Stent Recoil………………………………………………………………………………11Late Stent Thrombosis……………………………………………...……………………11Restenosis………………………………………………………………………………..11Uneven Polymer Degradation…………………………………………………………...12

Current Research and Development in Drug-Eluting Coronary Stent Technology……….12Nonpolymeric Stents……………………………………………………………………..12 Endothelial Progenitor Cell Capture Stents……………………………………………..13

Design Recommendation……………………………………………………………..………...13

References……………………………………………………………………………………….15

ForewordYou asked our team to write a report about a biomedical device of our choice. We requested to study the drug-eluting coronary stent, and you granted our request. We decided to research the Promus Premier drug-eluting coronary stent system. We researched the anatomy of the heart and coronary arteries, coronary artery disease, the history of treatment for coronary artery disease, and the form and function of the Promus Premier. We also researched the material properties of the Promus Premier, the alternative treatments for coronary artery disease, the limitations of drug-eluting coronary stents, and current research and development in the field of drug-eluting coronary stents. Finally, we formulated a design recommendation for the Promus Premier based upon our research. The purpose of this document is to provide you with a comprehensive and organized collection of our findings and design recommendation.

SummaryCoronary artery disease, or CAD, is the buildup of plaque in the arteries of the heart. Plaque is a waxy substance that consists of cholesterol and cellular waste. The plaque obstructs the flow of oxygen-rich blood to the heart muscle. This obstruction can lead to a heart attack. The insertion of a coronary stent is a common treatment for coronary artery disease.

The heart is composed of four chambers. Blood flows through all four chambers as the heart beats. The heart pumps blood into the coronary arteries and to the rest of the body. The coronary arteries supply the heart with oxygen-rich blood. The muscle of the heart must receive a constant supply of oxygen so that it is able to pump blood throughout the body.

Coronary artery disease can cause serious health problems. Some risk factors of coronary artery disease include high blood cholesterol, high blood pressure, unhealthy diet, old age, lack of exercise, and family history of CAD. Symptoms of CAD include chest pain, shortness of breath, rapid heartbeat, and nausea. Many patients experience few or no symptoms until they have a heart attack. Most commonly, heart attacks are caused by blood clots that form in a narrowed artery. These clots completely obstruct the flow of blood to the heart muscle. This deprivation of oxygen-rich blood to the heart muscle may be fatal.

The treatment of CAD has evolved over the past 50 years. Initially, CAD was treated by grafting a blood vessel around the afflicted coronary artery to bypass the blockage. A less invasive method called balloon angioplasty was then developed. In balloon angioplasty, the surgeon inserts and inflates a balloon in the obstructed artery, compressing the plaque. Coronary stents are now used in addition to balloon angioplasty. Coronary stents are small cylindrical mesh structures that remain in the artery to keep plaque compressed even after the balloon is removed. Drug-eluting coronary stents have become prevalent over the last twelve years. They are coated with a drug that is released into the artery in order to prevent clots from forming near the stent.

Boston Scientific developed the Promus Premier Drug-Eluting Stent in 2013. It is a cylindrical metal mesh that is coated with a polymer containing an immunosuppressive drug. The stent is strong enough to withstand the pressures that result from blood pumping through the artery and is flexible enough to expand to fit against the walls of the artery.

Stents are inserted in a process called coronary angioplasty. A collapsed stent is inserted with a balloon into the obstructed coronary artery. The balloon is inflated and the stent is pushed against the walls of the artery. The balloon is removed and the stent stays in place. Sometimes the stent causes scar tissue to form near it. If enough scar tissue forms, the artery can become blocked again. The drug that coats the Promus Premier and other drug-eluting coronary stents prevents the formation of scar tissue. The drug may release over days, weeks, or months depending on the model of stent.

The Promus Premier is made of a platinum chromium alloy. The alloy is composed mainly of iron, platinum, and chromium. Platinum chromium is strong enough and stiff enough to withstand the stresses applied to the stent by the arterial walls. The material also has excellent corrosion resistance and good biocompatibility. The metal platform of the stent is coated with a complex thermoplastic polymer. The polymer degrades in the body, releasing the drug. As it degrades, it does not adversely affect the body.

