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Collagen I derived recombinant protein microspheres as novel delivery vehicles for bone morphogenetic protein-2

By Didem Mumcuoglu, Laura de Miguel, Shehrazade Jekhmane, Claudia Siverino, Joachim Nickel, Thomas D Mueller, Johannes P van Leeuwen, Gerjo J V M van Osch and Sebastiaan G J M Kluijtmans


\u3cp\u3eBone morphogenetic protein-2 (BMP-2) is a powerful osteoinductive protein; however, there is a need for the development of a safe and efficient BMP-2 release system for bone regeneration therapies. Recombinant extracellular matrix proteins are promising next generation biomaterials since the proteins are well-defined, reproducible and can be tailored for specific applications. In this study, we have developed a novel and versatile BMP-2 delivery system using microspheres from a recombinant protein based on human collagen I (RCP). In general, a two-phase release pattern was observed while the majority of BMP-2 was retained in the microspheres for at least two weeks. Among different parameters studied, the crosslinking and the size of the RCP microspheres changed the in vitro BMP-2 release kinetics significantly. Increasing the chemical crosslinking (hexamethylene diisocyanide) degree decreased the amount of initial burst release (24 h) from 23% to 17%. Crosslinking by dehydrothermal treatment further decreased the burst release to 11%. Interestingly, the 50 and 72 μm-sized spheres showed a significant decrease in the burst release compared to 207-μm sized spheres. Very importantly, using a reporter cell line, the released BMP-2 was shown to be bioactive. SPR data showed that N-terminal sequence of BMP-2 was important for the binding and retention of BMP-2 and suggested the presence of a specific binding epitope on RCP (K \u3csub\u3eD\u3c/sub\u3e: 1.2 nM). This study demonstrated that the presented RCP microspheres are promising versatile BMP-2 delivery vehicles. \u3c/p\u3

Publisher: 'Elsevier BV'
Year: 2018
OAI identifier:
Provided by: Repository TU/e
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