Among the different biomaterials considered as scaffolds for bone tissue engineering, calcium phosphate based ceramics have proven to be of great interest given their osteoconductivity and their ability to “integrate” with the bone tissue. We were the first to report the repair of large bone defects in humans by the use of autologous in vitro expanded bone marrow stromal cells (BMSC) associated to a 100% HA porous ceramic. A good integration of the implants with the pre-existing bone was maintained during the more than 7 year follow-up period and no major adverse conditions were observed. Nevertheless an important bias of this pilot study was represented by the low resorbability of the porous HA bioceramics. Therefore resorbable porous ceramic constructs, based on silicon-stabilized tricalcium phosphate, were implanted in critical-size defects of sheep tibias, either alone or after seeding with bone marrow stromal cells (BMSC). Only BMSC-loaded ceramics displayed a progressive scaffold resorption, coincident with new bone deposition. To investigate the coupled mechanisms of bone formation and scaffold resorption, X-ray computed microtomography with synchrotron radiation (mCT) was performed on BMSC-seeded ceramic cubes before and after implantation in immunodeficient mice for 2 or 6 months. With increasing implantation time, scaffold thickness significantly decreased while bone thickness increased.  All scaffolds had a uniform density distribution before implantation. Areas of different densities were instead observed, in the same scaffolds, once seeded with cells and implanted in vivo. A mX-ray diffraction analysis revealed that at the bone/scaffold interface, the TCP component of the biomaterial decreased much faster than the HA component, highlighting coupling and cell-dependency of the resorption and matrix deposition mechanisms. Moreover, in scaffolds implanted without cells the TCP:HA ratio remained unchanged with respect to the pre-implantation analysis.

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