Intramyocardial Delivery of HMGB1 by a Novel Thermosensitive Hydrogel Attenuates Cardiac Remodeling and Improves Cardiac Function After Myocardial Infarction

Background: High-mobility group box 1 (HMGB1), a nuclear protein, has been recently reported to attenuate cardiac remodeling after myocardial infarction (MI). This study was designed to investigate whether this effect could be strengthened by local intramyocardial injection of HMGB1 along with a novel Dex-PCL-HEMA/PNIPAAm hydrogel and ascertain its possible mechanism of action. Methods: Rat models were induced by coronary artery ligation. Phosphate-buffered solution, Dex-PCL-HEMA/PNIPAAm hydrogel, HMGB1 in phosphate-buffered solution, or HMGB1 in hydrogel was injected into a peri-infarcted area of cardiac tissue immediately after MI. Results: The injection of HMGB1 along with hydrogel improved cardiac function and reduced collagen content. Additionally, the number of c-Kit(+)/Ki67(+), alpha-sarcomeric(+)/MEF2C(+), and alpha-sarcomeric(+)/Ki67(+) cells were increased significantly compared with the results of using either agent alone. Conclusions: HMGB1 injection with Dex-PCL-HEMA/PNIPAAm hydrogel attenuates cardiac remodeling and improves cardiac function after MI by inducing myocardial regeneration.