Effect of injectable alginate implant on cardiac remodeling and function after recent and old infarcts in rat.
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.


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.
Landa
Natali
N
Neufeld Cardiac Research Institute, Sheba Medical Center, Tel-Aviv University, Tel-Hashomer 52621, Israel.
Miller
Liron
L
Feinberg
Micha S
MS
Holbova
Radka
R
Shachar
Michal
M
Freeman
Inbar
I
Cohen
Smadar
S
Leor
Jonathan
J
D000464:Alginates / Q000008:administration & dosage / Q000737:chemistry / Q000494:pharmacology / Q000627:therapeutic use*; D000818:Animals; D001672:Biocompatible Materials / Q000008:administration & dosage / Q000737:chemistry / Q000494:pharmacology / Q000627:therapeutic use*; D002921:Cicatrix / Q000000981:diagnostic imaging / Q000473:pathology; D004334:Drug Administration Schedule; D004353:Drug Evaluation, Preclinical; D020723:Glucuronic Acid / Q000008:administration & dosage / Q000737:chemistry / Q000494:pharmacology / Q000627:therapeutic use; D006603:Hexuronic Acids / Q000008:administration & dosage / Q000737:chemistry / Q000494:pharmacology / Q000627:therapeutic use; D020100:Hydrogels / Q000008:administration & dosage / Q000494:pharmacology / Q000627:therapeutic use*; D017379:Hypertrophy, Left Ventricular / Q000000981:diagnostic imaging / Q000209:etiology / Q000517:prevention & control*; D015552:Injections, Intralesional; D008297:Male; D008422:Materials Testing; D009203:Myocardial Infarction / Q000000981:diagnostic imaging / Q000188:drug therapy* / Q000473:pathology / Q000601:surgery; D032383:Myocytes, Cardiac / Q000637:transplantation; D011897:Random Allocation; D051381:Rats; D017207:Rats, Sprague-Dawley; D014463:Ultrasonography; D018487:Ventricular Dysfunction, Left / Q000000981:diagnostic imaging / Q000209:etiology / Q000517:prevention & control*; D020257:Ventricular Remodeling / Q000187:drug effects*; D014783:Viscosity
D000464:Alginates; D001672:Biocompatible Materials; D006603:Hexuronic Acids; D020100:Hydrogels; D020723:Glucuronic Acid