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

92 Citations (Scopus)

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

Fingerprint

Bone Morphogenetic Protein 2
Fibrin
Solubility
Dogs
Bone and Bones
Autografts
Skull
Standard of Care
Wrist
Glycosylation
Canidae
Joints
Clinical Trials
Proteins

Keywords

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

ASJC Scopus subject areas

  • Orthopedics and Sports Medicine

Cite this

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

Bone healing in the rat and dog with nonglycosylated BMP-2 demonstrating low solubility in fibrin matrices. / Schmoekel, Hugo; Schense, Jason C.; Weber, Franz E.; Grätz, Klaus W.; Gnägi, Dania; Müller, Ralph; Hubbell, Jeffrey A.

In: Journal of Orthopaedic Research, Vol. 22, No. 2, 12.02.2004, p. 376-381.

Research output: Contribution to journalArticle

Schmoekel, H, Schense, JC, Weber, FE, Grätz, KW, Gnägi, D, Müller, R & Hubbell, JA 2004, 'Bone healing in the rat and dog with nonglycosylated BMP-2 demonstrating low solubility in fibrin matrices', Journal of Orthopaedic Research, vol. 22, no. 2, pp. 376-381. https://doi.org/10.1016/S0736-0266(03)00188-8
Schmoekel, Hugo ; Schense, Jason C. ; Weber, Franz E. ; Grätz, Klaus W. ; Gnägi, Dania ; Müller, Ralph ; Hubbell, Jeffrey A. / Bone healing in the rat and dog with nonglycosylated BMP-2 demonstrating low solubility in fibrin matrices. In: Journal of Orthopaedic Research. 2004 ; Vol. 22, No. 2. pp. 376-381.
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