Injectable Alginate Scaffold with Staged Transplantation of Fetal Cardiomyocytes Improves Infarct Healing and Cardiac Remodeling in Rat

Injection of a biomaterial scaffold into the infarcted myocardium can replace the injured extracellular matrix and improve the mechanical strength of the scar. The present study aimed to determine and compare the effect of novel injectable alginate scaffold, with or without staged cardiomyocyte transplantation, with injectable collagen scaffold, or saline on left ventricular (LV) remodeling and function after myocardial infarction (MI) in rat. We developed a novel injectable, absorbable biomaterial composed of a calcium cross-linked alginate solution, which displays low viscosity and undergoes phase transition into hydrogel after injection into the infarct. Rats (n=58) were subjected to anterior MI and subsequently treated with injection of alginate biomaterial (n=22), collagen (n=12), or saline (n=12) into the infarct. One week later, 10 of 22 biomaterial-treated rats and 10 MI rats received rat fetal cardiomyocyte transplantation (1×10 6 cells) into the scar. Hemodynamic studies, performed with a pressure-volume system (Millar instruments) 2 months after MI, showed that LV end-diastolic and systolic volumes were smaller in animals treated with injectable alginate scaffold, with and without staged cell transplantation, compared with animals treated with injectable collagen scaffold or saline (426 ±14 and 549±42 vs 661±40 and 623±53 μL, p=0.01; and 349±2 and 448±42 vs 607±49 and 552±60 μL, p=0.03). Postmortem morphometric analysis of the hearts showed that the area of collagen in the infarct was significantly lower in alginate, alginate with staged cardiomyocyte transplantation and in cardiomyocyte-treated animals, compared with collagen-treated and control animals (p< 0.001). Injectable alginate scaffold with staged transplantation of fetal cardiomyocytes can improve the favorable effects of injectable alginate scaffold on infarct repair and cardiac remodeling after MI.