Materials Science and Tissue Engineering: Repairing the Heart Milica Radisic, PhD, Karen L. Christman, PhD  Mayo Clinic Proceedings  Volume 88, Issue 8, Pages 884-898 (August 2013) DOI: 10.1016/j.mayocp.2013.05.003 Copyright © 2013 Mayo Foundation for Medical Education and Research Terms and Conditions

Figure 1 Pluripotent stem cell–derived cardiac patches. A, Vascularization of cardiac patches based on cardiomyocytes (CMs) derived from human embryonic stem cells (hESCs) can be enhanced by co-culture with endothelial cells (ECs) and either mouse embryonic fibroblasts (MEFs) or mesenchymal stem cells (MSCs). B, A human induced pluripotent stem cell–based cardiac patch can be implanted onto the heart of an athymic rat and persist for 1 week. The graft-host interface is shown on (top) β-myosin heavy chain staining and (bottom) α-actinin staining. From Circ Res,61 with permission. Mayo Clinic Proceedings 2013 88, 884-898DOI: (10.1016/j.mayocp.2013.05.003) Copyright © 2013 Mayo Foundation for Medical Education and Research Terms and Conditions

Figure 2 Cardiac patches derived from mouse parthenogenetic cells. A, Patches were conditioned by mechanical stimulation (scale bar, 1 mm). B, They were used to repair infarcted myocardium of the mouse donors (scale bar, 2 mm). C, Patch implantation resulted in the improvement of anterior wall thickening at diastole (∗P<.05 vs control). Data are given as mean ± SD. AWThF = anterior wall thickening fraction; Ctrl = control; EHM = engineered heart muscle; F-EHM = fixed engineered heart muscle; GFP = green fluorescent protein. From J Clin Invest,73 with permission. Mayo Clinic Proceedings 2013 88, 884-898DOI: (10.1016/j.mayocp.2013.05.003) Copyright © 2013 Mayo Foundation for Medical Education and Research Terms and Conditions

Figure 3 Engineering of vascularized myocardium by control of the topography and presentation of angiogenic growth factors. A, A polydimethyl siloxane (PDMS) stamp with topographic cues (grooves and ridges) is coated with collagen:chitosan hydrogel desired for the controlled release of an angiogenic factor thymosin β4(Tβ4). The topographic cues guide the outgrowth of capillaries from an artery and vein, resulting in a microvessel bed around which cardiomyocytes are seeded. B, Microvascular outgrowths are connected by day 21. Arrows indicate locations of artery and vein explants. C, Confocal micrographs indicate the presence of open lumens (xz, yz, and xy refer to different imaging planes). D, Vascularized cardiac tissue. From Proc Natl Acad Sci U S A,90 with permission. Mayo Clinic Proceedings 2013 88, 884-898DOI: (10.1016/j.mayocp.2013.05.003) Copyright © 2013 Mayo Foundation for Medical Education and Research Terms and Conditions

Figure 4 Delivery approaches for injectable biomaterial scaffolds. Similar to cell injections, biomaterial scaffolds can be delivered via transcoronary infusion (A), which involves infusion of the material across the leaky coronary vessels immediately after myocardial infarction; transendocardial injection (B), which involves catheter placement inside the chamber of the left ventricle and injection across the endocardium; or direct epicardial injection (C), which requires a surgical approach to access the epicardium. Transendocardial and direct epicardial injection involve puncture with a needle and targeted injection into the infarct area. From Heart Lung Circ,109 with permission. Mayo Clinic Proceedings 2013 88, 884-898DOI: (10.1016/j.mayocp.2013.05.003) Copyright © 2013 Mayo Foundation for Medical Education and Research Terms and Conditions

Figure 5 Transcoronary delivery of alginate. Alginate, which is cross-linked with Ca2+, was delivered via a catheter-based transcoronary infusion in a porcine myocardial infarction (MI) model. Given the leaky vasculature and high extracellular Ca2+ level in an acute MI, the material is able to pass through the vasculature and gel once inside the tissue. The white material is visible (A) on the epicardial surface of the infarct and (B) in tissue slices. LAD = left anterior descending coronary artery; LV = left ventricular. From J Am Coll Cardiol,110 with permission. Mayo Clinic Proceedings 2013 88, 884-898DOI: (10.1016/j.mayocp.2013.05.003) Copyright © 2013 Mayo Foundation for Medical Education and Research Terms and Conditions

Figure 6 Increased cardiac muscle using an acellular myocardial matrix hydrogel. In a porcine myocardial infarction model, percutaneous transendocardial injections of a decellularized myocardial extracellular matrix–based hydrogel were performed 2 weeks after myocardial infarction. Three months after injection, there was significantly more cardiac muscle (*) found at the endocardium (A) after matrix treatment compared with (B) controls. Images are of trichrome-stained heart sections, in which muscle is stained red and collagen is stained blue. From Sci Transl Med,8 with permission. Mayo Clinic Proceedings 2013 88, 884-898DOI: (10.1016/j.mayocp.2013.05.003) Copyright © 2013 Mayo Foundation for Medical Education and Research Terms and Conditions