Abstract
Background: Tantalum (Ta) and its derivatives are inert, possess mechanical qualities such as corrosion resistance, and are biocompatible. They also offer structural support during surgical correction, such as bone grafts during surgery, in instances of dental or skeletal disabilities. However, various sizes of Ta particles could be expelled from the implant's surface due to mechanical stress and load-induced wear caused by micromotion between loose implant surfaces during usage. Therefore, the study examined the effects of nano (25 nm) and micro-sized Ta particles (10 μm and 40-50 μm) on osteoblasts and osteoclasts. Results: Osteoblasts efficiently phagocytosed 25 nm sized Ta particles compared to micro-sized particles and triggered significant biological effects. Only 25 nm Ta particles suppressed ALP activity, downregulated osteogenic regulators and markers, and inhibited collagen synthesis and mineralization. Moreover, 25 nm sized Ta particles induced inflammatory responses in osteoblasts by increasing Cox-2 expression and activating the NFkB signaling pathway. Nano-sized Ta particles induced intracellular ROS generation in osteoblasts and osteoclasts. Compared to micro-sized Ta particles, 25 nm sized Ta particles stimulated osteoclast formation, but ROS scavenging by N-acetyl cysteine (NAC) inhibited Ta particle-mediated osteoclastogenesis. Likewise, ALP activity of osteoblasts was partially restored after NAC treatment. 25 nm Ta particles suppressed Axin-2 reporter activity and protein levels of pGSK3β and β-catenin stability, implicating suppressed WNT signaling in treated osteoblasts. Expression levels of several families of antagonists like DKK, sFRP, and SOST of the WNT signaling pathway were found elevated several-fold in 25 nm-sized Ta particles treated osteoblasts, explaining suppressed WNT signaling pathway in exposed osteoblasts. Conclusion: Ta supports osseointegration and biocompatibility, but micromotion-induced nanoscale wear particles may disrupt osteoprogenitor function and enhance osteoclast activity, risking implant loosening. Thus, vigilant post-operative monitoring for nano-sized Ta particles is advisable and critical in detecting early osteolysis and ensuring implant longevity.