Abstract 10751: Pericardial Injection of Micronized Matrix Biomaterial Improves Post-Infarct Cardiac Function and Modulates Fibroblast Activity to Enhance Repair

Abstract

Introduction: Injection of micronized biomaterials into the pericardial space leverages bioinductive properties to enhance post-infarct cardiac repair. This less invasive, potentially bedside, approach enables early intervention. Micronized porcine small intestinal submucosal extracellular matrix (SIS-ECM) contains fibroblast growth factor 2 (FGF2) which reduce fibrosis and increase vasculogenesis. Hypothesis: Pericardial delivery of micronized SIS-ECM improves post-infarct cardiac function. It promotes a proangiogenic and antifibrotic fibroblast phenotype. Methods: Mice received coronary ligation (infarct) through an undisrupted pericardium followed by pericardial delivery of micronized SIS-ECM or saline control. Pressure-volume loops were at 28 days. Myocardial isolectin stain assessed small vessel density on confocal microscopy. Mouse 3T3 cell line fibroblasts in 3D collagen matrices were exposed to biomaterial-conditioned media or media control. Multiplex analyzed paracrine activity. Collagen gel contraction and MMP2 production assessed profibrotic phenotype. FGF2 inhibitor elucidated mechanism. Results: Mice receiving micronized SIS-ECM had lower ventricular stiffness (0.23±0.03 vs 0.39±0.05 mmHg/uL; p=0.01), higher ejection fraction (34.7±2.5 vs 26.9±2.8%; p<0.05) and higher stroke work (1510±138 vs 1066±152 μL/mmHg; p=0.04). The SIS-ECM group had higher normalized border zone isolectin mean fluorescence (0.82±0.04 vs 0.58±0.06; p=0.01). Micronized SIS-ECM attenuated collagen gel contraction (26±6 vs 56±5%; p=0.01) and MMP2 release (66±2 vs 83±3 ng/mL; p<0.01). Micronized SIS-ECM increased fibroblast VEGF production (904±79 vs 628±25; pg/mL). FGF2 inhibitor negated biomaterial effects, increasing gel contraction (27.3±5.3 vs 11.0±0.5%; p=0.04; inhibitor vs no inhibitor) and MMP-2 release (141±8 vs 100±6 ng/mL; p=0.02). Conclusions: Pericardial injection of micronized SIS-ECM attenuates profibrotic fibroblast activity, increases release of angiogenic VEGF protein, increases vasculogenesis on isolectin staining, and preserves post-infarct cardiac function. This less invasive strategy facilitates early intervention to attenuate maladaptive post-infarct structural remodeling.