Stents are not the only treatment for coronary artery disease. Recently, a minimally invasive method of coronary artery bypass grafting has been developed. Another alternative to the use of traditional stents is the use of bioabsorbable stents. Bioabsorbable stents are similar to traditional stents; however the artery gradually absorbs bioabsorbable stents. Bioabsorbable stents can be made of metals or polymers that do not harm the body as they are absorbed.

Even though stents are a popular treatment for coronary artery disease, they have some limitations. Stent recoil occurs when the stent partially returns to its collapsed state after implantation. Stent recoil can occur if the pressure from the arterial walls is too great. Late stent thrombosis occurs when an unnecessary blood clot forms in the artery near the site of the stent. The clot blocks blood flow through the artery, possibly causing a heart attack. Restenosis is the formation of scar tissue around the stent. The scar tissue partially blocks blood flow and increases the risk of a heart attack. Another limitation of modern stents is uneven polymer degradation. There is no way to ensure that the polymer coating on the stent degrades and releases the drug evenly.

Currently there is research being done to curb these limitations. One development involves coating the metallic platform of non-polymeric stents with the drug. The metal gradually releases the drug from its micropores. This eliminates the problem of uneven polymer degradation. Endothelial progenitor cell (EPC) capture stents are also being developed. The stents are covered in an antibody coating that attracts nearby EPCs, which facilitate the natural healing process of the artery and minimize other problems after stent implantation.

To address some of the limitations of the Promus Premier, we have developed a design recommendation. We believe that a combination of a non-polymeric and EPC capture stent technology will be most effective in addressing the aforementioned limitations. We also propose a change in the metallic platform used. We recommend the use of 316L stainless steel, as it has a microporous structure that allows for direct application of the drug and the antibody coating. As a result, our recommended stent is much more biocompatible than the Promus Premier.

IntroductionThe drug-eluting coronary stent is an artery-sized cylindrical implant that treats coronary artery disease by restoring blood flow to the coronary arteries. Coronary artery disease is prevalent in the United States, with about 600,000 people dying of the disease every year (Centers of Disease Control and Prevention, 2013). This report will discuss the anatomy of the heart and coronary arteries, coronary artery disease, the history of treatment for coronary artery disease, and the form and function of a specific drug-eluting coronary stent, the Promus Premier Everolimus-Eluting Coronary Stent System. This report also details the material properties of the Promus Premier, the alternative treatments for coronary artery disease, the limitations of drug-eluting coronary stents, and current research and development in the field of drug-eluting coronary stents as well as our design recommendation for the Promus Premier.

Anatomy and PhysiologyWhen discussing the necessity for drug-eluting coronary stents, the relevant system of the body is the circulatory system. At the center of the circulatory system is the heart. The function of the heart is to pump blood through arteries and veins in order to deliver oxygen-rich blood to all of the parts of the body.

The HeartAs shown in Figure 1, the heart is composed of four chambers. Each of these chambers helps to pump blood through the body. During one heartbeat, the heart goes through the cardiac cycle. Initially, deoxygenated blood flows into the right atrium, and then into the right ventricle. Next, blood leaves the heart through the pulmonary arteries and travels to the lungs, where it picks up oxygen. The oxygenated blood returns to the heart, flows into the left atrium, to the left ventricle, and then leaves through the aorta. The aorta branches off and leads to all of the arteries in the body, including the coronary arteries (Anatomy of the Heart, 2009).

The Coronary ArteriesThe coronary arteries deliver oxygen-rich blood to the heart muscle. If the muscle is deprived of the necessary amount of oxygen, it can die. Dead muscle is unable to pump oxygen-rich blood to the body. As Figure 2 shows, the aorta branches off to the left and right sides of the heart. These two main branches are called the left and right coronary arteries. The main coronary artery behind the heart is called the posterior coronary artery. The main coronary arteries branch off to smaller arteries. Coronary arteries are unique because they deliver

Figure 2. Coronary arteries. (Adapted from Heart Bypass - The Problem.)

