Title: Time kinetics of bone defect healing in response to BMP-2 and GDF-5 characterised by in vivo biomechanics

Author: D Wulsten, V Glatt, A Ellinghaus, K Schmidt-Bleek, A Petersen, H Schell, J Lienau, W Sebald, F Plöger, P Seemann, GN Duda

Address: Julius Wolff Institute and Center for Musculoskeletal Surgery, Berlin-Brandenburg Center for Regenerative Therapies, Charité - Universitätsmedizin Berlin, Augustenburger Platz 1, D-13353 Berlin, Germany

E-mail: georg.duda at charite.de

Key Words: Large segmental defects, bone healing, bone morphogenetic protein, growth and differentiation factor, small animal model.

Publication date: February 11th 2011

Abstract:

This study reports that treatment of osseous defects with different growth factors initiates distinct rates of repair. We developed a new method for monitoring the progression of repair, based upon measuring the in vivo mechanical properties of healing bone. Two different members of the bone morphogenetic protein (BMP) family were chosen to initiate defect healing: BMP-2 to induce osteogenesis, and growth-and-differentiation factor (GDF)-5 to induce chondrogenesis. To evaluate bone healing, BMPs were implanted into stabilised 5 mm bone defects in rat femurs and compared to controls. During the first two weeks, in vivo biomechanical measurements showed similar values regardless of the treatment used. However, 2 weeks after surgery, the rhBMP-2 group had a substantial increase in stiffness, which was supported by the imaging modalities. Although the rhGDF-5 group showed comparable mechanical properties at 6 weeks as the rhBMP-2 group, the temporal development of regenerating tissues appeared different with rhGDF-5, resulting in a smaller callus and delayed tissue mineralisation. Moreover, histology showed the presence of cartilage in the rhGDF-5 group whereas the rhBMP-2 group had no cartilaginous tissue.
Therefore, this study shows that rhBMP-2 and rhGDF-5 treated defects, under the same conditions, use distinct rates of bone healing as shown by the tissue mechanical properties. Furthermore, results showed that in vivo biomechanical method is capable of detecting differences in healing rate by means of change in callus stiffness due to tissue mineralisation.

Article download: Pages 177-192 (PDF file)
DOI: 10.22203/eCM.v021a14