Abstract 422: Transcoronary Delivery of a Novel Alginate-Based Biomaterial Improves Cardiac Remodeling and Function after Myocardial Infarction in Pig
BACKGROUND: Injection of a designer biomaterial scaffold to replace the injured extracellular matrix (ECM) can enhance mechanical strength of the scar and may have an instructive role for cell assembling during healing and repair of the infarct. The present study aimed to determine the feasibility and efficacy of transcoronary injection of a novel, resorbable, alginate-based biomaterial to repair the infarcted myocardium.
METHODS AND RESULTS: We developed a novel calcium cross-linked alginate solution with the unique capacity to undergo phase transition into a hydrogel after injection into the infarct thereby acting as a mechanical tissue stabilizer. To test this new biomaterial solution in MI model, anterior MI was induced in domestic pigs (n = 9) by percutaneous, 90 min occlusion of mid LAD coronary artery. At 3– 4 days after MI, the biomaterial (2 ml) was injected selectively into the infarct through the infarct-related artery. To track the injected biomaterial, biotin-labeled cross-linked alginate was used. A few hours later, the hearts were harvested and histological examination showed that the alginate solution infiltrated into the infarct and transformed into hydrogel implant. Serial echocardiography and MRI studies were performed in another group of MI pigs (n = 21) treated with intracoronary injection of the alginate solution (1,2 and 4 ml) or saline (control), before and 2 months after injection. At 2 months, alginate biomaterial solution prevented LV diastolic dilatation, compared with control (0.3 ± 3.9 vs. 44.3 ± 8.1%; p<0.001). Furthermore, alginate injection reversed LV systolic dilatation, compared with control (−12.2 ± 6.3 vs. 48.1 ± 22.1; p<0.001), and improved global and regional LV function. Postmortem analysis showed that the alginate biomaterial injection increased scar thickness, compared with control (3 ± 0.2 vs. 1.9 ± 0.3 mm; p<0.01).
CONCLUSIONS: The present study shows, for the first time that transcoronary injection of alginate biomaterial solution is safe and effective in preventing LV remodeling and dysfunction after MI. Our findings suggest a new catheter-based, acellular option to facilitate myocardial repair and prevent adverse remodeling and dysfunction.