Abstract 19323: Extracellular Matrix Biomaterial Promotes Cardiac Repair Through an Active Bio-Inductive Fibroblast Growth Factor-2 Dependent Mechanism
Introduction: We previously demonstrated that epicardial application of extracellular matrix (ECM) biomaterial prevents LV remodeling and improves functional recovery following myocardial infarction (MI). In this study we aim to determine if the underlying mechanism of benefit is a consequence of the bio-inductive properties of the ECM biomaterial.
Hypothesis: We hypothesize that ECM biomaterial will promote functional recovery after ischemic injury by stimulating vasculogenesis through a bio-inductive effect.
Methods: Biologically active ECM biomaterial (CorMatrix-ECM) was compared to ECM biomaterial inactivated by chemical treatments. The paracrine response of human cardiac fibroblasts (N=6) to ECM biomaterial was characterized in vitro. In vivo active (N=16) or inactive (N=16) ECM biomaterial was surgically applied to the infarcted myocardium following coronary artery ligation in a rat model. Indices of cardiac performance were quantified by pressure volume loop analysis 14 weeks post-MI.
Results: Human cardiac fibroblast treated with active ECM biomaterial demonstrated increased vasculogenic growth factor production compared to inactive ECM biomaterial treated cells (FGF-2: 7.09±4.05 vs. 2.63±1.40 fold change; P=0.011; VEGF: 2.84±2.19 vs. 0.79±0.62 fold change; P=0.030; HGF: 8.72±6.99 vs. 1.12±0.71 fold change; P=0.049). Animals treated with active ECM biomaterial demonstrated functional recovery beyond inactive ECM biomaterial treated animals (EF: 40.50±7.47% vs. 32.74±9.31%; P=0.022). Increased vascularity was observed within the infarcted myocardium of active ECM biomaterial treated animals (active: 16.56±2.97 vs. inactive: 10.81±2.23 blood vessels per high power field; P<0.001). In vitro, active ECM biomaterial also increased vascular network formation of human endothelial cells seeded in matrigel compared to inactive ECM biomaterial (total tubule length: 26.30±2.78mm vs. 21.98±2.86mm; P=0.009).
Conclusion: These data demonstrate that ECM biomaterial stimulates vasculogenesis through a FGF-2 dependent paracrine mechanism. This bio-inductive mechanism results in attenuated adverse LV remodeling and enhanced functional recovery when ECM biomaterial is applied following ischemic injury.
Author Disclosures: H.E. Mewhort: None. D.A. Svystonyuk: None. J.D. Turnbull: None. G. Teng: None. D.D. Belke: None. D.S. Park: None. D.G. Guzzardi: None. S. Kang: None. P.W. Fedak: Other Research Support; Modest; CorMatrix Cardiovascular Inc. donated the ECM-biomaterial used in this research. CorMatrix did NOT fund this research.
- © 2016 by American Heart Association, Inc.