Functionalized TiCu/TiCuN coating promotes osteoporotic fracture healing by upregulating the Wnt/β-catenin pathway

Abstract

Osteoporosis results in decreased bone mass and insufficient osteogenic function. Existing titanium alloy implants have insufficient osteoinductivity and delayed/incomplete fracture union can occur when used to treat osteoporotic fractures. Copper ions have good osteogenic activity, but their dose-dependent cytotoxicity limits their clinical use for bone implants. In this study, titanium alloy implants functionalized with a TiCu/TiCuN coating by arc ion plating achieved a controlled release of copper ions in vitro for 28 days. The coated alloy was co-cultured with bone marrow mesenchymal stem cells and showed excellent biocompatibility and osteoinductivity in vitro. A further exploration of the underlying mechanism by quantitative real-time polymerase chain reaction and western blotting revealed that the enhancement effects are related to the upregulation of genes and proteins (such as axin2, β-catenin, GSK-3β, p-GSK-3β, LEF1, and TCF1/TCF7) involved in the Wnt/β-catenin pathway. In vivo experiments showed that the TiCu/TiCuN coating significantly promoted osteoporotic fracture healing in a rat-femur fracture model, and has good in vivo biocompatibility based on various staining results. Our study confirmed that TiCu/TiCuN-coated Ti promotes osteoporotic fracture healing associated with the Wnt pathway. Because the coating effectively accelerates the healing of osteoporotic fractures and improves bone quality, it has significant clinical application prospects.

Carnosine, Zinc and Copper: A Menage a Trois in Bone and Cartilage Protection

“…Several studies ascribe its antimicrobial activity to the increased Cu 2+ ions uptake into bacteria, where Cu causes oxidative stress with consequent damage of cytoplasmic membrane and DNA, and suggest its use in implant materials to prevent infections [170,171]. In addition, the osteogenic activity of Cu has been associated with the regulation of the Wnt/β-catenin signaling [172]. This pathway stimulates the osteogenic differentiation of BMSCs and plays an essential role in controlling bone remodeling [173].…”

“…Therefore, Wnt/β-catenin signaling has been proposed as a potential therapeutic target for the treatment of osteoporosis [175]. As shown by Tan et al, Cu 2+ ions released by titanium alloy implants upregulated genes and proteins involved in the Wnt signaling, including axin2, β-catenin, glycogen synthase kinase 3 (GSK-3β), LEF1 and TCF1/TCF7, and promoted osteoporotic fracture healing in vivo [172]. However, excessive Cu concentration exerted an inhibitory effect on the Wnt pathway in fish embryos, suggesting that the stimulatory effect of Cu on bone regeneration could be associated with its activity on the Wnt/β-catenin axis [172].…”

Fibrous topology promoted pBMP2-activated matrix on titanium implants boost osseointegration

“…In addition to focusing on the promotion of osteogenic activity by surface modifications, the problem of bacterial infection should not be overlooked. Infections at the implant interface can lead to implant loosening and detachment [ 22 , 23 ]. While designing surfaces with antimicrobial capabilities is essential, some antibacterial agents may inhibit osteoblast cell growth or interfere with effective biochemical molecules.…”