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Chapter 1
Introduction
1.1 Cardiovascular disease
Heart disease is the leading cause of death and disability in both industrialised nations and the developing world, accounting for approximately 40% of all human mortality [1]. Prognosis is poor with 40% mortality within 12 months of diagnosis, and a 10% annual mortality rate thereafter [2]. The economic burden imposed by this disease has reached more than $33 billion in the US and more than £700 million in the UK annually [3].
Heart failure is a condition reflecting impairment of the pumping efficiency of the heart, and it is caused by a variety of underlying diseases, including ischemic heart disease with or without an episode of acute myocardial infarction, hypertensive heart disease, valvular heart disease, and primary myocardial disease. The single most common cause of left-sided cardiac failure is ischemic heart disease (also called coronary artery disease) with an episode of acute myocardial infarction. Myocardial infarction typically results in myocyte slippage. The weakening of the collagen
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extracellular matrix results in heart wall thinning and ventricular dilation. The impairment of the heart wall muscle is permanent because, after a massive cell loss due to infarction, the myocardial tissue lacks significant intrinsic regenerative capability to replace the lost cells [4]. The enlargement in ventricular volume leads to progressive structural and functional changes in ventricles (called ventricular remodelling) [4]. Ventricular remodelling is initially compensatory, but adds further inefficiency to the mechanical pumping of the ventricular muscle, predisposing towards the end stage of congestive heart failure (CHF) (or just heart failure) [4], a condition in which the heart cannot pump a sufficient amount of blood to the meet the metabolic requirements of the body .
Interventional therapy, such as surgery or implantation of pacing devices to control electrical/mechanical asynchrony, are now receiving more widespread application, in particular for patients with marked symptoms and marked limitation in activity [5], [6], [7], [8], [9] and [10]. However, both drug and interventional therapies cannot adequately control disease progression to the end stage [11]. Eventually, heart transplantation is the ultimate treatment option to end-stage heart failure. Owing to
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the lack of organ donors and complications associated with immune suppressive treatments, however, scientists and surgeons constantly look for new strategies to repair the injured heart [12].
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1.2 Myocardial infarction
Myocardial infarction (MI) can be defined from a number of different perspectives related to clinical, electrocardiographic (ECG), biochemical and pathologic characteristics. Myocardial infarction is defined as myocardial cell death due to prolonged ischemia. Cell death is categorized pathologically as either coagulation or contraction band necrosis, or both, which usually evolves through oncosis, but can result to a lesser degree from apoptosis. In studies of disease prevalence by the World Health Organization (WHO), MI was defined by a combination of two of three characteristics: typical symptoms (i.e., chest discomfort), enzyme rise and a typical ECG pattern involving the development of Q waves.
It is accepted that the term MI reflects a loss of cardiac myocytes (necrosis) caused by prolonged ischemia. Ischemia is the result of a perfusion-dependent imbalance between supply and demand. Ischemia in a clinical setting can be identified from the patient’s history and from the ECG. Possible ischemic symptoms include chest, epigastric, arm, wrist or jaw discomfort with exertion or at rest. The presence or absence and the amount of myocardial damage resulting from prolonged ischemia
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can be assessed by a number of different means, including pathologic examination, measurement of myocardial proteins in the blood, ECG recordings (ST-T segment wave changes, Q waves), imaging modalities such as myocardial perfusion imaging, echocardiography and contrast ventriculography. [13]
1.3 Approaches for cardiac tissue engineering
Within tissue engineering (TE), one of the major research themes is scaffold design. A scaffold is a 3D construct that serves as temporary support for isolated cells to grow into new tissue before transplantation back to the host.. The design of the scaffold determines the functionality of the construct to a high extent. Although the final requirements depend on the specific purpose of the scaffold, several general characteristics and requirements need to be considered for all designs [14-17]. The scaffold should be/have:
biocompatible; the scaffold should provoke an appropriate biological response in a specific application and prevent any adverse response of the surrounding tissue [18,19]
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regeneration and remodelling of the extracellular matrix (ECM) into smaller non-toxic substances without interfering with the function of the surrounding tissue [20] promote cell attachment, spreading and proliferation; vital for the regulation of cell growth and differentiation [21]
suitable mechanical strength; its strength should be comparable to in vivo tissue at the site of implantation as evidently, a scaffold requires more flexibility or rigidity depending on the application in e.g. cardiovascular versus bone prostheses [22]
good transport properties; to ensure sufficient nutrient transport towards the cells and removal of waste products the scaffold should be highly porous with good pore connectivity, however, it should maintain sufficient mechanical strength implying optimization of porosity [14, 23-25]
easy to connect to the vascularization system of the host; to ensure good nutrient supply throughout the scaffold post‐implantation, the scaffold should be connected to the natural nutrient supplying system [14, 23 ,25]
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research suggests that the introduction of e.g. surface topography into the scaffold improves tissue organization leading to increased tissue function [26-29]
