Glutathione-coated titanium implants promote bone defect repair through antioxidant stress

Abstract

Elevated levels of reactive oxygen species (ROS) in the bone defect area impede bone regeneration and repair. Although titanium and its alloys are widely used for bone defect repair, they lack bioactivity and the ability to scavenge ROS at the defect site, leading to poor osseointegration. To address this, surface modification of Ti alloys with coatings is a common strategy. This study aimed to investigate the osteogenic and antioxidant effects of a novel glutathione (GSH)-coated Ti screw (Ti^GSH) on bone regeneration. Ti^GSH was fabricated using a PDA intermediary layer, followed by chelation with GSH. In vitro studies demonstrated sustained GSH release from Ti^GSH over 15 days. In vivo studies revealed that Ti^GSH did not alter the levels of GSH in the plasma of rats, but it significantly increased the GSH content at the bone defect site. Ti^GSH effectively scavenged DPPH• radicals and reduced intracellular ROS levels in bone marrow mesenchymal stem cells (BMSCs), promoting their proliferation, osteogenic differentiation, and mineralization. In vivo experiments in a rat bone defect model showed that Ti^GSH significantly reduced the level of oxidative stress at the bone defect site, thereby enhancing the bone regeneration and osseointegration capabilities of the titanium screw. Meanwhile, Ti^GSH did not cause any adverse effects in the rats. Overall, Ti^GSH demonstrates promising potential as a biocompatible and osteoinductive material for bone defect repair, with sustained local GSH release mitigating oxidative stress and promoting bone regeneration.