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 (H2O2), 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 H2O2 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 H2O2 may be a novel strategy for diagnosing and treating bone defects.

A Multifunctional Composite Hydrogel That Rescues the ROS Microenvironment and Guides the Immune Response for Repair of Osteoporotic Bone Defects

“…[43] Therefore, it has a unique advantage in imaging deep tissues such as bone, as has been demonstrated in our previous study. [5] In vivo H 2 O 2 elimination by composite hydrogels was also investigated in our study (Figure 6). The results display the changes in ROS in the bone of osteoporotic mice for the first time.…”

“…Bone morphogenetic protein-2 (BMP-2)-associated peptide was loaded into hMNPs to promote bone repair. [5] In this study, MMS was prepared for the treatment of osteoporotic bone defects. Compared with previous hMNPs, MMS has a core-shell structure with porous CaP microspheres in the inner layer.…”

“…[33] We chose this material because we have proven that MnO 2 could effectively eliminate ROS and release O 2 , which is suitable for bone repair. [5] Mn-containing materials, such as MnO 2 nanoparticles, have frequently been used to treat various cancers in recent years. [34] However, recent studies have gradually excavated the role of Mn-containing materials in tissue regeneration.…”

“…In our previous study, the excessive ROS in the microenvironment of bone injury was used as a target for the diagnosis and treatment of bone injury. [5] ROS, mainly produced by mitochondria and nicotinamide adenine dinucleotide phosphate oxidase 1 enzyme, is highly expressed in osteoclasts. [6] ROS can promote osteoclastogenesis, conversely, the process of osteoclast formation stimulated by receptor activator of NF-κB ligand (RANKL) and macrophage-colony-stimulating factor (M-CSF) also increases the ROS level.…”

Arbutin-Modified Microspheres Prevent Osteoarthritis Progression by Mobilizing Local Anti-Inflammatory and Antioxidant Responses

“…Due to robust antioxidant properties, ARB-modi ed microspheres scavenge excessive ROS via the Nrf2-HO-1 signalling pathway. Li et al also demonstrated that hollow manganese dioxide nanoparticles (hMNPs) promoted bone defect repair by decomposing H 2 O 2 and generating oxygen to eliminate intracellular ROS [40]. Hence, we hypothesized that the dual regulation of in ammation and redox induced by GM-Lipo@ARB could boost cartilage regeneration in the microenvironment.…”