title: Novel endodontic sealers induce cell cytotoxicity and apoptosis in a dose-dependent behavior and favorable response in mice subcutaneous tissue.
abstract: OBJECTIVE
  The objective of the present study is to evaluate the in vitro cytotoxicity and in vivo biocompatibility of two novel endodontic sealers: RealSeal XT1 and Sealapex Xpress on the subcutaneous connective tissue of mice.
  
  
  METHODS
  The cytotoxicity was assessed by cell viability using the MTT assay (one-way ANOVA), trypan blue test (Mann-Whitney) and cell apoptosis by flow cytometer. For the subcutaneous study, polyethylene tubes filled with the sealers were implanted in 70 BALB/c mice: 6 experimental groups (n = 10/group) and 2 control groups with empty tubes (n = 5/group). At the end of experimental periods (7, 21, and 63 days), the tissue was removed and histotechnically processed. Angioblastic proliferation and edema (Fisher's exact test) were evaluated, besides thickness measurement (μm) of the reactionary granulomatous tissue and neutrophil counts (Kruskal-Wallis and Dunn's post test; Mann-Whitney) (α = 0.05).
  
  
  RESULTS
  MTT assay, trypan blue, and analysis of apoptotic cells showed a dose-dependent direct effect: the more diluted the sealer, the less cytotoxic. Regarding the angioblastic proliferation and edema, difference between the sealers at 7 and 63 days occurred (p < 0.05). Both endodontic sealers initially promoted perimaterial tissue reaction as a foreign body granuloma and thus stimulated favorable tissue responses.
  
  
  CONCLUSIONS
  Both sealers showed a dose-dependent effect and promoted satisfactory subcutaneous tissue response; the sealer Sealapex Xpress was less cytotoxic and more biocompatible than RealSeal XT.
  
  
  CONCLUSIONS
  The step of root canal filling during endodontic treatment is highly important for the preservation of the periapical tissue integrity. Subcutaneous reaction to endodontic sealers enables scientific basis for clinical use.
authors.affiliation: Department of Pediatric Dentistry, School of Dentistry of Ribeirão Preto, University of São Paulo, Avenida do Café s/n, Monte Alegre, Ribeirão Preto, SP, 14040-904, Brazil.
authors.forename: L A B
authors.initials: LAB
authors.lastname: Silva
authors.affiliation: Department of Pediatric Dentistry, School of Dentistry of Ribeirão Preto, University of São Paulo, Avenida do Café s/n, Monte Alegre, Ribeirão Preto, SP, 14040-904, Brazil.
authors.forename: L U
authors.initials: LU
authors.lastname: Azevedo
authors.affiliation: Department of Oral Pathology, Bauru Dental School, University of São Paulo, Bauru, SP, Brazil.
authors.forename: A
authors.initials: A
authors.lastname: Consolaro
authors.affiliation: Department of Dental Medicine, Albert Einstein Medical Center, Philadelphia, PA, USA.
authors.forename: F
authors.initials: F
authors.lastname: Barnett
authors.affiliation: Department of Skeletal Biology, The Forsyth Institute, Cambridge, MA, USA.
authors.forename: Y
authors.initials: Y
authors.lastname: Xu
authors.affiliation: Department of Physical Medicine and Rehabilitation, University of Colorado School of Medicine, Denver, CO, USA.
authors.forename: R A
authors.initials: RA
authors.lastname: Battaglino
authors.affiliation: Department of Endodontics, School of Dentistry, University of Barcelona, Barcelona, Spain.
authors.forename: P S
authors.initials: PS
authors.lastname: Cañadas
authors.affiliation: Department of Pediatric Dentistry, School of Dentistry of Ribeirão Preto, University of São Paulo, Avenida do Café s/n, Monte Alegre, Ribeirão Preto, SP, 14040-904, Brazil. kmho@usp.br.
authors.forename: Katharina Morant Holanda
authors.initials: KMH
authors.lastname: de Oliveira
authors.affiliation: Department of Pediatric Dentistry, School of Dentistry of Ribeirão Preto, University of São Paulo, Avenida do Café s/n, Monte Alegre, Ribeirão Preto, SP, 14040-904, Brazil.
authors.forename: R A B
authors.initials: RAB
authors.lastname: Silva
mesh_terms: D000818:Animals; D017209:Apoptosis / Q000187:drug effects*; D001672:Biocompatible Materials / Q000494:pharmacology; D002126:Calcium Hydroxide / Q000494:pharmacology*; D049109:Cell Proliferation / Q000187:drug effects; D002470:Cell Survival / Q000187:drug effects; D003188:Composite Resins / Q000494:pharmacology*; D003603:Cytotoxins / Q000494:pharmacology*; D004305:Dose-Response Relationship, Drug; D005434:Flow Cytometry; D008422:Materials Testing; D051379:Mice; D012387:Root Canal Filling Materials / Q000494:pharmacology*; D012459:Salicylates / Q000494:pharmacology*; D040521:Subcutaneous Tissue / Q000187:drug effects*
chemical_list: D001672:Biocompatible Materials; D003188:Composite Resins; D003603:Cytotoxins; C511498:Real Seal composite resin; D012387:Root Canal Filling Materials; D012459:Salicylates; C055601:Sealapex; D002126:Calcium Hydroxide
keywords: Biocompatibility; Cell viability; Cytotoxicity; Endodontic sealers; Mice; Tissue response