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Research Progress

Bioinspired artificial antioxidases for redox homeostasis and bone regeneration

发布时间： 2025-06-17 09:39 点击：27

Maxillofacial bone defects that include the maxilla and mandible arising from degenerative diseases, trauma, congenital anomalies, or tumors can lead to significant functional impairments and significantly diminish patients' life quality, which affects about 2 million patients all over the world. Although stem cell-based therapy offers the promise of reconstruction large and inflammatory maxillofacial defects, the field has long faced a thorny problem: high levels of reactive oxygen species (ROS), hypoxia, and intense inflammation in areas of inflammatory defects constitute an ‘adverse microenvironment’ that is not conducive to stem cell survival and function.

“Conventional ROS-scavenging artificial antioxidases have obvious limitations,” explained Chong Cheng, professor and head of the Advanced Low-Dimensional Materials Group at Sichuan University. “Existing artificial antioxidases exhibit sluggish enzymatic reaction rates due to the deficiency of proton/electron transfer within the active centers. Moreover, the susceptibility of biocatalytic centers to ROS-induced poisoning hampers the long-term ROS elimination activity due to challenges in creating high electron density and achieving fast electron recovery.”

In bioorganisms, natural enzymes usually do not operate independently, but rather, a series of enzymes participate in the same biological process. Professor Cheng further explains, “The intracellular antioxidant defense systems (IADS) require the collaborative efforts of glutathione peroxidase (GPx), superoxide dismutase (SOD), catalase (CAT), and others to uphold the cellular redox balance. The effective ROS elimination by the IADS involves rapid proton and electron transfer processes and also hydrogen contained substrates or coenzymes.”

Recently, to mimic this natural IADS mechanism for efficient redox reactions, Professor Cheng's team published a breakthrough study in Nature Communications ("Bioinspired artificial antioxidases for efficient redox homeostasis and maxillofacial bone regeneration"). They proposed the de novo bioinspired design of an efficient artificial antioxidase via using Ru-doped layered double hydroxide (named Ru-hydroxide) for superior redox homeostasis and maxillofacial bone regeneration.

The research team found that the Ru catalytic sites in Ru-hydroxide can react with oxygen species efficiently and cooperate with hydroxyls to complete rapid proton and electron transfer, thus significantly reducing the activation energy of antioxidative reactions. Accordingly, the Ru-hydroxide exhibits efficient and simultaneous SOD-, CAT-, and GPx-mimetic activities for ROS elimination, as well as favourable cycling stability for long-term usage.

Bioinspired design of artificial antioxidases and therapeutic effects in treating inflammatory maxillofacial bone defects. a Illustration of the bioinspired design of Ru-hydroxide with rapid and sustained protons/electrons transfer functions, and b it serves as the antioxidase-like biocatalytic materials for protecting endogenous stem cells and promoting inflammatory mandible regeneration. (Image reprinted from DOI:10.1038/s41467-025-56179-0, CC BY) (click on image to enlarge)

In cellular experiments, Ru-hydroxide demonstrates the antioxidase-like ability to sustain stem cell viability and promote osteoblastic differentiation under conditions of elevated ROS. Ting Wang, the first author and a doctoral student in Cheng's team, noted, “These biomimetic artificial antioxidases effectively mitigate oxidative stress-mediated DNA damage and cellular apoptosis, thus supporting critical metabolic pathways, developmental cascades, and osteogenic functionality while attenuating pro-inflammatory signaling mechanisms.”

The research team validated the efficacy of Ru-hydroxide in an animal model by applying it to repair mandibular defects in rats. Rats treated with Ru-hydroxide demonstrated significant inflammatory mandibular regeneration compared to the control group. In addition, Ru-hydroxide was also found to create “no obvious difference in the biochemical indices of liver and kidney functions and no noticeable damage or abnormalities for the major organ tissues, including heart, lung, liver, kidney, and spleen”.

Although further studies are needed before entering human clinical trials, the research team is confident in the potential of Ru-hydroxide. Professor Cheng concludes, “The synthesized Ru-hydroxide exhibits efficient in vivo biocatalytic microenvironment modulation during inflammatory bone tissue regeneration, providing a hopeful avenue for developing antioxidase-like biomaterials to treat a broad range of inflammation-associated diseases, such as arthritis, diabetic wounds, enteritis, and bone fractures.”