Abstract
Summary
MSCs could promote bone regeneration in sheep when loaded on natural fully-resorbable scaffolds, but results are highly variable. Improving the ultimate performance of cell-containing constructs cannot be limited to the decreased rate of scaffold resorption.
Introduction. Tissue constructs containing mesenchymal stem cells (MSCs) are an appealing strategy for repairing massive segmental bone defects. However, their therapeutic effectiveness does not match that of autologous bone grafts; among the failure reasons the scaffold resorbability has been identified as a critical feature for achieving bone regeneration. In the present study, the osteogenic potential of 2 constructs obtained by expanding in a bioreactor autologous MSCs onto granules of Acropora or Porites coral, natural fully-resorbable scaffolds, was compared.
Materials and methods
15 sheep underwent a 25 mm long metatarsal ostectomy stabilised with a 3.5 DCP plate. Bone defects were replaced with (i) MSCs-Acropora constructs (n=7), (ii) MSCs-Porites constructs (n=6), (iii) autograft (n=2). Animals were sacrificed 4 months later and bone healing and coral resorption was documented by radiographic, histologic and microCT studies.
Results
Results were highly variable in both scaffold groups.
Bone formation. Non-union occurred in half cases of each group. In the other half, abundant new bone formation within the defect was observed. This permitted full bone regeneration in 2 animals from the Acropora group and 1 from the Porites group. MicroCT and histomorphometric analysis confirmed great variations as regard of the amount of newly formed bone in defects. Two Acropora-filled defects showed greater amount of newly formed bone than all the Porites-filled defects and were equivalent to the autograft-filled defects, however the difference between the 2 groups wasn't significant.
In all groups, the amount of newly formed bone was similar in the proximal, central, and distal thirds of the defects.
Coral resorption. The quantitative analysis provided evidence that the Acropora scaffold resorption rate was slower than the Porites one. Bone formation was not statistically associated with coral resorption. However, the 2 Acropora-filled defects with the highest rate of resorption showed a less extend bone formation.
Discussion and conclusions
Interestingly, osteogenesis within the 2 constructs was not only found continuous with the bony stumps, but also at the core of the implants. Moreover, bone was observed inside the residual coral fragments. Scaffold resorption was almost complete at 4 months, leading to full bone regeneration in 3 animals. These results provided evidence that MSCs could promote bone regeneration in sheep when loaded on a natural fully-resorbable scaffold. The capacity of the 2 scaffolds to repair defects is statistically similar, despite their different resorption rates and kinetics. This finding suggests that improving the ultimate performance of cell-containing constructs cannot be limited to the decreased rate of scaffold resorption.
