Rebuilding Postinfarcted Cardiac Functions by Injecting TIIA@PDA Nanoparticle-Cross-linked ROS-Sensitive Hydrogels

Abstract

Drug-loaded injectable hydrogels have been proven to possess huge potential for applications in tissue engineering. However, increasing the drug loading capacity and regulating the release system to adapt to the microenvironment after myocardial infarction face a huge challenge. In this research, an ROS-sensitive injectable hydrogel strengthened by self-nanodrugs was constructed. A hyperbranched ROS-sensitive macromer (HB-PBAE) with multiacrylate end groups was synthesized through dynamic controlled Michael addition. Meanwhile, a simple protocol based on dopamine polymerization was employed to generate a polydopamine (PDA) layer deposited on the tanshinone IIA (TIIA) nanoparticles (NPs) formed from spontaneous hydrophobic self-assembly. The HB-PBAE reacted with thiolate-modified hyaluronic acid (HA-SH) to form an in situ hydrogel, where TIIA@PDA NPs can be conveniently entrapped through the chemical cross-link between thiolate and quinone groups on PDA, which doubles the modulus of hydrogels. The in vivo degradation behavior of the hydrogels was characterized by MRI, exhibiting a much slower degradation behavior that is markedly different from that of in vitro. Importantly, a significant improvement of cardiac functions was achieved after hydrogel injection in terms of increased ejection fraction and decreased infarction size, accompanied by inhibition of the expression of inflammation factors, such as IL-1β, IL-6, and TNF-α.