Mineral loss and increased bone fragility are common to different systemic and multi-factorial pathophysiological conditions, which involve hormonal, nutritional and mechanical determinants. Gravitational unloading during spaceflight leads to severe (1-2% bone mass loss/month), site-specific (cancellous weight-bearing bones) and time-/age-related skeletal alterations. In the present study we investigated the long-term effect of gravitational unloading (microgravity) on the structural and mechanical features of whole cancellous bone explants (rat tibial proximal epiphyses) kept in vitro for up to 4 weeks in the Rotating Cell Culture System (RCCS) bioreactor. Simulated microgravity (vector-averaged gravity) was obtained by setting RCCS operational conditions according to the specific experimental needs. Quantification of micro-structural changes in trabecular bone structure was performed by the Cell method (Patent: PTC-WO03/082118, Trieste University) applied to the static analysis of microstructures obtained from the 3D reconstruction of computed micro-tomography scans performed at the Elettra Synchrotron facility. The results obtained, consistent with the skeletal alterations observed in vivo after spaceflight, confirmed the value of our culture model. By allowing reproducible and controlled changes in specific biochemical and biomechanical factors, our RCCS bioreactor-based culture system demonstrated to provide the technological means to investigate, in vitro, fundamental mechanisms of bone cells function in a complex 3D microenvironment. Furthermore, the possibility to combine conventional histomorphologic, biochemical and molecular analyses with a numerical simulation able to quantify bone structural changes, open new perspectives for a better understanding of the mechanisms leading to bone loss in humans, and may help in the identification of more efficacious preventive/interventional strategies.
BIOREACTOR-BASED 3D CULTURE OF BONE EXPLANTS AND MICRO-STRUCTURAL NUMERICAL ANALYSIS OF BONE VOLUMES: NEW TOOLS FOR THE STUDY OF BONE LOSS PATHOPHYSIOLOGY AND TARGETED THERAPIES
COSMI, Francesca;
2009-01-01
Abstract
Mineral loss and increased bone fragility are common to different systemic and multi-factorial pathophysiological conditions, which involve hormonal, nutritional and mechanical determinants. Gravitational unloading during spaceflight leads to severe (1-2% bone mass loss/month), site-specific (cancellous weight-bearing bones) and time-/age-related skeletal alterations. In the present study we investigated the long-term effect of gravitational unloading (microgravity) on the structural and mechanical features of whole cancellous bone explants (rat tibial proximal epiphyses) kept in vitro for up to 4 weeks in the Rotating Cell Culture System (RCCS) bioreactor. Simulated microgravity (vector-averaged gravity) was obtained by setting RCCS operational conditions according to the specific experimental needs. Quantification of micro-structural changes in trabecular bone structure was performed by the Cell method (Patent: PTC-WO03/082118, Trieste University) applied to the static analysis of microstructures obtained from the 3D reconstruction of computed micro-tomography scans performed at the Elettra Synchrotron facility. The results obtained, consistent with the skeletal alterations observed in vivo after spaceflight, confirmed the value of our culture model. By allowing reproducible and controlled changes in specific biochemical and biomechanical factors, our RCCS bioreactor-based culture system demonstrated to provide the technological means to investigate, in vitro, fundamental mechanisms of bone cells function in a complex 3D microenvironment. Furthermore, the possibility to combine conventional histomorphologic, biochemical and molecular analyses with a numerical simulation able to quantify bone structural changes, open new perspectives for a better understanding of the mechanisms leading to bone loss in humans, and may help in the identification of more efficacious preventive/interventional strategies.Pubblicazioni consigliate
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