Valence state of cerium oxide nanoparticles manipulate the fate of macrophages and mesenchymal stem cells and subsequent bone formation

Statement of Purpose: Understanding the interactions between stem cells and biomaterials surface is essential for controlling stem cell fates. Despite that tremendous advancements have been made in tailoring bone biomaterials to modulate stem cell fates, identification of the influences of specific surface features of biomaterials on stem cell functions remains difficult. Macrophages play a critical role in host reactions in the early stage of bone biomaterial insertion, and their initial response to a biomaterial can determine the success of biomaterial-associated osteogenesis [1]. The prohealing M2-polarized macrophage phenotype can elicit positive outcomes on osteogenesis, angiogenesis, and osseointegration [2, 3]. The mixed valence state of cerium oxide nanoparticles (CeONPs) has therapeutic potential due to the possibility of scavenging ROS in cells [4, 5]. For example, CeONPs supplied to murine J774A.1 macrophage can scavenge ROS and inhibit inflammatory mediator production. In this study, CeONPs were applied at different Ce⁴⁺/Ce³⁺ ratios to titanium substrate surface to modulate macrophage behavior, thereby promoting new bone formation.