A Reactive Oxygen Species Scavenging and O₂ Generating Injectable Hydrogel for Myocardial Infarction Treatment In vivo

Abstract

The excessive reactive oxygen species (ROS) and hypoxia deteriorate the inflammation‐related diseases such as myocardial infarction (MI), and thereby deter the normal tissue repair and recovery and further lead to severe fibrosis and malfunction of tissues and organs. In particular, the MI has become one of the leading causes of death nowadays. In this study, a novel type of injectable hydrogel with dual functions of ROS scavenging and O2 generating is fabricated for MI treatment in vivo. The hydrogel is formed within 3 s from the synthetic ROS‐cleavable hyperbranched polymers and methacrylate hyaluronic acid (HA‐MA) under UV‐irradiation. Addition of biocompatible and applicable catalase in vivo enables the further transition of H2O2, a major type of ROS, to O2 and H2O. Results of rat MI model demonstrate that this hydrogel can significantly remove excessive ROS, inhibit cell apoptosis, increase M2/M1 macrophage ratio, promote angiogenesis, reduce infarcted area, and improve cardiac functions. With the appropriate degradation rate, simple structure and composition without cell seeding, and very excellent MI therapeutic effect, this ROS scavenging and O2 generating hydrogel has a great promise to be applied clinically.

The Serum of MEF2D Expression in Patients with Myocardial Infarction, May be Clinical Indicators and it Mediated ROS Signaling by HDAC5

“…MI leads to abnormal intracellular environment caused by insu cient energy supply [19]. The compensatory increase in cardiac contraction can cause the increase in ROS level caused by NADPH in the cell membrane [20].…”

Nanoplatforms for Sepsis Management: Rapid Detection/Warning, Pathogen Elimination and Restoring Immune Homeostasis

“…Accumulated ROS and hypoxia in pathogenetic tissues delay tissue regeneration thus worsening myocardial infarction. To resolve this issue, Ding and coworkers synthesized ROS-cleavable hyperbranched polymers that coassembled with methacrylate HA to form an injectable hydrogel under UV irradiation [ 91 ]. Incorporation of biocompatible catalase conferred this hydrogel with H 2 O 2 degradative function for O 2 generation, and the ROS-cleavable polymers degraded once contacting with excessive ROS, contributing to drug release and ROS scavenging [ 91 ].…”

“…To resolve this issue, Ding and coworkers synthesized ROS-cleavable hyperbranched polymers that coassembled with methacrylate HA to form an injectable hydrogel under UV irradiation [ 91 ]. Incorporation of biocompatible catalase conferred this hydrogel with H 2 O 2 degradative function for O 2 generation, and the ROS-cleavable polymers degraded once contacting with excessive ROS, contributing to drug release and ROS scavenging [ 91 ]. The dual-action hydrogel platform showed advanced therapeutic efficacy against myocardial infarction, as indicated by removal of excessive ROS, inhibition of cell apoptosis, and improved angiogenesis, etc .…”

“…The dual-action hydrogel platform showed advanced therapeutic efficacy against myocardial infarction, as indicated by removal of excessive ROS, inhibition of cell apoptosis, and improved angiogenesis, etc . [ 91 ]. Methacrylated gelatin (GelMA) could chemically cross-link with N-(2-aminoethyl)–4-(4-(hydroxymethyl)–2-methoxy-5-nitrosophenoxy) butanamide (NB)-modified HA (HA-NB) through UV-triggered click reaction between aldehyde groups and amino groups [ 92 ].…”

Enabling in vivo Photocatalytic Activation of Rapid Bioorthogonal Chemistry by Repurposing Si-Rhodamine Fluorophores as Cytocompatible Far-Red Photocatalysts

“…69,70 Injectable materials that can form 3D hydrogels have the potential for creating better cancer xenograft models for the study of cancer biology. For example, LNCaP prostate cancer cells are poorly tumorigenic and generally require other types of cells or Matrigel to support tumor model generation 71,72 . Two-photon methods provide an approach for hydrogel patterning with high spatial resolution using far-red/NIR light.…”