title: Osteogenic and Angiogenic Response to Calcium Silicate-based Endodontic Sealers.
abstract: BACKGROUND
  Calcium silicate-based endodontic sealers are reported to favor the regeneration of periradicular tissues, a process requiring concerted osteogenic and angiogenic events. This study compared 4 calcium silicate-based sealers for the effects of their extracts on osteogenic and angiogenic cell behavior.
  
  
  METHODS
  Extracts from ProRoot MTA (Dentsply Tulsa Dental, Tulsa, OK), MTA Plus (Prevest Denpro Limited, Jammu City, India), MTA Fillapex (Angelus, Londrina, PR, Brazil), and Biodentine (Septodont, Saint-Maur-des-Fosses, France) were prepared from freshly mixed sealers (0.1 g/cm(2)/mL extraction medium) and diluted (1:2-1:20). The sealers were compared for the dose- and time-dependent effects on the proliferation and differentiation of human mesenchymal stem cells (hMSCs) and human umbilical vein endothelial cells (HUVECs). An ex vivo osteogenic assay (regeneration of neonatal mice parietal bone defects) and an in vivo angiogenesis assay (chorioallantoic membrane assay) were performed.
  
  
  RESULTS
  Diluted extracts from MTA ProRoot and MTA Plus had evident stimulatory effects on the proliferation of hMSCs, alkaline phosphatase activity, and ex vivo regeneration of bone defects. They also increased HUVEC growth; allowed normal tubularlike network organization; and, in vivo, did not affect angiogenesis. Comparatively, Biodentine also elicited a favorable response on hMSCs and HUVECs, but the overall osteogenic and angiogenic outcome was slightly lower. MTA Fillapex exhibited the highest toxicity in hMSCs and HUVECs and, unlike the other sealers, only allowed a partial regeneration of bone defects.
  
  
  CONCLUSIONS
  The sealers caused dose- and time-dependent effects on the osteoblastic and endothelial response, eliciting similar cytocompatibility profiles. Results suggest that the induction of both osteogenic and angiogenic events may contribute to the sealers' regenerative outcome.
authors.affiliation: Laboratory for Bone Metabolism and Regeneration, Faculty of Dental Medicine, Universidade do Porto, Porto, Portugal.
authors.forename: Fábio
authors.initials: F
authors.lastname: Costa
authors.affiliation: Laboratory for Bone Metabolism and Regeneration, Faculty of Dental Medicine, Universidade do Porto, Porto, Portugal.
authors.forename: Pedro
authors.initials: P
authors.lastname: Sousa Gomes
authors.affiliation: Laboratory for Bone Metabolism and Regeneration, Faculty of Dental Medicine, Universidade do Porto, Porto, Portugal. Electronic address: mhfernandes@fmd.up.pt.
authors.forename: Maria Helena
authors.initials: MH
authors.lastname: Fernandes
mesh_terms: D000469:Alkaline Phosphatase / Q000378:metabolism; D017607:Aluminum Compounds / Q000494:pharmacology*; D000818:Animals; D017610:Calcium Compounds / Q000494:pharmacology*; D049109:Cell Proliferation / Q000187:drug effects; D002478:Cells, Cultured; D004305:Dose-Response Relationship, Drug; D004338:Drug Combinations; D042783:Endothelial Cells / Q000187:drug effects / Q000502:physiology; D006801:Humans; D051379:Mice; D018919:Neovascularization, Physiologic / Q000187:drug effects*; D010006:Osteoblasts / Q000187:drug effects / Q000502:physiology; D010012:Osteogenesis / Q000187:drug effects*; D010087:Oxides / Q000494:pharmacology*; D012387:Root Canal Filling Materials / Q000494:pharmacology*; D017640:Silicates / Q000494:pharmacology*; D013234:Stem Cells / Q000187:drug effects / Q000502:physiology
chemical_list: D017607:Aluminum Compounds; D017610:Calcium Compounds; D004338:Drug Combinations; D010087:Oxides; D012387:Root Canal Filling Materials; D017640:Silicates; C086631:mineral trioxide aggregate; D000469:Alkaline Phosphatase
keywords: Angiogenesis; calcium silicate endodontic sealers; human endothelial cells; human mesenchymal stem cells; osteogenesis