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

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

Research output: Contribution to journalArticleAcademicpeer-review

22 Citations (Scopus)


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

Original languageEnglish
Pages (from-to)271-280
Number of pages10
JournalMaterials Science and Engineering C
Publication statusPublished - 1 Mar 2018
Externally publishedYes


  • Bone morphogenetic protein-2
  • Microspheres
  • Protein delivery
  • Bone regeneration
  • Surface Plasmon Resonance
  • Cell Line
  • Microscopy, Electron, Scanning
  • Enzyme-Linked Immunosorbent Assay
  • Humans
  • Recombinant Proteins/biosynthesis
  • Bone Morphogenetic Protein 2/analysis
  • Collagen Type I/chemistry
  • Particle Size
  • Drug Carriers/chemistry
  • Animals
  • Drug Liberation
  • Mice


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