In vitro release of dimethyloxaloylglycine and l-mimosine from bovine bone mineral.

Agis, Hermann; Hueber, Lisa; Pour Sadeghian, Niloufar; Pensch, Manuela; Gruber, Reinhard (2014). In vitro release of dimethyloxaloylglycine and l-mimosine from bovine bone mineral. Archives of oral biology, 59(10), pp. 1024-1031. Elsevier Science 10.1016/j.archoralbio.2014.05.027

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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. MATERIALS 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.

Item Type:

Journal Article (Original Article)


04 Faculty of Medicine > School of Dental Medicine > School of Dental Medicine, Oral Surgery Research

UniBE Contributor:

Gruber, Reinhard


600 Technology > 610 Medicine & health




Elsevier Science




Eveline Carmen Schuler

Date Deposited:

22 Jan 2015 11:26

Last Modified:

25 Jan 2017 12:15

Publisher DOI:


PubMed ID:


Uncontrolled Keywords:

Bone substitute material, Fibroblast, Periodontal regeneration, Prolyl-hydroxylase inhibitors, Vascular endothelial growth factor




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