Low Percent Copper Doping Limits Bacterial Adhesion on Fluorapatite-Based Bone Scaffolds

Natural and engineered bone grafts are widely used in orthopedic and dental reconstruction; however, infection remains a persistent clinical challenge. Fluorapatite (FAp) is a chemically stable and osteoconductive bone substitute, but it lacks inherent antimicrobial properties. Copper (Cu), known for its potent antibacterial activity, could be incorporated into the FAp crystal structure, yet studies on Cu-doped fluorapatite (CuFAp) are limited. Notably, our previous research demonstrated that Cu doping at 1-5 mol% concentrations generated surfaces that inhibited bacterial adhesion, but were also cytotoxic to osteoblasts, suggesting that even lower concentrations could promote osteoblast activity while preventing bacterial adhesion. Therefore, we hypothesized that doping FAp with low Cu concentrations (0.25, 0.50, 0.75, and 1.0 mol%) would result in a significant reduction in bacterial adhesion while preserving osteogenic properties. Material characterization analyses confirmed successful Cu substitution at these levels within the apatite lattice without the formation of secondary oxide phases. Surface analysis of sintered CuFAp surfaces revealed an increase in grain sizes with increasing Cu contents. Antibacterial assays using Staphylococcus aureus and Pseudomonas aeruginosa demonstrated that 0.25-0.50 mol% CuFAp reduced bacterial adhesion on their surface by up to 3 log-fold compared to undoped FAp. Crucially, osteoblast viability remained unaffected over 72 h (p > 0.05). Based on these results, 0.50 mol% CuFAp scaffolds were evaluated in a pilot rat model of contaminated critical-size bone defects. Histological assessment confirmed complete bone regeneration with minimal inflammation, highlighting both osteogenic and antibacterial adhesion properties of these surfaces. Collectively, these findings indicate that low-concentration CuFAp scaffolds represent a promising biomaterial for infection-resistant bone defect repair.