An injectable capillary-like microstructured alginate hydrogel improves left ventricular function after myocardial infarction in rats

Int J Cardiol. 2016 Oct 1:220:149-54. doi: 10.1016/j.ijcard.2016.06.158. Epub 2016 Jun 25.

Abstract

Background: A new post-myocardial infarction (MI) therapy is injection of high-water-content polymeric biomaterial gels (hydrogels) into damaged myocardium to modulate cardiac negative remodeling and preserve heart function.

Methods: We investigated the therapeutic potential of a novel gelatinized alginate hydrogel with a unique microstructure of uniform capillary-like channels (termed Capgel). Shortly (48h) after induced anterior MI, Sprague Dawley rats received intramyocardial injection of Capgel directly into the antero-septal wall at the infarct border zone (n=12) or no injection (n=10, controls). Echocardiograms were performed at 48h (week 0) and 4weeks (week 4) to evaluate left ventricular function.

Results: Echocardiograms showed 27% improvement of left ventricular systolic function over time with gel injection: fractional shortening increased from 26±3% at week 0 to 33±2% at week 4 (p=0.001). Capgel was present at the injection site after 4weeks, but was minimal at 8weeks. The remaining gel was heavily populated by CD68(+) macrophages with CD206(+) clusters and blood vessels. An in vitro experiment was performed to assess Angiotensin-(1-7) released from Capgel. Angiotensin-(1-7) was released from the Capgel in a sustained manner for 90days.

Conclusions: Use of Capgel, a degradable, bioactive hydrogel composed of gelatinized capillary-alginate gel, appears safe for intramyocardial injection, is associated with improved left ventricular function after MI in rats, and may provide a long-term supply of Angiotensin-(1-7).

Keywords: Capillary-like channels; Gelatinized alginate hydrogel; Myocardial infarction.

MeSH terms

  • Alginates* / chemistry
  • Alginates* / pharmacology
  • Angiotensin I* / chemistry
  • Angiotensin I* / pharmacology
  • Animals
  • Biocompatible Materials / chemistry
  • Biocompatible Materials / pharmacology
  • Disease Models, Animal
  • Echocardiography / methods
  • Gelatin / pharmacology
  • Glucuronic Acid / chemistry
  • Glucuronic Acid / pharmacology
  • Hexuronic Acids / chemistry
  • Hexuronic Acids / pharmacology
  • Hydrogels / pharmacology
  • Injections, Intralesional / methods
  • Myocardial Infarction* / physiopathology
  • Myocardial Infarction* / therapy
  • Peptide Fragments* / chemistry
  • Peptide Fragments* / pharmacology
  • Rats
  • Rats, Sprague-Dawley
  • Treatment Outcome
  • Ventricular Function, Left / physiology*
  • Ventricular Remodeling / drug effects*

Substances

  • Alginates
  • Biocompatible Materials
  • Hexuronic Acids
  • Hydrogels
  • Peptide Fragments
  • Glucuronic Acid
  • Gelatin
  • Angiotensin I
  • angiotensin I (1-7)