Rebuilding post-infarcted cardiac functions by injecting TIIA@PDA NPs-crosslinked ROS sensitive hydrogels

Drug-loaded injectable hydrogels have been proved to possess huge potential for the application in tissue engineering. However, increasing the drug loading capacity and regulating the release system to adapt to the microenvironment after myocardial infarction (MI) face a huge challenge. In this research, a ROS sensitive injectable hydrogel strengthened by self-nanodrugs was constructed. A hyperbranched ROS sensitive macromer (HB-PBAE) with multi-acrylate 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 crosslink between thiolate and quinone groups on PDA, which doubles the modulus of hydrogels. The in vivo degradation behavior of the hydrogels was characterized by Magnetic resonance imaging (MRI), exhibiting a much slower degradation behavior which 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, accompanying with inhibiting the expression of inflammation factors, such as interleukin-1β, interleukin-6, and tumor necrosis factor-α.