Figure 1. The human heart. (Adapted from Heart diagram, 2013.)

oxygen-rich blood to the heart, but they are very similar in structure to other arteries of the body (Anatomy of the Heart, 2009).

Interior of an ArteryArteries are made up of three layers, as shown in Figure 3. The outer wall of an artery is made up of semi-rigid collagen fibers that provide structure for the cylindrical shape. The inner lining is very thin and very smooth so blood can flow through the artery with almost no friction. A layer of smooth muscle lies between the exterior wall and the inner lining. The muscle contracts to help push blood through the artery (Artery Cut Section, 2014).

Coronary Artery Disease Coronary artery disease (CAD) is the narrowing of the coronary arteries due to atherosclerosis, the buildup of plaque in the arterial walls (University of Maryland Medical Center, 2012). Plaque is a waxy substance that consists of cholesterol and cellular waste. It lies between the inner lining and smooth muscle of the arterial wall, and develops with a fatty core and thin fibrous cap (American Heart Association, 2012).

Atherosclerosis begins with cholesterol, an essential fat that comes from the liver and animal products. It also may originate from cholesterol transport proteins (University of Maryland Medical Center, 2012). These are known as lipoproteins. Lipoproteins are categorized by size: low-density lipoproteins, the “bad cholesterol,” and high-density lipoproteins, the “good cholesterol.” Low-density lipoprotein cholesterol circulating through the bloodstream tends to deposit in the arterial walls (WebMD, 2012). These cholesterol deposits, in addition to cellular waste, constitute plaque. As plaque builds up, normal bodily processes such as oxidation (the release of unstable particles known as oxygen-free radicals) and inflammation (a protective mechanism against harmful stimuli) harden the plaque and narrow the arteries. This narrowing results in a deprivation of oxygen-rich blood to the heart muscles (University of Maryland Medical Center, 2012). Figure 4 compares a normal artery to a narrowed artery. As shown, a normal artery does not restrict the flow of oxygen-rich blood, whereas a narrowed artery leads to restricted blood flow.

Risk Factors Risk factors of CAD include high blood cholesterol level, high blood pressure, unhealthy diet, diabetes, smoking, high alcohol consumption, and old age. Other risk factors are lack of exercise,

Figure 3. Cross sectional view of an artery. (Adapted from Artery Cut Section, 2014.)

Figure 4. Cross sections of a normal coronary artery and an artery narrowed by plaque. (Adapted from American Heart Association, 2012.)

Figure 6. Results of CABG. (Adapted from Healthwise Inc.)

obesity, family history of CAD, race, and depression (University of Maryland Medical Center, 2012).

Health Effects The primary symptom of CAD is angina, chest pain as a result of a deprivation of oxygen to the heart muscle. Angina has two main states: stable angina and unstable angina. Stable angina is predictable chest pain and is triggered by any event that increases oxygen demand such as exercise and emotional tension. Unstable angina is less predictable and is indicative of a more severe condition. Other common symptoms include shortness of breath, rapid heartbeat, and nausea. Some patients with CAD experience few or no symptoms until they have a heart attack (University of Maryland Medical Center, 2012).

The end result of atherosclerosis is a heart attack. Commonly, a heart attack occurs as a result of rupturing or tearing of the fibrous cap covering the plaque. Tiny blood cells called platelets stick to the site of the rupture and form a blood clot (University of Rochester Medical Center). The left portion of Figure 5 shows how the blood clot blocks the passage of oxygen-rich blood to the heart, causing a heart attack. In rare cases, a heart attack results from a severe case of atherosclerosis (University of Maryland Medical Center, 2012). The right portion of Figure 5 shows how severe plaque buildup can lead to a completely blocked artery. As a result, oxygen-deprived heart muscles die, causing a heart attack (University of Maryland Medical Center, 2012).

The History of Treatments for Coronary Artery DiseaseThe blockage of arteries due to plaque buildup was a problem that needed to be treated. As a result, doctors and engineers have been developing methods that restore regular blood flow. A variety of treatment options have been developed in the past 50 years beginning with surgery.

