Antimicrobial Effects of Novel Triple Antibiotic Paste-Mimic Scaffolds on Actinomyces naeslundii Biofilm

J Endod. 2015 Aug;41(8):1337-43. doi: 10.1016/j.joen.2015.03.005. Epub 2015 Apr 25.

Abstract

Introduction: Actinomyces naeslundii has been recovered from traumatized permanent teeth diagnosed with necrotic pulps. In this work, a triple antibiotic paste (TAP)-mimic scaffold is proposed as a drug-delivery strategy to eliminate A. naeslundii dentin biofilm.

Methods: Metronidazole, ciprofloxacin, and minocycline were added to a polydioxanone (PDS) polymer solution and spun into fibrous scaffolds. Fiber morphology, mechanical properties, and drug release were investigated by using scanning electron microscopy, microtensile testing, and high-performance liquid chromatography, respectively. Human dentin specimens (4 × 4 × 1 mm(3), n = 4/group) were inoculated with A. naeslundii (ATCC 43146) for 7 days for biofilm formation. The infected dentin specimens were exposed to TAP-mimic scaffolds, TAP solution (positive control), and pure PDS (drug-free scaffold). Dentin infected (7-day biofilm) specimens were used for comparison (negative control). Confocal laser scanning microscopy was done to determine bacterial viability.

Results: Scaffolds displayed a submicron mean fiber diameter (PDS = 689 ± 312 nm and TAP-mimic = 718 ± 125 nm). Overall, TAP-mimic scaffolds showed significantly (P ≤ .040) lower mechanical properties than PDS. Within the first 24 hours, a burst release for all drugs was seen. A sustained maintenance of metronidazole and ciprofloxacin was observed over 4 weeks, but not for minocycline. Confocal laser scanning microscopy demonstrated complete elimination of all viable bacteria exposed to the TAP solution. Meanwhile, TAP-mimic scaffolds led to a significant (P < .05) reduction in the percentage of viable bacteria compared with the negative control and PDS.

Conclusions: Our findings suggest that TAP-mimic scaffolds hold significant potential in the eradication/elimination of bacterial biofilm, a critical step in regenerative endodontics.

Keywords: Antibiotic; bacteria; disinfection; electrospinning; nanofibers; pulp; regeneration; root canal; scaffold; stem cells.

Publication types

  • Research Support, N.I.H., Extramural
  • Research Support, Non-U.S. Gov't

MeSH terms

  • Actinomyces / drug effects*
  • Actinomyces / physiology
  • Actinomycosis / drug therapy*
  • Actinomycosis / pathology
  • Actinomycosis / physiopathology
  • Anti-Bacterial Agents / administration & dosage*
  • Anti-Bacterial Agents / pharmacokinetics
  • Biofilms / drug effects*
  • Chromatography, High Pressure Liquid
  • Ciprofloxacin / administration & dosage
  • Ciprofloxacin / pharmacokinetics
  • Cuspid / drug effects
  • Cuspid / pathology
  • Cuspid / physiopathology
  • Dentin / drug effects*
  • Dentin / microbiology*
  • Dentin / pathology
  • Dentin / physiopathology
  • Drug Combinations
  • Drug Evaluation, Preclinical
  • Drug Liberation
  • Humans
  • Materials Testing
  • Metronidazole / administration & dosage
  • Metronidazole / pharmacokinetics
  • Minocycline / administration & dosage
  • Minocycline / pharmacokinetics
  • Nanofibers
  • Ointments
  • Polydioxanone
  • Tooth Diseases / drug therapy*
  • Tooth Diseases / microbiology

Substances

  • Anti-Bacterial Agents
  • Drug Combinations
  • Ointments
  • Metronidazole
  • Polydioxanone
  • Ciprofloxacin
  • Minocycline