Bone formation and bioresorption of silver-doped β-tricalcium phosphate in rabbit bone defects

Implant-associated infections pose a significant challenge in orthopedic surgery but may be prevented using biomaterials containing antimicrobial agents such as Ag ions. This study examines the effects of Ag doping on bone metabolism following the implantation of β-tricalcium phosphate (β-TCP) doped with 0, 1, 3, and 5 at% Ag with 75% porosity. Additionally, the antimicrobial activity of Ag-doped β-TCP was evaluated against <i>Staphylococcus aureus</i> and <i>Escherichia coli</i> using shake flask tests, revealing increased antimicrobial activity with higher Ag concentrations. Cylindrical bone defects (diameter 4 mm; depth 10 mm) were introduced in the lateral femoral condyles of rabbits and treated with Ag-doped β-TCP. The rabbits were euthanized at 2-, 4-, 8-, and 12-weeks post-operation (<i>n</i> = 6/time point). Specimens were decalcified for histological examination using optical and scanning electron microscopy (SEM). Bone formation, residual material, and tartrate-resistant acid phosphatase (TRAP)-positive cell counts were quantified, with statistical significance assessed using one-way ANOVA (<i>p</i> < 0.05). Bone formation increased over time up to 12 weeks but was lower with higher Ag concentrations. Residual material decreased, while TRAP-positive cells peaked at 2 weeks and gradually declined thereafter. SEM revealed Ag accumulation in the bone marrow outside the newly formed bone. Ag doping inhibited material resorption more than osteogenesis. Bone metabolism in the defect area was delayed as Ag concentration increased, likely due to reduced osteoclast activity. This study highlights the dual effect of Ag-doped β-TCP on bone metabolism and implant-associated infections. While Ag incorporation enhanced antimicrobial potential, higher concentrations delayed bone metabolism. Optimizing Ag content is crucial to balancing infection control with effective bone regeneration, guiding the development of advanced orthopedic implants.