A paintable and adhesive hydrogel cardiac patch with sustained release of ANGPTL4 for infarcted heart repair

The infarcted heart undergoes irreversible pathological remodeling after reperfusion involving left ventricle dilation and excessive inflammatory reactions in the infarcted heart, frequently leading to fatal functional damage. Extensive attempts have been made to attenuate pathological remodeling in infarcted hearts using cardiac patches and anti-inflammatory drug delivery. In this study, we developed a paintable and adhesive hydrogel patch using dextran-aldehyde (dex-ald) and gelatin, incorporating the anti-inflammatory protein, ANGPTL4, into the hydrogel for sustained release directly to the infarcted heart to alleviate inflammation. We optimized the material composition, including polymer concentration and molecular weight, to achieve a paintable, adhesive hydrogel using 10% gelatin and 5% dex-ald, which displayed in-situ gel formation within 135 s, cardiac tissue-like modulus (40.5 kPa), suitable tissue adhesiveness (4.3 kPa), and excellent mechanical stability. ANGPTL4 was continuously released from the gelatin/dex-ald hydrogel without substantial burst release. The gelatin/dex-ald hydrogel could be conveniently painted onto the beating heart and degraded in vivo. Moreover, in vivo studies using animal models of acute myocardial infarction revealed that our hydrogel cardiac patch containing ANGPTL4 significantly improved heart tissue repair, evaluated by echocardiography and histological evaluation. The heart tissues treated with ANGPTL4-loaded hydrogel patches exhibited increased vascularization, reduced inflammatory macrophages, and structural maturation of cardiac cells. Our novel hydrogel system, which allows for facile paintability, appropriate tissue adhesiveness, and sustained release of anti-inflammatory drugs, will serve as an effective platform for the repair of various tissues, including heart, muscle, and cartilage.