Surgical Application of a Novel Biomaterial Enhances Post-MI Functional Recovery by Stimulating Vasculogenesis Through an Active Bio-Inductive Mechanism

BACKGROUND: Epicardial infarct repair (EIR) using a bio-inductive extracellular matrix (ECM) biomaterial is a novel surgical approach that targets the infarcted myocardium to enhance myocardial repair. We previously... [ view full abstract ]

BACKGROUND: Epicardial infarct repair (EIR) using a bio-inductive extracellular matrix (ECM) biomaterial is a novel surgical approach that targets the infarcted myocardium to enhance myocardial repair. We previously demonstrated that EIR prevents maladaptive LV remodeling and improves functional recovery post-MI. To determine whether these benefits are a consequence of passive biomechanical restraint or bio-inductive properties of the biomaterial we explored the mechanisms by which EIR enhances myocardial repair following ischemic injury.
METHODS AND RESULTS: EIR performed using biologically active ECM-biomaterial (CorMatrix Cardiovascular Inc., GA, USA) was compared to EIR performed using the same ECM-biomaterial biologically inactivated by gluteraldehyde-fixation. Active (N=16) or inactive (N=16) ECM-biomaterial was surgically applied to the epicardial surface of the infarcted myocardium following permanent coronary artery ligation in a rat model. Indices of cardiac performance, quantified by echocardiography and pressure volume loop analysis 14- weeks post-treatment, demonstrated EIR with active ECM-biomaterial resulted in functional recovery compared to inactive ECM-biomaterial-treated animals (ejection fraction: 40.50±7.47% vs. 32.74±9.31%; P=0.02; contractility: 0.847±0.310mmHg/μL vs. 0.607±0.272mmHg/μL; P=0.007). 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; Figure). An increase in the number of epicardial progenerator cells, identified by nuclearization of β-catenin, was also observed in active ECM-biomaterial-treated animals.
CONCLUSION: These data suggest that EIR with a biologically active biomaterial enhances myocardial repair through a bio-inductive mechanism beyond passive infarct restraint. The epicardial application of ECM-biomaterial stimulates epicardial progenitor cell mobilization and increases vasculogenesis to enhance functional recovery post-MI.