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

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.

BMP delivery complements the guiding effect of scaffold architecture without altering bone microstructure in critical-sized long bone defects: A multiscale analysis

“…However, often the scaffold alone is not able to induce formation of large volumes of new bone and additional BMP-mediated osteogenic stimulus is needed [4,5,16,17]. On the one hand, numerous preclinical [1][2][3][4][5][6][7][8][9][10][11][12][13][14][15][16][17] and clinical studies [18][19][20][21][22][23][24][25][26] have demonstrated that the use of BMPs results in (i) faster bone formation and (ii) larger bone volumes. On the other hand, it is well known that bone mechanical properties and function are determined by its hierarchical structure at different length scales [27,[29][30][31].…”

“…Numerous bone substitutes combining bone morphogenetic proteins (BMPs) are currently tested in order to reduce the need for bone graft transplantations. Recombinant human BMP-2 (rhBMP-2) [1][2][3][4][5][6][7][8][9][10] and rhBMP-7 [11][12][13][14][15][16][17] have proven successful in forming large volumes of new bone without autograft transplantation in critical-sized long bone defects in preclinical studies. Furthermore, these proteins are already in clinical use [18][19][20][21][22][23][24][25][26].…”

Mechanical Load Modulates the Stimulatory Effect of BMP2 in a Rat Nonunion Model

“…Both fixator designs were mounted to harvested cadaveric femurs of female 12-weekold Sprague Dawley rats (n = 6/fixator design) to undergo axial compression and torsional testing using published protocols. 36 The fixator design of the mechanically stimulated group resulted in an axial stiffness of 62.02 -13.52 N/ mm (mean -standard deviation) and a torsional stiffness of 15.35 -2.69 N/mm, and the fixator design of the unstimulated group produced an axial stiffness of 59.05 -14.45 N/mm and a torsional stiffness of 14.57 -2.03 N/mm.…”

“…1C2). 36 The fixator design allowed disassembly such that the fracture pins remained within the frame, but the defect bridging bar could be detached to allow mechanical loading. In all fixators four titanium threaded (0.65-mm core diameter/1.2-mm outer diameter) pinsfixed to the crossbar by thread tightening through compression of the fixator ensured fragment fixation.…”

“…For the mechanical loading, the external fixator was constrained to a custom-made setup, containing a precision linear actuator (M-230; Physik Instrumente) controlled by a Labview script (LabVIEW 8.5; National Instruments). 36 While the proximal 248 SCHWARZ ET AL.…”