title: Temporal-controlled Dexamethasone Releasing Chitosan Nanoparticle System Enhances Odontogenic Differentiation of Stem Cells from Apical Papilla.
abstract: BACKGROUND
  The spatial and temporal control of stem cell differentiation into odontoblast-like cells remains one of the major challenges in regenerative endodontic procedures. The current study aims to synthesize and compare the effect of dexamethasone (Dex) release from 2 variants of Dex-loaded chitosan nanoparticles (CSnp) on the odontogenic differentiation of stem cells from apical papilla (SCAP).
  
  
  METHODS
  Two variants of Dex-loaded CSnp were synthesized by encapsulation (Dex-CSnpI) and adsorption (Dex-CSnpII) methods. The physicochemical characterization of Dex-CSnpI and Dex-CSnpII was assessed by transmission electron microscopy, Zetasizer, and Fourier transform infrared spectroscopy, whereas the Dex release kinetics was assessed by spectrophotometry. A previously characterized SCAP cell line was cultured onto CSnp, Dex-CSnpI, or Dex-CSnpII. The biomineralization potential was determined by alizarin red staining. Alkaline phosphatase, dentin sialophosphoprotein, and dentin matrix protein-1 gene expressions were analyzed by real-time reverse-transcription polymerase chain reaction.
  
  
  RESULTS
  Dex-CSnpI resulted in slower release of Dex compared with Dex-CSnpII, but both demonstrated sustained release of Dex for 4 weeks. Biomineralization of SCAP was significantly higher (P < .05) in presence of Dex-CSnpII compared with that in Dex-CSnpI at 3 weeks. Alkaline phosphatase gene expression was significantly higher in the presence of Dex-CSnpII compared with Dex-CSnpI, with peak expression seen at 2 weeks (P < .05). The expression of odontogenic specific marker dentin matrix protein-1 was significantly higher in presence of Dex-CSnpII compared with Dex-CSnpI at 3 weeks (P < .05).
  
  
  CONCLUSIONS
  Collectively, these data suggest that sustained release of Dex results in enhanced odontogenic differentiation of SCAP. These findings highlight the potential of temporal-controlled delivery of bioactive molecules to direct the spatial- and temporal-controlled odontogenic differentiation of dental stem cells.
authors.affiliation: Discipline of Endodontics, Faculty of Dentistry, University of Toronto, Toronto, Ontario, Canada.
authors.forename: Suja
authors.initials: S
authors.lastname: Shrestha
authors.affiliation: Department of Endodontics, University of Texas Health Science Center at San Antonio, San Antonio, Texas.
authors.forename: Anibal
authors.initials: A
authors.lastname: Diogenes
authors.affiliation: Discipline of Endodontics, Faculty of Dentistry, University of Toronto, Toronto, Ontario, Canada. Electronic address: akishen@gmail.com.
authors.forename: Anil
authors.initials: A
authors.lastname: Kishen
mesh_terms: D000469:Alkaline Phosphatase / Q000378:metabolism; D000818:Animals; D002113:Calcification, Physiologic / Q000187:drug effects; D002454:Cell Differentiation / Q000187:drug effects* / Q000502:physiology; D002460:Cell Line; D002470:Cell Survival / Q000187:drug effects / Q000502:physiology; D048271:Chitosan / Q000737:chemistry; D003692:Delayed-Action Preparations / Q000138:chemical synthesis / Q000493:pharmacokinetics / Q000494:pharmacology; D003771:Dental Papilla / Q000166:cytology; D003907:Dexamethasone / Q000008:administration & dosage* / Q000138:chemical synthesis / Q000493:pharmacokinetics; D016326:Extracellular Matrix Proteins / Q000378:metabolism; D015870:Gene Expression / Q000187:drug effects; D006133:Growth Substances / Q000008:administration & dosage* / Q000138:chemical synthesis / Q000493:pharmacokinetics; D053758:Nanoparticles / Q000737:chemistry; D009805:Odontogenesis / Q000187:drug effects / Q000502:physiology; D010750:Phosphoproteins / Q000378:metabolism; D012795:Sialoglycoproteins / Q000378:metabolism; D013234:Stem Cells / Q000166:cytology / Q000187:drug effects* / Q000502:physiology; D000099311:Dentin Sialophosphoprotein
chemical_list: D000469:Alkaline Phosphatase; D048271:Chitosan; D003692:Delayed-Action Preparations; D003907:Dexamethasone; D016326:Extracellular Matrix Proteins; D006133:Growth Substances; D010750:Phosphoproteins; D012795:Sialoglycoproteins; D000099311:Dentin Sialophosphoprotein
keywords: Chitosan nanoparticles; dexamethasone; odontogenic differentiation; stem cells from the apical papilla; temporal-controlled release