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

 
: Mumcuoglu, D.; Miguel, L. de; Jekhmane, S.; Siverino, C.; Nickel, J.; Mueller, T.D.; Leeuwen, J.P. van; Osch, G.J. van; Kluijtmans, S.G.

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Materials Science and Engineering, C. Biomimetic and supramolecular systems Biomimetic materials, sensors and systems 84 (2018), pp.271-280
ISSN: 0928-4931
ISSN: 1873-0191
English
Journal Article
Fraunhofer IGB ()

Abstract
Bone 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 (KD: 1.2 nM). This study demonstrated that the presented RCP microspheres are promising versatile BMP-2 delivery vehicles.

: http://publica.fraunhofer.de/documents/N-524861.html