Abstract 13532: Sustained Release of Engineered Stromal Cell Derived Factor 1-alpha from Injected Hydrogels Effectively Recruits Endothelial Progenitor Cells and Preserves Ventricular Function Following Myocardial Infarction
Objective: Exogenously delivered chemokines have enabled neovasculogenic myocardial repair in models of ischemic cardiomyopathy, however these peptides have short half-lives in vivo limiting efficacy. In this study we hypothesized that a sustained release form of a synthetic analog of stromal cell derived factor 1alpha (engineered SDF analogue; ESA) induces continuous homing of endothelial progenitor cells and improves left ventricular function in a rat model of myocardial ischemia.
Methods: Our previously designed ESA peptide was synthesized with the addition of 5-hydroxy-rhodamine as a fluorophore tag. ESA was immobilized in a biodegradable hyaluronic acid based hydrogel chemically modified with hydroxyethyl methacrylate. Hydrogels containing 25 μ g ESA were crosslinked and an elution curve was calculated from the fluorescence intensity detected by a microplate reader. Chemotactic properties of the eluted ESA were studied at different time points using a transwell migration assay to evaluate endothelial progenitor cell migration. Finally, adult male Wistar rats were used to investigate sustained release ESA. After permanent ligation of the LAD, 100µl of either saline, hydrogel alone, or hydrogel + 25µg ESA was injected into the borderzone. At 4 weeks, each animal underwent hemodynamic analysis.
Results: After an initial burst, the hydrogel steadily released ESA over a period of 4 weeks (Figure 1A ). Additionally, the eluted ESA enhanced EPC chemotaxis when compared to hydrogel alone or PBS control (Figure 1B ). Rats that received hydrogel + ESA(n=5) had preserved ejection fractions (63.7%±8.0), cardiac output (43.6ml/min±11.6), and increased contractility (18.9±3.6) compared to saline controls (n=5, 39.5%±17.2 p=0.01, 27.3ml/min±4.8 p=0.02, 10.3±3.9 p<0.05).
Conclusion: We have developed a hydrogel delivery system with sustained release of a bioactive chemokine peptide over a 4 week period that preserves ventricular function in a rat model of MI.
- © 2012 by American Heart Association, Inc.