Incorporation of Adeno-Associated Virus Encoding Vascular Endothelial Growth Factor into a Biodegradable Elastomeric...

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.