Understanding Reactive Oxygen Species in Bone Regeneration: A Glance at Potential Therapeutics and Bioengineering Applications

Abstract

Although the complex mechanism by which skeletal tissue heals has been well described, the role of reactive oxygen species (ROS) in skeletal tissue regeneration is less understood. It has been widely recognized that a high level of ROS is cytotoxic and inhibits normal cellular processes. However, with more recent discoveries, it is evident that ROS also play an important, positive role in skeletal tissue repair, specifically fracture healing. Thus, dampening ROS levels can potentially inhibit normal healing. On the same note, pathologically high levels of ROS cause a sharp decline in osteogenesis and promote nonunion in fracture repair. This delicate balance complicates the efforts of therapeutic and engineering approaches that aim to modulate ROS for improved tissue healing. The physiologic role of ROS is dependent on a multitude of factors, and it is important for future efforts to consider these complexities. This review first discusses how ROS influences vital signaling pathways involved in the fracture healing response, including how they affect angiogenesis and osteogenic differentiation. The latter half glances at the current approaches to control ROS for improved skeletal tissue healing, including medicinal approaches, cellular engineering, and enhanced tissue scaffolds. This review aims to provide a nuanced view of the effects of ROS on bone fracture healing which will inspire novel techniques to optimize the redox environment for skeletal tissue regeneration.

Long Bone Mineral Loss, Bone Microstructural Changes and Oxidative Stress After Eimeria Challenge in Broilers

“…In vitro studies in human and mouse cells have shown that ROS is an important activator for various cell signaling pathways, mediated MSCs differentiation and cell fate ( Yang et al, 2013 ; Atashi et al, 2015 ). Accumulating evidence suggesting the alteration of the redox state causes systemic changes that can coordinate osteoblast differentiation or osteoclast activity that relat to the bone remodeling process in human and animal models ( Domazetovic et al, 2017 ; Schreurs et al, 2020 ; Sheppard et al, 2022 ). The supplementation of trace minerals can alleviate the negative effect of oxidative stress and optimize the bone quality in human and broilers ( Santos et al, 2020 ; Savaram Venkata et al, 2021 ).…”

Impact of exogenous hydrogen peroxide on osteogenic differentiation of broiler chicken compact bones derived mesenchymal stem cells

“…H 2 O 2 is well-known ROS signaling intermediate in response to tissue injury ( Sanchez-de-Diego et al, 2019 ). ROS activates signaling that influences vital pathways, such as Wnt or TGF/BMP pathways, which are response to fracture healing and tissue repairment mechanism by regulating osteogenic differentiation of stem cells ( Wang et al, 2017 ; Sheppard et al, 2022 ). MSCs can migrate to the sites of injury in response to various stimuli, including cytokines or growth factors, and differentiate into tissue-specific cell types to repair the damaged region ( Merimi et al, 2021 ).…”

The progress in titanium alloys used as biomedical implants: From the view of reactive oxygen species

“…Bone health and homeostasis are the result of a delicate balance between the activity of osteoblasts and osteoclasts. When maxillofacial bone suffers bone defect in response to periodontitis, trauma or tumor, cells such as osteocytes, osteoblasts and osteoclasts will are exposed to oxidative stress ( Sheppard et al, 2022 ). However, ROS may impede or undermine the complicated bone regeneration process through a variety of signaling pathways.…”