Myocardial infarction (MI) exhibits a complicated and ever-accelerated pathological change involving excessive reactive oxygen species (ROS) and the up-regulation of pro-inflammatory cytokines in the initial stage,and a permanently inadequate blood supply.Herein,an injectable hydrogel fabricated by nanoparticles (NPs) knotted thiolated hyaluronic acid (HA-SH) was reported to reverse the hostile microenvironment and rebuild the heart functions after MI.Inspired by the composite shell-core structure of Ferrero chocolate sphere,a mimetic nanocarrier was designed to consist of the hydrophobic dimethyloxalylglycine (DMOG) NPs core and a thick polydopamine (PDA) shell formed by the self-polymerization of dopamine embedded with watersoluble drug epigallocatechin-3-gallate (EGCG) through π-π interactions.The resulted “Ferrero-like” NPs exhibited a “three-inone” capacity,namely loading two distinct drugs,elimination of ROS,and serving a crosslinker to knot HA-SH.“Ferrero-like”NPs and HA-SH could rapidly form a hydrogel that exhibited a stable mechanical property,high capability to capture ROS,and programmed release of EGCG and DMOG.Four weeks after deploying the “Ferrero-like” NPs knotted hydrogels into rat infarcted hearts,the ejection fraction (EF) increased by 23.7％,and the infarct size decreased by 21.1％,and the fibrotic area reduced by 24.4％.The outcomes of immunofluorescence staining and reverse transcription-polymerase chain reaction (RT-PCR) demonstrated a down-regulation of inflammatory factors (tumor necrosis factor-α (TNF-α),interleukin-1β (IL-1β),interferon-γ (IFN-γ)),up-regulation of vascular related growth factors (hypoxia inducible factor-1 α (HIF-1 α),vascular endothelial growth factor A (VEGFA),von Willebrand factor (vWF),angiopoietin-1 (Ang-1)) and cardiac-related mRNAs (gap junction protein (Cx43),Cadherin 2).All in all,in this report,a very simple approach to intertemporally address the intricate and ongoing pathological changes after MI by injecting “Ferrero-like” NPs knotted hydrogels is developed to reverse hostile microenvironment,with an ability to scavenge ROS,down-regulate pro-inflammation factors in the first stage,and promote angiogenesis in a long term,thereby contributing to a significant improvement of heart functions.