Domenico G Della Rocca1, Bradley J Willenberg2, Yanfei Qi1, Chelsey S Simmons3, Andres Rubiano3, Leonardo F Ferreira4, Tianyao Huo5, John W Petersen1, Prashant J Ruchaya6, Prateek S Wate2, Elizabeth A Wise7, Eileen M Handberg1, Christopher R Cogle7, Christopher D Batich2, Barry J Byrne8, Carl J Pepine9. 1. Division of Cardiovascular Medicine, Department of Medicine, College of Medicine, University of Florida, Gainesville, FL, USA. 2. Department of Materials Science and Engineering, College of Engineering, University of Florida, Gainesville, FL, USA. 3. Department of Mechanical and Aerospace Engineering, College of Engineering, University of Florida, Gainesville, FL, USA. 4. Department of Applied Physiology and Kinesiology, College of Health and Human Performance, University of Florida, Gainesville, FL, USA. 5. Division of Biostatistics, Department of Epidemiology and Health Policy Research, College of Medicine, University of Florida, Gainesville, FL, USA. 6. Department of Physiology and Functional Genomics, College of Medicine, University of Florida, Gainesville, FL, USA. 7. Division of Hematology & Oncology, Department of Medicine, College of Medicine, University of Florida, Gainesville, FL, USA. 8. Division of Cellular and Molecular Therapy, Department of Pediatrics, College of Medicine, University of Florida, Gainesville, FL, USA. 9. Division of Cardiovascular Medicine, Department of Medicine, College of Medicine, University of Florida, Gainesville, FL, USA. Electronic address: carl.pepine@medicine.ufl.edu.
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).
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).
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