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

International journal of cardiology

PubMedID: 27379917

Rocca DG, Willenberg BJ, Qi Y, Simmons CS, Rubiano A, Ferreira LF, Huo T, Petersen JW, Ruchaya PJ, Wate PS, Wise EA, Handberg EM, Cogle CR, Batich CD, Byrne BJ, Pepine CJ. An injectable capillary-like microstructured alginate hydrogel improves left ventricular function after myocardial infarction in rats. Int J Cardiol. 2016;220149-154.
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).