Critical assessment of rhBMP-2 mediated bone induction: an in vitro and in vivo evaluation

Marta Kisiel, Manuela Ventura, Oommen Podiyan Oommen, Anu George, X Frank Walboomers, Jöns Hilborn, Oommen P Varghese

    Research output: Contribution to journalArticleScientificpeer-review

    38 Citations (Scopus)


    Understanding the influence of formulation and storage conditions on rhBMP-2 bioactivity is extremely important for its clinical application. Reports in the literature show that different research groups employ different parameters such as formulation conditions, storage, doses for in vivo applications etc. that makes it difficult to correlate results from different experiments. We therefore decided to rationalize these anomalies by performing a basic study on such parameters using two commercially available BMPs. Our in vitro experiments suggest that BMPs from different sources have significant differences in their bioactivity. The clinically approved rhBMP-2 (InductOs®; BMP-P) showed superior stability, compared to rhBMP-2 from R&D Systems (BMP-R) at physiological pH (determined by ALP assay). This BMP-P also showed lower binding to polypropylene Eppendorf tube. The BMP-R almost lost its bioactivity within 30 min at physiological pH and also shows more adhesion to plastic surfaces. This aggregation behavior was unequivocally ascertained by performing light scattering studies of the two BMPs, which revealed linear aggregation with time for BMP-R unlike BMP-P. The in vitro results were also reflected in the in vivo experiments, in a rat ectopic model with injectable hyaluronic acid (HA) hydrogel as BMP carrier. After 7 weeks post-implantation we observed larger bone volume with oriented collagen in the BMP-P group but a smaller bone with disoriented collagen in the BMP-R case. Our results highlight the large difference in activity between seemingly identical substances and also the importance of proper handling of such sensitive proteins.

    Original languageEnglish
    Pages (from-to)646-53
    Number of pages8
    JournalJournal of Controlled Release
    Issue number3
    Publication statusPublished - 28 Sept 2012
    Publication typeA1 Journal article-refereed


    • Aldehydes
    • Alkaline Phosphatase
    • Animals
    • Bone Morphogenetic Protein 2
    • Cell Line
    • Cell Proliferation
    • Cell Survival
    • Collagen
    • Drug Carriers
    • Drug Stability
    • Hyaluronic Acid
    • Hydrazines
    • Hydrogels
    • Hydrogen-Ion Concentration
    • Male
    • Mice
    • NIH 3T3 Cells
    • Osteogenesis
    • Rats
    • Rats, Sprague-Dawley
    • Recombinant Proteins
    • Rheology
    • Transforming Growth Factor beta
    • Comparative Study
    • Journal Article
    • Research Support, Non-U.S. Gov't


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