Synthesis of Antibacterial Monomers and Incorporation into Caries-Inhibiting Calcium-Phosphate Nanocomposite

Composites are the principal material for tooth cavity restorations due to their esthetics and direct-filling capabilities.  However, composites accumulate biofilms in vivo, and secondary caries due to biofilm acids is the main cause of restoration failure.   Objectives: (1) Synthesize new antibacterial monomers and (2) Develop nanocomposite containing nanoparticles of amorphous calcium phosphate (NACP) and new antibacterial monomer.  Methods: Two new antibacterial monomers were synthesized: dimethylaminohexyl methacrylate (DMAHM) with a carbon chain length of 6, and dimethylaminododecyl methacrylate (DMADM) with a chain length of 12.  A spray-drying technique was used to make NACP.  DMADM was incorporated into NACP nanocomposite at mass fractions of 0%, 0.75%, 1.5%, 2.25% and 3%.  A dental plaque microcosm biofilm model with human saliva as inoculum measured the viability, metabolic activity, and lactic acid production of biofilms on composites.  Results: Minimum inhibitory concentration (MIC) and bactericidal concentration (MBC) measurements indicated that DMAHM was more potent than quaternary ammonium dimethacrylate (QADM).  MIC and MBC of DMADM were 2-3 orders of magnitude lower than those of DMAHM, and approached those of chlorhexidine control.  At each DMADM mass fraction, DMADM-NACP nanocomposites had strengths similar to that of composite control (69±8)MPa (p>0.1).  With 3% DMADM in NACP nanocomposite, the metabolic activity of adherent biofilms was (0.11±0.02), which represents a 95% reduction compared to composite control (p<0.05).  Lactic acid production by biofilms on NACP nanocomposite containing 3% DMADM was (0.22±0.08)mmol/L, which represents a 99% reduction compared to composite control (p<0.05).  Biofilm colony-forming units on NACP nanocomposite with 3% DMADM were reduced by 2-3 orders of magnitude (p<0.05).  Conclusions: New antibacterial monomers were synthesized, and the carbon chain length had a strong effect on antibacterial efficacy.  The new DMADM-NACP nanocomposite possessed potent anti-biofilm activity without compromising load-bearing properties, and is promising for antibacterial and remineralizing dental restorations to inhibit secondary caries.