Bone healing in the rat and dog with nonglycosylated BMP-2 demonstrating low solubility in fibrin matrices

Hugo Schmoekel, Jason C. Schense, Franz E. Weber, Klaus W. Grätz, Dania Gnägi, Ralph Müller, Jeffrey A. Hubbell

Research output: Contribution to journalArticle

96 Scopus citations

Abstract

A novel form of recombinant human bone morphogenetic protein-2 (BMP-2) was explored for effective incorporation and long-term retention into fibrin ingrowth matrices. The solubility of native BMP-2 is greatly dependent on its glycosylation. To enhance retention of BMP-2 in fibrin matrices, a nonglycosylated form (nglBMP-2), which is less soluble than the native glycosylated protein, was produced recombinantly and evaluated in critical-size defects in the rat calvarium (group n=6). When 1 or 20 μg nglBMP-2 was incorporated by precipitation within the matrix, 74 ± 4% and 98 ± 2% healing was observed in the rat calvarium, respectively, as judged radiographically by closure of the defect at 3 weeks. More soluble forms of BMP-2, used as controls, induced less healing, demonstrating a positive correlation between low solubility, retention in vitro, and healing in vivo. Subsequently, the utility of nglBMP-2 was explored in a prospective veterinary clinical trial for inter-carpal fusion in dogs, replacing the standard-of-care, namely autologous cancellous autograft, with nglBMP-2 in fibrin. In a study of 10 sequential canine patients, fibrin with 600 μg/ml nglBMP-2 performed better than autograft in the first weeks of bone healing and comparably thereafter. Furthermore, a greater fraction of animals treated with nglBMP-2 in fibrin demonstrated bone bridging across each of the treated joints at both 12 and 17 weeks than in animals treated with autograft. These results suggest that evaluation in a human clinical setting of nonglycosylated BMP-2 in fibrin matrices might be fruitful.

Original languageEnglish (US)
Pages (from-to)376-381
Number of pages6
JournalJournal of Orthopaedic Research
Volume22
Issue number2
DOIs
StatePublished - Feb 12 2004

Keywords

  • BMP-2
  • Bone defect
  • Controlled release
  • Fibrin
  • Glycosylation
  • Precipitation

ASJC Scopus subject areas

  • Orthopedics and Sports Medicine

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    Schmoekel, H., Schense, J. C., Weber, F. E., Grätz, K. W., Gnägi, D., Müller, R., & Hubbell, J. A. (2004). Bone healing in the rat and dog with nonglycosylated BMP-2 demonstrating low solubility in fibrin matrices. Journal of Orthopaedic Research, 22(2), 376-381. https://doi.org/10.1016/S0736-0266(03)00188-8