In this thesis, development of a bone regeneration therapy using biomaterials and growth factors is described. Initially, collagen I based recombinant protein (RCP) microspheres were developed for BMP-2 delivery. Among several parameters investigated, size and crosslinking of microspheres affected the BMP-2 release. To improve bone formation, we have combined microspheres with in-situ gelling hydrogels. Two types of alginate, high mannuronate (SLM) and high guluronate (SLG), and one type of thermosensitive hyaluronic acid were developed for this study. These hydrogels were designed not only to deliver and keep the microspheres at the site but also to act as a scaffold for the regenerating tissue and to fill a defect. The SLG alginate-RCP microspheres formulation was selected for further studies in ectopic and orthotopic bone formation models in rats. First, the effect of BMP-2 dose delivered was tested in the ectopic bone model using 10, 3, 1, 0.3 and 0 μg BMP-2 per implant. In a subsequent calvarial defect experiment, 50 μg/mL and 5 μg/mL BMP-2 containing hydrogels were tested. This study showed that the effective concentration of BMP-2 to induce both ectopic and orthotopic bone is optimally between 15-50 μg/mL.

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Keywords Bone morphogenetic protein-2, slow release, recombinant collagen, microspheres, bone regeneration
Promotor G.J.V.M. van Osch (Gerjo) , S.G.J.M. Kluijtmans (Sebastiaan)
Publisher Erasmus University Rotterdam
Sponsor The research leading to these results has received funding from the People Programme (Marie Curie Actions) of the European Union's Seventh Framework Programme FP7/2007- 2013/ under REA grant agreement n° 607051.
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Grant This work was funded by the European Commission 7th Framework Programme; grant id fp7/607051 - BIO INSPIRED BONE REGENERATION (BIO-INSPIRE)
Mumcuoglu Guvenc, Z.D. (2018, May 9). Development of an injectable slow release system for bone morphogenetic protein-2. Erasmus University Rotterdam. Retrieved from