Coronary Artery Bypass GraftingThe first successful coronary artery bypass grafting (CABG) was performed in 1964 by Russian cardiologist Vasilii Kolessov. Kolessov used the internal mammary artery to successfully restore proper circulation throughout the body of patients with blocked arteries (Mack, 2003). This technique was improved over time. Modern CABG involves grafting a blood vessel to bypass the blockage (University of Michigan Health System, 2013). Figure 6 shows the results of CABG.

The success of this procedure made it the most common type of open-heart surgery

Figure 5. Rupture of the fibrous cap and clot formation (left). Severe plaque buildup (right). (Adapted from Healthwise, 2012.)

in the United States and a popular treatment option for people suffering from severe blockage of their coronary arteries (University of Michigan Health System, 2013). Despite its success, CABG’s invasive nature was not suitable for all who suffered from CAD due to a high level of blood loss during the operation. As a result, less invasive techniques were developed.

Balloon AngioplastyPhysician Andreas Gruentzig developed balloon angioplasty in 1977 (Emory Healthcare, 2014). This less invasive technique involves the use of a balloon catheter. The balloon catheter is guided to the site of the blockage in the coronary arteries. As shown in Figure 7, it is then inflated in order to compress the plaque inside the artery and increase the diameter of the artery to increase blood flow (National Heart Lung and Blood Institute). The less invasive nature of balloon angioplasty was also successful; however, it does not permanently widen the arteries. Over time, the arteries narrow again and blood flow decreases.

Coronary Stents and Drug-Eluting Coronary StentsThe shortcomings of the balloon angioplasty treatment led to the use of coronary stents as a way to maintain the structure of the widened artery. Julio Palmaz developed this technique in 1989 (Ruygrok & Serruys, 1996). The first coronary stents were made of metal mesh and were placed in the arteries through a procedure similar to balloon angioplasty known as coronary angioplasty.

The use of coronary stents reduces the re-narrowing of the arteries after the procedure but it does not prevent re-narrowing. As a result, researchers developed the drug-eluting coronary stent. The first drug-eluting coronary stent was the Cypher by Cordis Corporation in 2003 (Biosensors International). Soon numerous drug-eluting coronary stents were in production.

Boston Scientific developed the Promus Premier Everolimus-Eluting Platinum Chromium Coronary Stent System in 2013. It is structurally strong and it efficiently delivers a drug called Everolimus.

Form of the Promus Premier Drug-Eluting Coronary StentThe Promus Premier is a cylindrical metal mesh coated with a polymer containing an immunosuppressive drug. The cylindrical shape allows the stent to fit tightly to the walls of the artery when it is inserted. The

Figure 8. Geometry of Promus Premier. (Adapted from Boston Scientific.)

Figure 7. Insertion of balloon catheter (left). Expansion of balloon (center). Results of balloon angioplasty (right). (Adapted from Healthwise Inc.)

Figure 11. Path of catheter insertion. (Adapted from Mayfield Clinic & Ringer.)

cylinder is composed of sinusoidal rings linked by branches as shown in Figure 8. Due to its geometry, the Promus Premier is able to expand from a collapsed state as Figure 9 shows. When it is collapsed, the diameter is 2.25 mm and the length is 8 mm. When the stent is expanded, its diameter increases to 4 mm and its length increases to 38 mm (PR Newswire, 2013).

The materials used to create stents are chosen with three primary criteria in mind: strength, flexibility, and visibility (Boston Scientific, 2014). The alloy must be strong enough to endure the pressures created by the blood pumping through the arteries. The alloy needs to be flexible so that it may supplement the flexibility of the geometry of the stent. It also needs to be highly visible so that it may be maneuvered effectively and it may be seen in the event of future operations (Boston Scientific, 2014). The Promus Premier is made of a platinum chromium alloy. The alloy satisfies all of the criteria listed above (Boston Scientific, 2014).

The drug used for the stent may vary depending on the model. The Promus Premier is coated with a thermoplastic polymer called PVDF-HFP loaded with Everolimus, as shown in Figure 10 (Boston Scientific, 2014 and Sigma-Aldrich, 2014). Everolimus suppresses the immune system near the stent’s location. This stops some of the problems associated with non-drug-eluting coronary stents.

