Cardiovascular Engineering and Technology, Vol. 5, No. 4, December 2014 ( 2014) pp. 281–307 DOI: 10.1007/s13239-014-0193-7
Engineering Angiogenesis for Myocardial Infarction Repair: Recent Developments, Challenges, and Future Directions MOHAMMAD IZADIFAR,1 MICHAEL E. KELLY,1,2 and XIONGBIAO CHEN1,3 1
Division of Biomedical Engineering, College of Engineering, University of Saskatchewan, Saskatoon SK, Canada; 2Department of Surgery, College of Medicine, University of Saskatchewan, Saskatoon, SK, Canada; and 3Department of Mechanical Engineering, University of Saskatchewan, Saskatoon, SK, Canada (Received 9 June 2014; accepted 23 August 2014; published online 4 September 2014) Associate Editor Ajit P. Yoganathan oversaw the review of this article.
40% of all fatalities, more than all cancers combined.188 Each year, an estimated ~620,000 Americans are hospitalized due to myocardial infarction or die due to coronary heart disease, and ~295,000 have a recurrent coronary attack.70 Heart defects are also the most common congenital defects and the leading cause of death in the first year of life.189 Recognized as a critical public health issue worldwide, heart failure is caused by various cardiovascular diseases including acute myocardial infarction, ischemic cardiomyopathy, and idiopathic cardiomyopathy.187 Despite recent achievements in drug-eluting stents,152 off-pump coronary artery bypass grafting,175 mitral valve repair and left ventricular reconstruction surgery,8 and permanent pacemakers with left ventricle resynchronization devices,230 millions of people continue to suffer from heart failure.18,46,93,232 The heart is a terminally differentiated organ that fails to repair itself because of the intrinsic inability of damaged heart tissue to regenerate,51,106,179 so the large number of patients worldwide who survive myocardial infarction and develop advanced heart failure face largely unresolvable issues.91 At present, heart transplantation is the best solution for patients with end-stage heart failure. However, donor supply is declining and creating an increasing gap between supply and demand for heart replacement therapies. Left ventricular assist devices may provide a temporary therapeutic option for patients with pump failure but do not provide a definitive therapy.47 Thus, there has been great interest in alternative therapeutic strategies to reverse this common and deadly disease. Regenerative medicine and tissue engineering are rapidly growing areas that aim to maintain, replace, restore, or enhance the functionality of damaged, lost, or degenerated tissues/organs using combinations of
Abstract—Myocardial infarction is a cardiovascular disorder that remains a critical health issue worldwide. Because of its intrinsic inability to regenerate, cardiac tissue fails to repair itself after myocardial infarction. Cardiovascular engineering is a promising approach to regenerating myocardium for myocardial infarction repair. Despite explosive growth in research and interest in this field, cardiovascular regenerative medicine faces many challenges, with the need for rapid vascularization being the most pressing. Due to the high metabolic demand of cardiac cells, myocytes transplanted or implanted via cardiac scaffolds in the infarcted region do not survive without the timely formation of a microvascular network in the infarcted area or within the scaffolds. To address this issue, various strategies have been developed based on angiogenesis stimulation, prevascularization, and inosculation to promote microvascular network formation within the cardiac scaffolds. This paper describes cardiac tissue engineering strategies, key challenges in cardiovascular regenerative medicine, and various vascularization strategies, with an aim to review recent advances and developments in engineering vascularization and inosculation approaches towards the rapid integration of cardiac scaffolds, once implanted, with the host tissue. Challenges in engineering angiogenesis and future directions to address the issue of rapid inosculation are also discussed. Keywords—Angiogenesis, Cardiovascular, Cardiac tissue engineering, Myocardial infarction, Tissue engineering, Vascularization.
INTRODUCTION Cardiovascular disease and myocardial infarction are leading causes of death that account for nearly
Address correspondence to Mohammad Izadifar, Division of Biomedical Engineering, College of Engineering, University of Saskatchewan, Saskatoon SK, Canada. Electronic mail: mohammad.
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281 1869-408X/14/1200-0281/0
2014 Biomedical Engineering Society
