Bifunctional Supramolecular Hydrogel Alleviates Myocardial Ischemia/Reperfusion Injury by Inhibiting Autophagy and Apoptosis.

Generally, nitric oxide (NO) is an important multi-functional cardioprotective soluble gas molecule. However, it may be detrimental when in excessive levels or combined with O2- a kind of reactive oxygen species (ROS)-to form ONOO-. The latter will rapidly decompose to highly reactive oxidant components. ROS will be abundantly produced during the ischemia/reperfusion (I/R) procedure. Therefore, an NO donor coupled with another antioxidant would be a more promising strategy for I/R treatment. In this study, we report on a novel self-assembly supramolecular hydrogel capable of constantly releasing both NO and curcumin (Cur) simultaneously, and we found that the combinational treatment of Cur and NO from the gel could efficiently reduce I/R injuries. The underlining mechanism revealed that the hydrogel could reduce the ROS level and thus inhibit the expression of the ROS-associated p38 MAPK/NF-κB signaling pathway. Moreover, the hydrogel also significantly suppressed over-stimulated autophagy and apoptosis during I/R treatment which was responsible for mediating severe post-ischemia myocardial cell death. The results indicated that our supramolecular hydrogel was a promising biomaterial for the treatment of myocardial I/R injuries.