@article{Ma2026, 
author = {Yan Ma and Yufei Liu and Pan Chen and Yingfeng Su and Zizheng Chen and Xiangqian Fang and Yujun Zhang and Junxin Chen and Wenbin Xu},
title = {Bioinspired cascade nanozymes reprogram osteoarthritic joints: Mn-Nb2C-CeO2 mediated immuno-redox circuitry for self-healing cartilage},
year = {2026},
journal = {Nano Research},
volume = {19},
number = {1},
pages = {94908293},
keywords = {osteoarthritis, nitrogen doping, bioinspired nanozymes, immuno-redox circuitry, cartilage reprogramming, MXene hydrogels},
url = {https://www.sciopen.com/article/10.26599/NR.2025.94908293},
doi = {10.26599/NR.2025.94908293},
abstract = {Osteoarthritis (OA), a debilitating joint disorder affecting millions worldwide, is characterized by persistent inflammation, oxidative stress, and irreversible cartilage breakdown, yet remains without disease-modifying therapies. Inspired by natural enzymatic cascades, we developed a bioinspired nanocomposite hydrogel, N,S-doped Mn-Nb (C-CeO), that mimics endogenous antioxidant pathways to reprogram the OA microenvironment. This system combines N,S-doped Mn-Nb2C MXene nanosheets with CeO2 nanozymes within a boronate ester-crosslinked hydrogel, forming an “immuno-redox circuitry” with four synergistic functions: (1) cascade reactive oxygen species (ROS) scavenging via superoxide dismutase-like Mn-Nb2C and catalase-like CeO2, amplified by photothermal enhancement under near-infrared irradiation; (2) broad reactive nitrogen species clearance, removing peroxynitrite (ONOO−), nitric oxide (NO), and nitroxyl (NO−) to mitigate inflammation; (3) immunomodulation through Mn2+-activated cGAS-STING signaling, which promoted macrophage polarization toward the M2 phenotype, concomitantly reducing the levels of pro-inflammatory cytokines such as interleukin-1 beta (IL-1β) and tumor necrosis factor-alpha (TNF-α); (4) cartilage regeneration via pH/ROS-responsive simvastatin (SIM) release and nanocatalysis, upregulating SRY-box transcription factor 9 (SOX9) and Col2a1 while inhibiting matrix metalloproteinase-13 (MMP-13) and a disintegrin and metalloproteinase with thrombospondin motifs 5 (ADAMTS5). In a murine OA model, the system reduced synovitis by 60%, restored 80% of cartilage thickness, and suppressed osteophyte formation, outperforming single-component treatments. This strategy pioneers a “self-healing cartilage” approach by integrating nanocatalysis with immunoengineering for transformative OA therapy.}
}