Abstract 3548: Biodegradable Collagen Patch with Covalently Bound VEGF Improves Right Ventricular Repair
Successful heart repair with a cell-seeded patch requires improved methods to facilitate angiogenesis and permit survival and engraftment of the implanted cells. This study describes a novel method to induce angiogenesis within a surgically-implanted biodegradable patch: vascular endothelial growth factor (VEGF) covalently linked to a collagen backbone. Mouse recombinant VEGF165 was immobilized into a porous collagen scaffold using N′-ethylcarbodiimide hydrochloride (EDC) chemistry at high (1.2 μg/sponge) and low (0.3 μg/sponge) doses by varying the concentration of VEGF in a crosslinking solution. The collagen+VEGF patches (or collagen sponges without VEGF, as controls) were used to repair transmural defects surgically created in the right ventricular outflow tract of adult rat hearts (n=7/group). At 1 and 4 weeks post-implantation, the biomaterials were histomorphometrically analyzed for patch thickness, cellular density, angiogenesis and inflammatory cell infiltration. High-dose VEGF patches were thicker (p<0.001) than control and low-dose patches at 1 week post-implantation, and thicker (p<0.01) than control patches at 4 weeks. Blood vessel density was also increased in high-dose patches vs. controls at 1 and 4 weeks (p<0.05 and p<0.01, respectively). Blood vessel density correlated positively with patch thickness at 4 weeks (r=0.6728, p=0.023). Over the 3 week study duration, VEGF patches exhibited a 1.5-fold decrease in patch thickness, while control patches exhibited a 3.2-fold decrease. Angiogenesis was accomplished without an increase in inflammatory cell infiltration (p=0.39). Immobilized VEGF within cardiac grafts increased the resultant blood vessel density and patch thickness, and improved healing of the new right ventricular outflow tract. Covalent modification of biodegradable scaffolds improves the spatial presentation of growth factors compared to controlled release or gene therapy strategies. These enhanced biomaterials may improve the survival and engraftment of recruited or implanted cells, and may be ideal for the repair of congenital heart defects in children.