An injectable hydrogel to reverse the adverse microenvironment of diabetic infarcted heart

Abstract

A library of injectable hydrogels shows the promising outcomes to restore an infarcted heart. However, none of them has been designed to meet diabetic patients. Here, a proof-of-concept research to build an injectable hydrogel to reverse the adverse microenvironment of injured diabetic hearts is reported. A hyper-branched poly (beta amino ester) polymer is abundant in acrylate and phenylboronic acid (PAE-PBA) to achieve a fast crosslinking with thiolated hyaluronic acid (HA-SH) and form a dynamic complexing with the targeted drug. Andrographolide nanoparticles (ADG NPs) to inhibit the over-expressing inflammatory factors and supramolecular nanofibers (IGF-1-F) with a superior bioactivity to insulin-like growth factor 1 (IGF-1) to regulate autophagy and apoptosis are conveniently encapsulated into the hydrogels. After being administered in diabetic infarcted rat hearts, the dynamic borate bond between PBA and ADG were broken and the hydrogel were degraded, accompanying with a controllable release of ADG and IGF-1-F. This functional hydrogel contributed to a remarkable decrease in the expression of inflammatory factors, a sharp inhibition of the infaust autophagy and apoptosis, and an obvious promotion in angiogenesis, demonstrating a strong capability to reverse the adverse microenvironments. Meanwhile, the infarcted area and the fibrosis area were reduced by 17.9% and 33.5%, respectively, accompanying with a high expression of cardiac related protein and well-ordered histological structures, suggesting a favorable restoration in the heart functions. This research presents the first try to explore an injectable hydrogel to reverse the villainous microenvironments of a diabetic infarcted heart, showing prominent implications in myocardial tissue engineering.