Micro-finite element model; Micro-computed tomography; Bone tissue regeneration; Mesenchymal stem cells
Abstract :
[en] 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 2-1.5 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 in between 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. (C) 2010 Elsevier Ltd. All rights reserved.
Disciplines :
Laboratory medicine & medical technology Biochemistry, biophysics & molecular biology
Author, co-author :
Kallai, Ilan ✱; Hebrew Univ Jerusalem, Hadassah Fac Dent Med, Skeletal Biotech Lab, IL-91120 Jerusalem, Israel.
van Lenthe, G. Harry ✱; ETH, Inst Biomech, Zurich, Switzerland.
Ruffoni, Davide ; Université de Liège - ULiège > Département d'aérospatiale et mécanique > Mécanique des matériaux biologiques et bioinspirés
✱ These authors have contributed equally to this work.
Language :
English
Title :
Quantitative, structural, and image-based mechanical analysis of nonunion fracture repaired by genetically engineered mesenchymal stem cells
Publication date :
2010
Journal title :
Journal of Biomechanics
ISSN :
0021-9290
eISSN :
1873-2380
Publisher :
Elsevier Sci Ltd, Oxford, United Kingdom
Volume :
43
Issue :
12
Pages :
2315-2320
Peer reviewed :
Peer Reviewed verified by ORBi
Funders :
National Institutes of Health [R01AR056694-01A1, R01DE019902-01]
Commentary :
We acknowledge funding from the National Institutes of Health Grants No. R01AR056694-01A1 and R01DE019902-01 (D.C. and G.P.). We thank the Swiss National Supercomputing Centre (CSCS) for granting computational time.
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