Abstract 1419: Biocompatible 3-Dimensional RGD-Modified Alginate Scaffold Designed to Enhance Cell Transplantation to Infarcted Myocardium
Introduction Cell transplantation strategies for cardiac repair are currently limited by poor survival of transplanted cells. Three dimensional scaffolds improve cell transplant survival after delivery to infarcted myocardium. We aimed to design a biocompatible porous 3D scaffold using custom purified alginate that augments cell viability. Two-dimensional surfaces coated with cyclic RGDfK peptides have been shown to improve cell viability. We hypothesized that covalent attachment of cRGDfK peptide to an alginate scaffold would improve cell viability in 3D. Methods Cyclic RGDfK peptide modified porous scaffolds were fabricated by freeze gelation and subsequently seeded with 3x10e6 neonatal rat cardiomyocytes or 3x10e6 neonatal rat cardiac fibroblasts. Cell containing scaffolds were cultured for one week and cell viability was determined by trypan blue exclusion. Scaffolds were implanted intramuscularly in rats (n=4) for 1 month to determine biocompatibility by multinucleated giant cell formation, compared to immunogenic suture material. Efficacy of circular scaffold (16 mm x 0.75 mm) application to the epicardial surface of rat hearts (n=12) was evaluated macroscopically and by ED-2 positive macrophage staining 1 week after transplantation. Results Scaffolds with interconnected pores (100–200 μm) allowed seeding and even distribution of cells. At 1 week, neonatal rat myocyte viability inside scaffolds increased from 3.3±1.2% (0 mg/g cRGDfK) to 12.3±0.1% (10 mg/g cRGDfk) to 28.9±7.3% (10 mg/g cRGDfk + gelatin) (P<0.05). Clusters of beating myocytes could be detected. Neonatal rat cardiac fibroblast viability increased from 48.8±21% (0 mg/g cRGDfK) to 77.2±3.2% (10 mg/g cRGDfK) (P<0.05). One month after intramuscular scaffold implantation, 1.2±0.7 multinucleated cells could be seen per HPF throughout the scaffold, vs 17.5±4.2 around immunogenic sutures (P<0.05). Scaffolds integrated with the epicardial surface 1 week after transplantation. ED-2 staining was negative. Conclusion Three dimensional scaffolds generated from custom purified alginate modified with cRGDfK peptide promote cardiac cell viability in vitro. Scaffolds are biocompatible and may be used to transplant cells to the myocardium by epicardial application.