Function of the Promus Premier Drug-Eluting Coronary StentAs previously discussed, drug-eluting coronary stents are implanted in a procedure called coronary angioplasty. During coronary angioplasty a doctor slides a thin tube called a catheter that holds a small balloon through a small cut in the femoral artery as shown in Figure 11. The doctor then maneuvers the catheter through the aorta and into the afflicted artery. Once the catheter has reached the blocked section of the artery, the doctor inflates the small balloon to open up the artery. The force of the balloon pushes against the walls of the artery. This force compresses the plaque and widens the artery to increase blood flow. The catheter is then removed (The Society for Vascular Surgery, 2012).

Next, the doctor inserts the stent into the widened artery. In order to place the stent inside the artery, it is collapsed and fitted on a different catheter with a deflated balloon inside of it, as shown in Figure 12. The doctor inserts this catheter the same way as the first one and maneuvers the stent to the now-widened artery. Once the stent is in place, the doctor inflates

Figure 9. Collapsed stent (left) vs. expanded stent (right). (Adapted from Covidien.)

Figure 10. Stent strut cross section.

the balloon inside of the stent, opening the stent and pushing it against the walls of the artery as shown in Figure 12. When the stent has been forced into place, the balloon is deflated and the catheter is removed (The Society for Vascular Surgery, 2012). Figure 12 shows the stent left in place.

The stent now has an integral role in maintaining the health of the patient’s artery. The force of the stent against the walls of the artery keeps the artery clear of blockage. As a result, blood flows more easily through the afflicted passageway. Over time, the walls of the artery grow over the stent.

Sometimes the stent may cause scar tissue to form near it. If enough scar tissue forms, the artery can be blocked again (The Society for Vascular Surgery, 2012). To combat this problem, the drug that coats the stent slows the development of scar tissue by preventing platelets from sticking together near the stent. As previously mentioned, the Promus Premier is coated with Everolimus (Boston Scientific, 2014). The immune system suppression caused by Everolimus keeps the stent safe and effective while the arterial walls grow over it. The drug may release over days, weeks, or months depending on the model of stent (American Heart Association).

Material Properties The Promus Premier is composed of two materials: platinum chromium alloy and PVDF-HFP. The properties of the platinum chromium alloy are shown in Table 1.

Table 1: Platinum Chromium Alloy PropertiesPlatinum chromium alloy is composed primarily of iron, platinum, and chromium (O’Brien, et al., 2010). The high yield strength of the alloy allows the Promus Premier to have thinner struts than other stents (US National Library of Medicine National Institutes of Health, 2010). As shown by its high elastic modulus, platinum chromium is stiff enough to minimize elastic deformation once it has been expanded. Platinum chromium also has good biocompatibility due to its excellent corrosion resistance. These two properties make the alloy generally safe to use in

Figure 12. Collapsed stent (top). Expanding stent (center). Expanded stent (bottom). (Adapted from British Heart Foundation.)

(O’Brien, et al., 2010)

coronary arteries. Platinum chromium’s ductility makes it ideal for being shaped into the struts that comprise the structure of the Promus Premier.

Table 2: PVDF-HFP Properties

The Promus Premier also consists of a layer of polymer called polyvinylidene fluoride-co-hexafluoropropylene (PVDF-HFP) (Medical Materials Database 2010). The properties of the polymer are shown in Table 2. The layer of PVDF-HFP rests on top of the metal mesh alloy. As shown in the table, the elastic modulus of PVDF-HFP is very low. This low modulus causes PVDF-HFP to expand with very little force. The low tensile strength does not diminish the effectiveness of the polymer as the polymer simply needs to contain the drug. Plastic deformation of PVDF-HFP is not a problem. PVDF-HFP degrades over a period of 6 months in the body. This degradation period is ideal for a consistent and timely release of the drug contained inside the polymer. The biocompatibility of the polymer indicates that the polymer does not produce any negative effects while breaking down in the body.

Alternative TreatmentsWhile drug-eluting coronary stents are an effective treatment for CAD, there are other treatments available to patients.

