Cell Therapy for the Enhancement of Bone Repair - Engineered Bone: Tissue Engineering Intelligence Unit - page 159

Figure 4. Radiograms of cell loaded bioceramic cylinders and control implanted in the animal tibia. A)
BMSC loaded porous HA; B) cell free control HA. Radiograms were taken 2 month after transplantation
in the sheep tibia model. Union was established rapidly at the bone/HA interface. Callus formation was
more extensive in BMSC loaded samples.
a long bone. The surgical defect was always of critical size (i.e., it would not heal by itself ). The
removed bone segment was substituted with a cylinder of porous bioceramic loaded with au-
tologous “in vitro” expanded osteogenic progenitors. A fixation device, either internal or exter-
nal, was used to stabilize the bone segment and discharge the mechanical load. Animals were
monitored by non invasive analysis at regular time intervals. In genera, lesion repair proceeded
quite rapidly. After sacrifice, specimens were retrieved and histological analysis performed.
Integration host bone/implant was excellent. The amount of bone observed was significantly
higher in the scaffolds loaded with osteoprogenitors than in controls where only the bioceramic
scaffold had been implanted. Both woven and lamellar bone had filled most of the pores of the
implants loaded with osteogenic cells. As tested in an indentation assay, the stiffness of the
composite bioceramic-bone was found to be higher in cell-loaded implants compared to
bioceramic only control implants 23 (Fig. 4).
It is worth mentioning that these studies differed significantly for what was concerning the
animal model (dog, sheep), the anatomical segment (femur, tibia), the nature (synthetic, natu-
ral) the chemical composition, the geometry and the resorbability of the biomaterial used. 22-24,88
Still the results were in good agreement suggesting an important advantage in bone formation
and therefore in the healing of the segmental defect when marrow stroma derived
osteoprogenitors were delivered together with the bioceramic scaffolds.
Clinical Studies
It is surprising that after the initial enthusiasm demonstrated by the flourishing of large
animal studies, whose results were all substantially in good agreement and very encouraging,
only one clinical pilot study has been performed. 25 Recently, Quarto and coworkers have trans-
posed the cell-based tissue engineering approach verified in large animals, in the clinical setting