Targeting Endogenous Hydrogen Peroxide at Bone Defects Promotes Bone Repair

Abstract Reactive oxygen species (ROS) plays a critical role in tissue repair, including bone. Therefore, detecting and regulating ROS is essential for monitoring and facilitating bone repair. In this study, for the first time, the spatiotemporal profile of ROS, represented by hydrogen peroxide (H 2 O 2 ), in the bone injury microenvironment using photoacoustic imaging technique is visualized. The ROS levels significantly increase upon bone injury, peak at a certain stage of bone healing, and then gradually decrease toward baseline level. To regulate ROS in the bone injury microenvironment, the use of hollow manganese dioxide nanoparticles (hMNPs), which are able to decompose H 2 O 2 and generate oxygen is explored. In vitro, hMNPs eliminate intracellular ROS to protect cells from oxidative damage and facilitate cell growth by releasing oxygen. In vivo, composite hydrogels containing gelatin methacryloyl (GelMA) and hMNPs (hMNP/GelMA) release oxygen and bone morphogenetic protein‐2 (BMP‐2)‐associated peptide in an “on‐demand” fashion in response to bone microenvironmental ROS change. Applying hMNP/GelMA composite hydrogels loaded with BMP‐2‐associated peptide (BhMNP/GelMA) significantly enhances bone formation in a rat critical‐sized calvarial defect. Together, findings from this study imply that the visualization and regulation of ROS such as H 2 O 2 may be a novel strategy for diagnosing and treating bone defects.