3D bioprinted nanozyme-enhanced GelMA hydrogel with antioxidant/anti-inflammatory potential for bone repair

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 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. <em>In vitro</em> 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 40kDa (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.