The effect of copper content in Ti-Cu alloy with bone regeneration ability on the phenotypic transformation of...

Titanium (Ti) alloys are widely used in bone repair due to their excellent biocompatibility and mechanical properties. However, managing post-implantation inflammatory responses in the defect region and accelerating the healing process remain major challenges in the design of such materials. As a bridge between the innate and adaptive immune systems, macrophages play a pivotal role in bone defect healing through their M2 polarization, which facilitates the secretion of tissue repair-promoting cytokines. Research on the role of copper ions (Cu²⁺) in regulating inflammatory responses at injury sites suggests their potential as active ions for incorporation into alloys as a secondary phase to modulate macrophage polarization. However, the effective concentration and mechanisms in this process remain unclear. Here, we synthesized Ti-xCu (x = 3, 5, 7 wt%) alloys and investigated the effects of copper concentration on macrophage M1/M2 polarization and the underlying mechanisms. In an 8-week rat mandibular bone regeneration experiment, Ti-5Cu demonstrated superior performance compared to pure titanium. At the early stage (2 weeks), Ti-5Cu promoted the dominance of M1 macrophages and upregulated inflammatory cytokines, facilitating the initial inflammatory response. Subsequently, a timely M1-to-M2 phenotype transition was observed, accompanied by elevated expression of the repair-related cytokine IL-10, ultimately leading to improved bone healing. This study provides a theoretical foundation for the development of titanium-copper composite materials with anti-inflammatory and pro-healing properties, paving the way for innovative solutions to promote bone defect repair.