title: In vitro release of dimethyloxaloylglycine and l-mimosine from bovine bone mineral.
abstract: OBJECTIVE
  Prolyl hydroxylases (PHD) are oxygen sensors and therefore pharmacological targets to stimulate periodontal regeneration. Here we evaluate the release profile of the PHD inhibitors dimethyloxaloylglycine and l-mimosine from bone substitutes.
  
  
  METHODS
  Dimethyloxaloylglycine and l-mimosine were lyophilised onto bone substitutes including bovine bone mineral, beta-tricalcium phosphate, and hydroxyapatite. Release kinetic was evaluated by bioassays with gingival and periodontal ligament fibroblasts. We determined the capacity of PHD inhibitors to provoke VEGF expression and to repress metabolic activity and proliferation as assessed by immunoassay, MTT conversion and (3)[H]thymidine incorporation, respectively.
  
  
  RESULTS
  We found that the PHD inhibitors are released from bovine bone mineral as indicated by the increase of VEGF production in gingival and periodontal ligament fibroblasts. Supernatants obtained after 1h also decreased metabolic activity and proliferation of the fibroblasts. A fibrin matrix prolonged the release of PHD inhibitors up to 192h. A similar cellular response was found when supernatants from PHD inhibitors loaded beta-tricalcium phosphate and hydroxyapatite embedded in fibrin were assessed.
  
  
  CONCLUSIONS
  In conclusion bone substitutes can serve as carriers for PHD inhibitors that maintain their capacity to provoke a pro-angiogenic response in vitro. These findings provide the basis for preclinical studies to evaluate if this release kinetic can stimulate periodontal regeneration.
authors: Department of Conservative Dentistry and Periodontology, Medical University of Vienna, Austria; Austrian Cluster for Tissue Regeneration, Austria. Electronic address: hermann.agis@meduniwien.ac.at.
authors: Hermann
authors: H
authors: Agis
authors: Austrian Cluster for Tissue Regeneration, Austria; Department of Oral Surgery, Medical University of Vienna, Austria.
authors: Lisa
authors: L
authors: Hueber
authors: Austrian Cluster for Tissue Regeneration, Austria; Department of Oral Surgery, Medical University of Vienna, Austria.
authors: Niloufar
authors: N
authors: Pour Sadeghian
authors: Austrian Cluster for Tissue Regeneration, Austria; Department of Oral Surgery, Medical University of Vienna, Austria.
authors: Manuela
authors: M
authors: Pensch
authors: Austrian Cluster for Tissue Regeneration, Austria; Department of Oral Surgery, Medical University of Vienna, Austria; Laboratory of Oral Cell Biology, School of Dental Medicine, University of Bern, Switzerland.
authors: Reinhard
authors: R
authors: Gruber
mesh_terms: D000600:Amino Acids, Dicarboxylic / Q000378:metabolism*; D000818:Animals; D018786:Bone Substitutes / Q000494:pharmacology*; D002417:Cattle; D005347:Fibroblasts / Q000378:metabolism*; D005881:Gingiva / Q000166:cytology; D066298:In Vitro Techniques; D008855:Microscopy, Electron, Scanning; D008898:Mimosine / Q000378:metabolism*; D008903:Minerals / Q000494:pharmacology*; D010513:Periodontal Ligament / Q000166:cytology; D042461:Vascular Endothelial Growth Factor A / Q000378:metabolism
chemical_list: D000600:Amino Acids, Dicarboxylic; C077540:Bio-Oss; D018786:Bone Substitutes; D008903:Minerals; D042461:Vascular Endothelial Growth Factor A; D008898:Mimosine; C040947:oxalylglycine
keywords: Bone substitute material; Fibroblast; Periodontal regeneration; Prolyl-hydroxylase inhibitors; Vascular endothelial growth factor