Templated Synthesis of Hollow RuO2 Nanospheres for Alleviating Metal Wear Particle‐Induced Osteoclast Activation and Bone Loss

Abstract Wear particulate debris‐induced osteoclast over‐activation is a major causative factor in periprosthetic osteolysis and aseptic loosening, resulting in the non‐infectious failure of total joint arthroplasty. To mitigate such pathological bone loss, various therapeutic targets have been identified. Oxidative stress is one of the main contributing factors in the promotion of osteoclastogenesis. Herein, using a template‐assisted approach, hollow ruthenium oxide (RuO 2 ) nanospheres are synthesized as an effective antioxidant for the treatment of CoCrMo alloy particles‐induced osteolysis. Hollow RuO 2 significantly suppressed receptor activator of nuclear factor kappa‐B ligand (RANKL)‐induced osteoclastogenesis, bone resorption, and the expression of specific markers (including NFATc1, c‐Fos, MMP9, CTSK, and DC‐STAMP) of bone marrow‐derived macrophages via inhibition of the nuclear factor kappa‐B (NF‐κB) and tumor necrosis factor (TNF)‐α pathways. In mouse calvaria, hollow RuO 2 nanozymes demonstrate an appreciable attenuation in osteoclast differentiation, bone loss, and soft tissue malformations induced by CoCrMo alloy particles. This study envisions that the antioxidant nanozymes may be further applied as a therapeutic entity in the prevention and treatment of other inflammatory and oxidative stress‐related ailments.