Effect of Injectable Alginate Implant on Cardiac Remodeling and Function After Recent and Old Infarcts in Rat

TLDR

Adverse cardiac remodeling and heart failure after myocardial infarction are driven by excessive extracellular matrix damage. The study tested whether injecting an in‑situ forming alginate hydrogel into recent and old infarcts could scaffold the scar and reduce remodeling and dysfunction. A calcium‑crosslinked, low‑viscosity alginate solution was injected into rat infarcts, where it rapidly phase‑transformed into a hydrogel scaffold that was later replaced by connective tissue. Alginate injection increased scar thickness, attenuated LV dilation and dysfunction in both recent and old infarcts, with effects comparable or superior to neonatal cardiomyocyte transplantation.

Abstract

Background— Adverse cardiac remodeling and progression of heart failure after myocardial infarction are associated with excessive and continuous damage to the extracellular matrix. We hypothesized that injection of in situ–forming alginate hydrogel into recent and old infarcts would provide a temporary scaffold and attenuate adverse cardiac remodeling and dysfunction. Methods and Results— We developed a novel absorbable biomaterial composed of calcium-crosslinked alginate solution, which displays low viscosity and, after injection into the infarct, undergoes phase transition into hydrogel. To determine the outcome of the biomaterial after injection, calcium-crosslinked biotin-labeled alginate was injected into the infarct 7 days after anterior myocardial infarction in rat. Serial histology studies showed in situ formation of alginate hydrogel implant, which occupied up to 50% of the scar area. The biomaterial was replaced by connective tissue within 6 weeks. Serial echocardiography studies before and 60 days after injection showed that injection of alginate biomaterial into recent (7 days) infarct increased scar thickness and attenuated left ventricular systolic and diastolic dilatation and dysfunction. These beneficial effects were comparable and sometimes superior to those achieved by neonatal cardiomyocyte transplantation. Moreover, injection of alginate biomaterial into old myocardial infarction (60 days) increased scar thickness and improved systolic and diastolic dysfunction. Conclusions— We show for the first time that injection of in situ–forming, bioabsorbable alginate hydrogel is an effective acellular strategy that prevents adverse cardiac remodeling and dysfunction in recent and old myocardial infarctions in rat.