Remodeling of ECM patch into functional myocardium in an ovine model: A pilot study.

Abstract

Previous studies have demonstrated that surgical patches comprised of small intestinal submucosa-derived extracellular matrix (ECM) have biological remodeling potential. This pilot study investigated histological, mechanical, and bioelectrical properties of an ECM patch implanted in the ovine right-ventricular outflow tract (RVOT). ECM patches (2 × 2 cm2 ) were implanted in four Western Range sheep (wether males, 37-49 kg, age <1 year) and explanted at 5 months (n = 2) and 8 months (n = 2). In vivo analysis included epicardial echocardiography and contact electrical mapping. Optical mapping was used to map electrical activity of two hearts on a Langendorff preparation. Mechanical testing quantified stiffness. Histological stains characterized structure, neovascularization, and calcification; immunohistochemistry (IHC) assessed cell phenotype. In vivo analysis showed that ECM patch tissue was contractile by M-mode and two-dimensional echocardiographic evaluation. In vivo electrical mapping, and optical mapping confirmed that ECM conducted an organized electrical signal. Mechanical testing of native and ECM patched RVOT tissue showed an elastic modulus of the implanted patch comparable to native tissue stiffness. At 5 and 8 months, the ECM had undergone extracellular matrix remodeling and neovascularization without calcification. The ECM was populated with locally aligned muscle cells positive for sarcomeric alpha-actinin, CD45, and troponin I and T. In sheep, the ECM patch appears to have the potential of remodeling to resemble native, functional ventricular tissue as evidenced by histological, mechanical, and electrical properties. © 2015 Wiley Periodicals, Inc. J Biomed Mater Res Part B: Appl Biomater, 104B: 1713-1720, 2016.