The repair of large-scale bone defects is still a challenge in clinical orthopedics. Especially, excessive reactive oxygen species (ROS)-induced oxidative stress injury greatly affected bone healing. In this study, we innovatively developed an antioxidant three-dimensional (3D)-bioprinted M-Mn3O4@Gel by integrating M-Mn3O4 nanozyme into photo-crosslinked gelatin methacryloyl (GelMA) for the therapy of bone defects. Results showed that the incorporation of M-Mn3O4 not only enhanced the mechanical properties of the nanocomposite hydrogel with the compressive modulus 141.79% higher than that of pure GelMA, but also maintained excellent 3D printability. In vitro studies confirmed that the 3D-printed M-Mn3O4@Gel exhibited favorable biocompatibility and cell adhesion. It significantly reduced oxidative stress through efficient ROS scavenging, restored mitochondrial function, and ultimately demonstrated remarkable osteogenic capacity, highlighting the efficacy of control-released nanozymes. More importantly, under near-infrared (NIR) irradiation, M-Mn3O4@Gel demonstrated further enhanced ROS-scavenging capacity and bone regeneration potential. Mechanistically, M-Mn3O4@Gel promoted osteogenesis by upregulating heat shock protein 40 kDa (HSP40) and HSP70 expression, effectively mitigating the overactivation of the Nrf2 pathway. This study innovatively combines nanozyme technology with 3D-printed hydrogel materials, offering a novel strategy to address the challenge of oxidative stress in bone regeneration.
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Open Access
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Nano Research 2025, 18(10): 94907979
Published: 28 September 2025
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