Stimulation of bone healing by sustained bone morphogenetic protein 2 (BMP-2) delivery

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Abstract

The aim of the study was to investigate the effect of a sustained release of bone morphogenetic protein2 (BMP-2) incorporated in a polymeric implant coating on bone healing. In vitro analysis revealed a sustained, but incomplete BMP-2 release until Day 42. For the in vivo study, the rat tibia osteotomy was stabilized either with control or BMP-2 coated wires, and the healing progress was followed by micro computed tomography (μCT), biomechanical testing and histology at Days 10, 28, 42 and 84. MicroCT showed an accelerated formation of mineralized callus, as well as remodeling and an increase of mineralized/total callus volume (p = 0.021) at Day 42 in the BMP-2 group compared to the control. Histology revealed an increased callus mineralization at Days 42 and 84 (p = 0.006) with reduced cartilage at Day 84 (p = 0.004) in the BMP-2 group. Biomechanical stiffness was significantly higher in the BMP-2 group (p = 0.045) at Day 42. In summary, bone healing was enhanced after sustained BMP-2 application compared to the control. Using the same drug delivery system, but a burst release of BMP-2, a previous published study showed a similar positive effect on bone healing. Distinct differences in the healing outcome might be explained due to the different BMP release kinetics and dosages. However, further studies are necessary to adapt the optimal release profiles to physiological mechanisms. © 2014 by the authors; licensee MDPI, Basel, Switzerland.

Figures

  • Figure 1. Cumulative bone morphogenetic protein 2 (BMP-2) release from the poly(D,L-lactide) (PDLLA) implant coating (n = 3). Mean values with standard deviation are depicted.
  • Figure 2. (a) µCT 3D reconstructions of selected tibiae of the control and the BMP-2 group over the healing time points. The scans were performed with the Viva40 µCT (Scanco) with a voxel size of 25 µm. The cortical bone has been removed. Scale bar: 1 mm; (b) Results of the µCT analysis of the control (ctrl) and the BMP-2 treated groups. The first graph shows the bone volume and total volume (total callus volume, including bone volume), and the percentage amount of mineralized bone in the total callus region is depicted in the second graph. The bone volume/total volume (in %) was significantly increased at Day 42 in the BMP-2 group compared to the control group.
  • Figure 3. Histological staining of the calluses of the control and the BMP-2 group at Days 28 and 84. Movat pentachrome stainings of the two groups (control group: a,b; and BMP-2 group: c,d) at Days 28 (a,c) and 84 (b,d). The arrows point to the osteotomy gap. At Day 28, the calluses of both groups showed no fully mineralized bridging, as fibrous tissue was still filling the gap above the osteotomy. After 84 days, the healing progressed with fully mineralized callus in the BMP-2 group. Scale bar: 500 µm.
  • Figure 4. Histomorphometry-based data of the callus composition (mineralized tissue area and cartilage tissue area relative to the total callus area) over time. The mineralization of the callus was significantly enhanced in the BMP-2 group at Days 42 and 84 (p = 0.006), whereas the cartilage area was significantly reduced after BMP-2 treatment at Day 84 (p = 0.004).
  • Figure 5. Results of the biomechanical testing of osteotomized tibiae expressed as normalized stiffness to the respective intact tibia.
  • Table 1. Number of animals and investigated parameters of the osteotomized tibia at the different post-operative time points.

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APA

Faßbender, M., Minkwitz, S., Strobel, C., Schmidmaier, G., & Wildemann, B. (2014). Stimulation of bone healing by sustained bone morphogenetic protein 2 (BMP-2) delivery. International Journal of Molecular Sciences, 15(5), 8539–8552. https://doi.org/10.3390/ijms15058539

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