title: Release kinetics of prolyl hydroxylase inhibitors from collagen barrier membranes.
abstract: Collagen barrier membranes are used in guided tissue regeneration to support healing. This strategy, however, relies on the healing capacity of the tissue. Pharmacological inhibitors of prolyl hydroxylases can support regeneration by enhancing angiogenesis and are therefore a promising tool for periodontology. Here we evaluate the release kinetics of the prolyl hydroxylase inhibitors dimethyloxalylglycine and L-mimosine from collagen barrier membranes. Dimethyloxalylglycine and L-mimosine were lyophilized onto the collagen barrier membranes. The morphology of the collagen barrier membranes was analysed using scanning electron microscopy. The release of prolyl hydroxylase inhibitors was assessed by colorimetric and spectroscopic methods. Their ability to induce a cellular response was assessed in bioassays with gingival and periodontal ligament fibroblasts based on vascular endothelial growth factor production, proliferation, and metabolic activity of the cells. We found that loading of collagen barrier membranes with prolyl hydroxylase inhibitors did not change the overall membrane morphology. Assessment of the release kinetics by direct measurements and based on vascular endothelial growth factor production showed that supernatants obtained from the collagen barrier membranes in the first 6 hours had a sufficient level of prolyl hydroxylase inhibitors to induce vascular endothelial growth factor production. A similar kinetic was found when cell proliferation was assessed. Changes in metabolic activity did not reach the level of significance in the MTT assay. In conclusion, collagen barrier membranes can release prolyl hydroxylase inhibitors thereby increasing the pro-angiogenic capacity of periodontal cells in vitro. These findings provide the basis for preclinical studies to evaluate the regenerative capacity of prolyl hydroxylase inhibitors in periodontology and oral surgery.
authors.affiliation: Department of Oral Surgery, Medical University of Vienna, Vienna, Austria Department of Conservative Dentistry and Periodontology, Medical University of Vienna, Vienna, Austria.
authors.forename: Omar
authors.initials: O
authors.lastname: Hamid
authors.affiliation: Department of Oral Surgery, Medical University of Vienna, Vienna, Austria Department of Conservative Dentistry and Periodontology, Medical University of Vienna, Vienna, Austria.
authors.forename: Manuela
authors.initials: M
authors.lastname: Pensch
authors.affiliation: Department of Conservative Dentistry and Periodontology, Medical University of Vienna, Vienna, Austria Austrian Cluster for Tissue Regeneration, Vienna, Austria hermann.agis@meduniwien.ac.at.
authors.forename: Hermann
authors.initials: H
authors.lastname: Agis
mesh_terms: D000600:Amino Acids, Dicarboxylic / Q000008:administration & dosage / Q000493:pharmacokinetics; D001672:Biocompatible Materials; D002478:Cells, Cultured; D003094:Collagen / Q000378:metabolism* / Q000648:ultrastructure; D005881:Gingiva / Q000166:cytology / Q000187:drug effects / Q000378:metabolism; D016557:Guided Tissue Regeneration, Periodontal / Q000379:methods*; D006801:Humans; D008422:Materials Testing; D008567:Membranes, Artificial; D008855:Microscopy, Electron, Scanning; D008898:Mimosine / Q000008:administration & dosage / Q000493:pharmacokinetics; D018919:Neovascularization, Physiologic / Q000187:drug effects; D064800:Prolyl-Hydroxylase Inhibitors / Q000008:administration & dosage* / Q000493:pharmacokinetics*; D042461:Vascular Endothelial Growth Factor A / Q000096:biosynthesis
chemical_list: D000600:Amino Acids, Dicarboxylic; D001672:Biocompatible Materials; D008567:Membranes, Artificial; D064800:Prolyl-Hydroxylase Inhibitors; C467484:VEGFA protein, human; D042461:Vascular Endothelial Growth Factor A; D008898:Mimosine; D003094:Collagen; C040947:oxalylglycine
keywords: Guided tissue regeneration; biomaterials; bone regeneration; growth factors; material sciences