In Vitro and In Vivo Correlation of BMP-2 Release Profiles from Complex Delivery Vehicles

Maurits Geert Laurent Olthof, Marianna A Tryfonidou, Mahrokh Dadsetan, Wouter Dhert, Michael J Yaszemski, Diederik H R Kempen, Lichun Lu*

*Corresponding author for this work

Research output: Contribution to journalArticleAcademicpeer-review

Abstract

Local sustained delivery of bioactive molecules from biomaterials is a promising strategy to enhance bone regeneration. To optimize delivery vehicles for bone formation, the design characteristics are tailored with consequential effect on BMP-2 release and bone regeneration. Complying with the 3R principles, the growth factor release is often investigated in vitro using several buffers to mimic the in vivo physiological environment. However, this remains an unmet need. Therefore, this study investigates the correlation between the in vitro and in vivo (IVIVC) BMP-2 release from complex delivery vehicles in several commonly used in vitro buffers: cell culture model, phosphate buffered saline, and a strong desorption buffer. The results from this study showed that the release environment affected the BMP-2 release profiles, creating distinct relationships between release versus time and differences in extent of release. According to the guidance set by the U.S. Food and Drug Administration (FDA), in vitro- in vivo correlation resulted in level A internal predictability for individual composites. Since the IVIVC was influenced by the BMP-2 loading method and composite surface chemistry, the external predictive value of the IVIVCs was limited. These results show that the IVIVCs can be used for predicting the release of an individual composite. However, the models cannot be used for predicting in vivo release for different composite formulations since they lack external predictability. Potential confounding effects of drug type, delivery vehicle formulations and application site should be added to the equation to develop one single IVIVC applicable for complex delivery vehicles. Altogether, these results imply that more sophisticated in vitro systems should be used in bone regeneration to accurately discriminate and predict in vivo BMP-2 release from different complex delivery vehicles.

Original languageEnglish
Pages (from-to)379-390
JournalTissue engineering. Part C, Methods
Volume24
Issue number7
DOIs
Publication statusPublished - 1 Jul 2018

Keywords

  • bone morphogenetic protein-2 release
  • bone regeneration
  • In vitro-in vivo correlation
  • ogilo(polyethelene glycol) fumarate

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