A nanoengineered coating with dual antioxidant and immunomodulatory functions on titanium implants for osteoregeneration in osteoporosis

Abstract

Poor implant-bone integration under osteoporotic conditions remains a critical clinical challenge. The osteoporotic microenvironment, characterized by excessive oxidative stress, immune homeostasis imbalance, and persistent chronic inflammation, significantly impedes bone regeneration. To address this issue, we fabricated a multifunctional bioactive coating on the surface of Ti implants, integrating antioxidant, immunomodulatory, and osteogenic properties. In this study, we synthesized an in-situ lanthanum oxide (La₂O₃) nanoparticle coating (denoted as AT/La₂O₃) on the surface of titanium implants using hydrothermal and high-temperature calcination techniques. Subsequently, regaloside A (RA), a bioactive compound with therapeutic potential, was loaded onto the coating via an impregnation method to obtain AT/La₂O₃/RA. The composite coating demonstrated sustained and stable release of both RA and La³⁺ ions. Meanwhile, AT/La₂O₃/RA exhibited good reactive oxygen species (ROS) scavenging capability. Furthermore, it significantly promoted macrophage polarization toward the M2 phenotype, upregulating anti-inflammatory cytokines (IL-4RA and IL-10) while downregulating pro-inflammatory mediators (TNF-α and MMP2), thereby mitigating chronic inflammation. In addition, the coating markedly enhanced the proliferation and osteogenic differentiation of MSCs. Furthermore, in vivo evaluations showed that AT/La₂O₃/RA could effectively attenuated oxidative stress and suppressed inflammatory responses, ultimately fostering robust osseointegration. These findings highlight the potential of AT/La₂O₃/RA as a promising surface modification strategy to improve implant performance in the clinics.