Article,

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

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Mater Sci Eng C Mater Biol Appl, (2018)Mumcuoglu, Didem de Miguel, Laura Jekhmane, Shehrazade Siverino, Claudia Nickel, Joachim Mueller, Thomas D van Leeuwen, Johannes P van Osch, Gerjo J Kluijtmans, Sebastiaan G eng Netherlands 2018/03/10 Mater Sci Eng C Mater Biol Appl. 2018 Mar 1;84:271-280. doi: 10.1016/j.msec.2017.11.031. Epub 2017 Dec 1..
DOI: 10.1016/j.msec.2017.11.031

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 (24h) from 23% to 17%. Crosslinking by dehydrothermal treatment further decreased the burst release to 11%. Interestingly, the 50 and 72mum-sized spheres showed a significant decrease in the burst release compared to 207-mum 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(D): 1.2nM). This study demonstrated that the presented RCP microspheres are promising versatile BMP-2 delivery vehicles.

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