Search

Stem cell-mediated gene therapy for fracture repair, utilizes genetically engineered mesenchymal stem cells (MSCs) for the induction of bone growth and is considered a promising approach in skeletal tissue regeneration. Previous studies have shown that murine nonunion fractures can be repaired by implanting MSCs over-expressing recombinant human bone morphogenetic protein-2 (rhBMP-2). Nanoindentation studies of bone tissue induced by MSCs in a radius fracture site indicated similar elastic modulus compared to intact murine bone, eight weeks post treatment. In the present study we sought to investigate temporal changes in microarchitecture and biomechanical properties of repaired murine radius bones, following the implantation of MSCs. High resolution micro computed tomography (Micro-CT) was performed 10 and 35 weeks post MSC implantation, followed by micro finite element (Micro-FE) analysis. The results have shown that the regenerated bone tissue remodels over time, as indicated by a significant decrease in bone volume, total volume and connectivity density combined with an increase in mineral density. In addition, the axial stiffness of limbs repaired with MSCs was 2 to 1.5 times higher compared to the contralateral intact limbs, at 10 and 35 weeks post treatment. These results could be attributed to the fusion that occurred between in the ulna and radius bones. In conclusion, although MSCs induce bone formation, which exceeds the fracture site, significant remodeling of the repair callus occurs over time. In addition, limbs treated with an MSC graft demonstrated superior biomechanical properties, which could indicate the clinical benefit of future MSC application in nonunion fracture repair.

The human parathyroid peptide fragment hPTH 134 is an anabolic drug which, given intermittently, turns on bone remodeling by increasing bone formation. Its exact mode of action is however still unclear to date. In an earlier study, we found that in mechanically loaded animals, formation occurs preferentially at highly loaded areas, and resorption at lowly strained areas [1]. Here we investigate if and how PTH combined with mechanical loading alters the mechanoregulation of bone remodeling. With this, we aimed at a better understanding of the effectiveness of PTH in the treatment of bone diseases such as osteoporosis.

It is widely accepted that osteocytes transduce mechanical signals in bone. To better understand the micromechanical response of the osteocyte lacunae to imposed macroscopic strains finite element (FE) models were introduced to predict how mechanical loads act on the lacuno canalicular network (LCN). Yet these FE analyses were based on idealized LCN models. Recent progress in imaging allows quantitative assessment of bone microstructure in 3D down to the level of individual osteocyte lacunae and its canaliculi. Our goal was to study the influence of the microstructure on the mechanical response to imposed macroscopic strains by combining true 3D LCN data with image based FE modeling.