Minimally Invasive Direct CABGA popular alternative to the use of coronary stents is coronary artery bypass grafting (CABG). As mentioned earlier, CABG was the earliest treatment for CAD. The shortcomings of the procedure in the past were its invasive nature and the high-blood loss during the surgery. The treatment is still used today, but with major improvements.

Over the past few decades, advances in technology have led to several changes including a variation known as minimally invasive direct coronary artery bypass grafting (MIDCABG). MIDCABG is different in that it does not require the opening of the chest bones. Instead incisions are made between the ribs to access only the blocked artery. This less invasive procedure reduces the loss of blood during treatment. Due to such advances and success in treating CAD, CABG is the most common heart surgery in the United States (National Heart, Lung, and Blood Institute, 2012).

Bioabsorbable Coronary Stents The use of bioabsorbable coronary stents is an alternative to the use of drug-eluting coronary stents. Bioabsorbable coronary stents are composed of either a polymer or a metal with a polymer coating (Qi, Yang, Maitz, & Huang, 2013). The advantage of bioabsorbable stents is

(Su & Miao, 2014 and Boston Scientific, 2014)

that after a certain period of time, the artery absorbs the stent. This absorption reduces the formation of scar tissue and the risk of restenosis.

Bioabsorbable stents can be polymer-based or metal-based. One example of a polymer-based stent is the ReZolve2 stent by Reva Medical. This stent is composed of a tyrosine polycarbonate that was engineered to degrade over time. Figure 13 shows the polymeric bioabsorbable stent. As the stent degrades, it also elutes Sirolimus to prevent restenosis. The stent completely degrades in about 36 months (Qi et al., 2013). Biotronik manufactures another bioabsorbable stent model called DREAMS (Drug-Eluting Absorbable Metal Scaffold). These stents are composed of magnesium and trace amounts of rare earth metals (Qi et al., 2013). These stents contain a bioabsorbable metal coated in a drug-eluting polymer. DREAMS degrades in four months after implantation (Qi et al., 2013).

Limitations of StentingThe use of coronary stents is a very effective treatment for coronary artery disease. However, stents are not a perfect solution to the problem. There are several problems that can occur with stents after implantation. Stent recoil is a short term problem. Late stent thrombosis, restenosis, and uneven polymer degradation are long term problems.

Stent Recoil Stent recoil occurs when a stent returns to its collapsed state after implantation. When stents are implanted they are inflated to a diameter that is larger than that of the artery. When the balloon is deflated, the arterial wall puts pressure on the stent and pushes it inward. Figure 14 shows a cross-sectional view of an artery containing a stent undergoing recoil. Usually the stent is partially collapsed so that it is the size of the natural artery. Occasionally, the artery puts too much pressure on the stent and the stent can collapse completely. Stent recoil occurs immediately after implantation of the stent (Aziz, Morris, Perry, & Stables, 2007).

Late Stent Thrombosis Late stent thrombosis is a long term problem associated with stenting. As shown in Figure 15, thrombosis is the formation of a blood clot inside an artery. Thrombosis

Figure 13. Bioabsorbable stent. (Adapted from Reva Medical, Inc.)

Figure 14. Stent recoil.

Figure 15. Late stent thrombosis.

is likely to occur around the stent because the stent is a foreign object within the artery. The clot can partially or completely block the flow of blood through the artery, possibly causing a heart attack (Pfisterer, 2008).

RestenosisRestenosis is a problem that involves the gradual buildup of scar tissue in the artery. The immune system can respond to the stent in an adverse manner, as the blood cells do during thrombosis. The immune system causes scar tissue to form around the stent. Figure 16 is a cross sectional view of scar tissue overgrowth in an artery. The scar tissue partially blocks the flow of blood through the artery. Drugs in drug-eluting coronary stents are designed to suppress the immune system and prevent the formation of scar tissue. However, the drugs do not always function as they are intended (Dangas & Kuepper, 2002). Uneven Polymer DegradationThe drug release mechanism in drug-eluting stents can occur unevenly. The polymer coating on the metal platform is designed to degrade slowly and evenly. As the polymer degrades, the drug is gradually released into the artery. However, if the polymer degrades unevenly, the drug is less likely to be able to prevent restenosis. Figure 17 is a cross sectional view of a stent strut that has experienced uneven polymer degradation (Ma, Wu, & Robich, 2012).

