Antimicrobial Effects of Novel Triple Antibiotic Paste-Mimic Scaffolds on Actinomyces naeslundii Biofilm.
BACKGROUND
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.
Division of Dental Biomaterials, Department of Restorative Dentistry, Indiana University School of Dentistry, Indianapolis, Indiana; Division of Nephrology, Indiana University School of Dentistry, Indianapolis, Indiana.
Maria T P
MT
Albuquerque
Division of Dental Biomaterials, Department of Restorative Dentistry, Indiana University School of Dentistry, Indianapolis, Indiana.
Stuart J
SJ
Ryan
Division of Dental Biomaterials, Department of Restorative Dentistry, Indiana University School of Dentistry, Indianapolis, Indiana; Department of Oral Biology, Indiana University School of Dentistry, Indianapolis, Indiana.
Eliseu A
EA
Münchow
Graduate Program in Restorative Dentistry (Endodontics), Universidade Estadual Paulista, São José dos Campos Dental School, São José dos Campos, São Paulo, Brazil.
Maria M
MM
Kamocka
Department of Operative Dentistry, Federal University of Pelotas (UFPEL), School of Dentistry, Pelotas, Rio Grande do Sul, Brazil.
Richard L
RL
Gregory
Division of Nephrology, Indiana University School of Dentistry, Indianapolis, Indiana.
Marcia C
MC
Valera
Division of Dental Biomaterials, Department of Restorative Dentistry, Indiana University School of Dentistry, Indianapolis, Indiana. Electronic address: mbottino@iu.edu.
Marco C
MC
Bottino
D000190:Actinomyces / Q000187:drug effects* / Q000502:physiology; D000196:Actinomycosis / Q000188:drug therapy* / Q000473:pathology / Q000503:physiopathology; D000900:Anti-Bacterial Agents / Q000008:administration & dosage* / Q000493:pharmacokinetics; D018441:Biofilms / Q000187:drug effects*; D002851:Chromatography, High Pressure Liquid; D002939:Ciprofloxacin / Q000008:administration & dosage / Q000493:pharmacokinetics; D003481:Cuspid / Q000187:drug effects / Q000473:pathology / Q000503:physiopathology; D003804:Dentin / Q000187:drug effects* / Q000382:microbiology* / Q000473:pathology / Q000503:physiopathology; D004338:Drug Combinations; D004353:Drug Evaluation, Preclinical; D065546:Drug Liberation; D006801:Humans; D008422:Materials Testing; D008795:Metronidazole / Q000008:administration & dosage / Q000493:pharmacokinetics; D008911:Minocycline / Q000008:administration & dosage / Q000493:pharmacokinetics; D057139:Nanofibers; D009824:Ointments; D016687:Polydioxanone; D014076:Tooth Diseases / Q000188:drug therapy* / Q000382:microbiology
D000900:Anti-Bacterial Agents; D004338:Drug Combinations; D009824:Ointments; D008795:Metronidazole; D016687:Polydioxanone; D002939:Ciprofloxacin; D008911:Minocycline
Antibiotic; bacteria; disinfection; electrospinning; nanofibers; pulp; regeneration; root canal; scaffold; stem cells