Antioxidant-Thermoresponsive Collagen/Chitosan Nanocomposite Hydrogels With Praseodymium-Doped Mesoporous Bioglass for Enhanced Bone Regeneration.

Abstract

Oxidative stress is a critical barrier to effective bone regeneration, often impairing cellular function and osteogenic differentiation. In this study, we report the novel development of a multifunctional chitosan/collagen (CS/Coll) hydrogel integrated with praseodymium-doped mesoporous bioactive glass nanoparticles (Pr-MBGNs) engineered for the first time to simultaneously scavenge reactive oxygen species (ROS) and promote osteogenesis. The antioxidant potential of the Pr-MBGNs-loaded hydrogels was confirmed through hydrogen peroxide (H₂O₂) scavenging assays, demonstrating over 98% H₂O₂ reduction at optimal concentrations with significant reduction in intracellular ROS production. Under oxidative stress conditions, the hydrogels significantly restored rMSC viability, enhanced cell adhesion, and supported sustained proliferation. Mechanically, the incorporation of Pr-MBGNs modulated hydrogel crosslink density and stiffness, which favor improved cell-material interactions. Osteogenic assays showed a significant upregulation of key osteogenic markers (RUNX2, OCN, and OSX) and increase in matrix mineralization over 28 days. These outcomes are attributed to the synergistic effect of antioxidant protection and sustained release of bioactive ions from the Pr-MBGNs, which reprogrammed the redox environment and enhanced the osteoinductive microenvironment. Collectively, this study presents a first-of-its-kind nanoengineered hydrogel system that integrates ROS scavenging and osteogenic stimulation, offering a promising biomimetic strategy for bone tissue engineering in oxidative stress-related pathological conditions.