Incorporation of Adeno-Associated Virus Encoding Vascular Endothelial Growth Factor into a Biodegradable Elastomeric Scaffold for Improved Function in the Ischemic Rat Heart.

Abstract

Ischemic heart disease morbidity and mortality ensue as the ventricle remodels, and cardiac function is lost following myocardial infarction. Previous studies have shown that applying a biodegradable, elastic epicardial patch onto the ischemic cardiac wall preserves the cardiac function and alters the remodeling process. In this report, the capacity to deliver a recombinant adeno-associated virus (AAV) encoding human vascular endothelial growth factor (VEGF) was evaluated to determine if it would provide benefit beyond a patch alone. Coaxial electrospinning of a poly(ether ester urethane) urea generated microfibrous patches with fibers loaded in their core with VEGF-AAV in poly(ethylene oxide) or vehicle alone. In a rat infarction model, epicardial patches were placed 3 days post-infarction. Over an 8 week period following the intervention, end-diastolic area was lower and ejection fraction greater in the patch-VEGF group compared with the control patch and sham surgery groups. There was also a greater number of α-SMA-positive cells, blood vessels, and positive immunostaining for VEGF in the patch-VEGF group compared with groups having patches lacking VEGF. The approach of combining mechanical (patch) and biofunctional (controlled release angiogenic therapy) support through a scaffold-based gene vector transfer approach may be an effective option for dealing with the adverse ventricular wall remodeling that leads to end-stage cardiomyopathy.