title: Dental pulp stem cell responses to novel antibiotic-containing scaffolds for regenerative endodontics.
abstract: OBJECTIVE
  To evaluate both the drug-release profile and the effects on human dental pulp stem cells' (hDPSC) proliferation and viability of novel bi-mix antibiotic-containing scaffolds intended for use as a drug delivery system for root canal disinfection prior to regenerative endodontics.
  
  
  METHODS
  Polydioxanone (PDS)-based fibrous scaffolds containing both metronidazole (MET) and ciprofloxacin (CIP) at selected ratios were synthesized via electrospinning. Fibre diameter was evaluated based on scanning electron microscopy (SEM) images. Pure PDS scaffolds and a saturated CIP/MET solution (i.e. 50 mg of each antibiotic in 1 mL) (hereafter referred to as DAP) served as both negative (nontoxic) and positive (toxic) controls, respectively. High-performance liquid chromatography (HPLC) was performed to investigate the amount of drug(s) released from the scaffolds. WST-1(®) proliferation assay was used to evaluate the effect of the scaffolds on cell proliferation. LIVE/DEAD(®) assay was used to qualitatively assess cell viability. Data obtained from drug release and proliferation assays were statistically analysed at the 5% significance level.
  
  
  RESULTS
  A burst release of CIP and MET was noted within the first 24 h, followed by a sustained maintenance of the drug(s) concentration for 14 days. A concentration-dependent trend was noticed upon hDPSCs' exposure to all CIP-containing scaffolds, where increasing the CIP concentration resulted in reduced cell proliferation (P < 0.05) and viability. In groups exposed to pure MET or pure PDS scaffolds, no changes in proliferation were observed.
  
  
  CONCLUSIONS
  Synthesized antibiotic-containing scaffolds had significantly lower effects on hDPSCs proliferation when compared to the saturated CIP/MET solution (DAP).
authors.affiliation: Department of Restorative Dentistry, Division of Dental Biomaterials, Indiana University School of Dentistry (IUSD), Indianapolis, IN, USA.
authors.forename: K
authors.initials: K
authors.lastname: Kamocki
authors.affiliation: Department of Cariology, Restorative Sciences and Endodontics, University of Michigan School of Dentistry, Ann Arbor, MI, USA.
authors.forename: J E
authors.initials: JE
authors.lastname: Nör
authors.affiliation: Department of Restorative Dentistry, Division of Dental Biomaterials, Indiana University School of Dentistry (IUSD), Indianapolis, IN, USA.
authors.forename: M C
authors.initials: MC
authors.lastname: Bottino
mesh_terms: D000900:Anti-Bacterial Agents / Q000008:administration & dosage*; D000890:Anti-Infective Agents / Q000008:administration & dosage*; D002470:Cell Survival / Q000187:drug effects; D002851:Chromatography, High Pressure Liquid; D002939:Ciprofloxacin / Q000008:administration & dosage*; D003782:Dental Pulp / Q000166:cytology*; D004203:Disinfection / Q000379:methods*; D016503:Drug Delivery Systems; D006801:Humans; D008422:Materials Testing; D008795:Metronidazole / Q000008:administration & dosage*; D008855:Microscopy, Electron, Scanning; D016687:Polydioxanone / Q000737:chemistry; D012390:Root Canal Therapy; D013234:Stem Cells / Q000187:drug effects*; D054457:Tissue Scaffolds / Q000737:chemistry*
chemical_list: D000900:Anti-Bacterial Agents; D000890:Anti-Infective Agents; D008795:Metronidazole; D016687:Polydioxanone; D002939:Ciprofloxacin
keywords: antibiotic pastes; drug delivery; nanofibres; regeneration; root canal; stem cells