Current Research and Development in Drug-Eluting Coronary Stent TechnologyScientists and engineers are constantly trying to improve the design and functionality of drug-eluting coronary stents. The ideal stent has several properties: high flexibility to enable delivery through the cardiovascular system, high radial strength to undergo minimal recoiling, low toxicity, bioactive nature, and consistent drug delivery. Optimization of the drug-eluting coronary stent focuses on preparing new platforms, drugs, and methods of drug delivery. The primary focus is on the methods of drug delivery, as these influence not only drug dosage, but also the interactions between the stent and the human body (Qi et al., 2013).

Figure 16. Restenosis.

Figure 17. Cross-section of a stent strut with uneven polymer degradation.

Nonpolymeric StentsCurrently, scientists are trying to develop drug-eluting coronary stents with polymer-free drug delivery systems, as the presence of a drug-loading polymer coating has proven to result in late stent thrombosis. One such method of polymer-free drug delivery involves spraying the drug on a bare metal stent with a microporous surface, as seen in Figure 18. The microporous surface acts as a reservoir, allowing for a slow release of drugs. After complete drug elution, the remaining microporous surface structure of the stent promotes adhesion and migration of endothelial cells. The endothelial cells facilitate arterial healing (Qi et al., 2013).

Endothelial Progenitor Cell Capture StentsAnother innovation in drug-eluting coronary stent research is the development of the endothelial progenitor cell (EPC) capture stent. As shown in Figure 19, the EPC capture stent has immobilized antibodies on the stent strut surface, along with the drug-loaded polymer coating of a traditional drug-eluting stent. These antibodies target EPC surface antigens to attract and capture nearby EPCs. EPCs help accelerate natural arterial healing, lowering the risk of restenosis and stent thrombosis (Qi et al., 2013).

Design RecommendationIn order to address many of the problems associated with the Promus Premier, two designs of drug-eluting coronary stents that are currently being developed should be combined. The Promus

Figure 18. Cross sectional view of a non-polymeric stent strut (left). Enlarged view of the stent's microporous surface (right).

Figure 19. Cross-sectional view of an EPC capture stent (left). EPC capture mechanism (right).

Figure 20. A stent strut cross-section of a non-polymeric EPC capture stent.

Premier should become a non-polymeric EPC capture stent. Figure 20 shows a cross-section of a strut of the redesigned stent. In this stent, the metallic platform is made from 316L stainless steel – a metal often used in drug-eluting coronary stents. The structure of this steel has micropores that allow the drug to rest in it (Qi, et al., 2013). A layer of antibodies covers the metallic platform.

Table 3: Material Comparison

Table 3 compares several properties of platinum chromium and 316L stainless steel. Platinum chromium is the alloy currently used as a platform for the Promus Premier and we have recommended 316L stainless steel as a substitute. The materials are similar with two notable exceptions. First, the yield strength of 316L stainless steel is significantly lower than the yield strength of platinum chromium. Second, the biocompatibility of the 316L stainless steel with the antibody coating is an improvement over the biocompatibility of the platinum chromium.

Our recommendation has numerous advantages that make it an improvement over the current model of the Promus Premier. The antibody coating lowers the risk of late stent thrombosis and restenosis while accelerating the natural healing response of the artery. The non-polymeric structure removes the problem of uneven polymer degradation. The lower yield strength of the 316L stainless steel lowers the stent’s resistance to opening during coronary angioplasty. These advantages decrease the risk that further procedures will be necessary to maintain the patient’s health. The only notable cost associated with our design is that it will require thicker struts due to the lower yield strength of 316L stainless steel. This change causes little concern, however, since many stent platforms are made from 316L stainless steel. As a result the redesigned stent will have similar strut thickness to many other drug-eluting coronary stents.

(AZoM, 2014 and O’Brien, et al., 2010)

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