Direct, Broad-Spectrum Antimicrobial Activity of Ag+-Doped Hydroxyapatite against Fastidious Anaerobic Periodontal and Aerobic Dental Bacteria

Periodontitis and caries, while seemingly innocuous medical conditions, actually pose significant challenges because of their potential etiology with far more serious conditions. Efficacious treatment is hindered by bacterial antibiotic resistance. Standard AgNPs are ineffective against periodontal anaerobic bacteria, because they require oxidative dissolution to release Ag+ ions, which are the actual antimicrobial agents, but oxidation is not possible under anaerobic conditions. Prior studies on Ag-based periodontal antimicrobial materials either did not confirm a silver oxidation state or did not use strictly anaerobic growth media or both, causing spurious antimicrobial efficacy estimates. Here, we prove that silver ion-doped hydroxyapatite nanoparticles (AgHAp NPs) synthesized at various pHs contain an Ag+ oxidation state and directly release Ag+ even in a strictly anerobic medium. Thus, these AgHAp NPs exhibit direct antimicrobial activity against the fastidious anaerobic Gram-negative periodontal bacterium Fusobacterium nucleatum (F. nucleatum) and against caries-causing aerobic, Gram-positive bacterium Streptococcus mutans (S. mutans). The synthesis pH (6-11) correlates inversely with the Ag+ content (4.5-0.45 wt %) of AgHAp NPs and, hence, with antimicrobial efficacy, thus providing tunable efficacy for the target application. AgHAp NPs had greater antimicrobial efficacy than Ag-0-containing AgNPs and were less cytotoxic to the mouse fibroblast L929 cell line. Thus, AgHAp NPs (especially AgHAp7) are superior to AgNPs as effective, broad-spectrum, biocompatible antimicrobials against both anaerobic periodontal and aerobic dental bacteria. AgHAp NP synthesis is also inexpensive and scalable, which are significant factors for treating large global populations of indigent people affected by periodontitis and dental caries.