Drug-Loaded Mesoporous\nPolydopamine Nanoparticles\nin Chitosan Hydrogels Enable Myocardial Infarction Repair through\nROS Scavenging and Inhibition of Apoptosis

In this study, we synthesized mesoporous polydopamine\nnanoparticles\n(MPDA NPs) using an emulsion-induced interface assembly strategy and\nloaded epigallocatechin gallate (EGCG) into MPDA NPs via electrostatic\nattraction to form EGCG@MPDA NPs. In the post myocardial infarction\n(MI) environment, these interventions specifically aimed to eliminate\nreactive oxygen species (ROS) and facilitate the repair of MI. We\nfurther combined them with a thermosensitive chitosan (CS) hydrogel\n to construct an injectable composite hydrogel (EGCG@MPDA/CS hydrogel).\nUtilizing <i>in vitro</i> experiments, the EGCG@MPDA/CS\nhydrogel exhibited excellent ROS-scavenging ability of H9C2 cells\nunder the oxidative stress environment and also could inhibit their\napoptosis. The EGCG@MPDA/CS hydrogel significantly promoted left ventricular\nejection fraction (LVEF) in infarcted rat models post injection for\n28 days compared to the PBS group (51.25 ± 1.73% vs 29.31 ±\n0.78%, <i>P</i> < 0.05). In comparison to the PBS group,\nhistological analysis revealed a substantial increase in left ventricular\n(LV) wall thickness in the EGCG@MPDA/CS hydrogel group (from 0.58\n± 0.03 to 1.39 ± 1.11 mm, <i>P</i> < 0.05).\nThis work presents a novel approach to enhance MI repair by employing\nthe EGCG@MPDA/CS hydrogel. This hydrogel effectively reduces local\noxidative stress by ROS and stimulates the nuclear factor erythroid\n2-related factor 2 (Nrf2)/heme oxygenase-1 (HO-1) pathway.