Development of next generation biodegradable drug-eluting coronary artery stents

Abstract

Cardiovascular diseases are a leading cause of mortality globally, causing approximately 17 million deaths annually. Additionally, this number is predicted to rise to 23 million by 2030. The most common type of cardiovascular disease is coronary heart disease, a disease of coronary arteries that supply oxygen rich blood to the heart. Coronary artery disease is the build-up of a waxy substance called a plaque inside the coronary artery which leads to its narrowing and blockage. In current medical practice, coronary heart disease is commonly treated through balloon angioplasty and stenting to open the artery. Current stents are drug- eluting, metallic, and permanent, and recipients require prolonged anti-platelet therapy. Permanent stenting is not required. The diseased vessel can heal within 6 months to 1 year after intervention. As such, the concept of biodegradable stents has emerged as the alternative to conventional stenting, in which the stent degrades away leaving behind only the healed vessel. The first generation of biodegradable stents has been linked to higher rates of late stage thrombosis, and it has been suggested that this is due to increased strut thicknesses that cause disturbance to the laminar blood flow and result in activation of thrombogenic pathways. The aim of this thesis is to develop customizable, biodegradable, multi drug eluting coronary artery stents by using polymer chemistry, materials science, and additive manufacturing. The novel materials developed in this work are to be blood-compatible, biodegradable, have sufficient mechanical properties, promote endothelialisation, have multi-drug eluting properties, and be processable through additive manufacturing techniques. To achieve this, we used the following approaches: (1) Design and additive manufacturing of custom-made biodegradable nanocomposite based coronary artery stents (2) Design and synthesis of biocompatible and biodegradable core-cross linked star-brush polymers for antithrombotic drugs (3) Development of multi-drug eluting biodegradable nanocomposite-star polymer materials for application as coronary artery stents utilizing additive manufacturing.