MSC-seeded dense collagen scaffolds with a bolus dose of VEGF promote healing of large bone defects
- Resource Type
- Authors
- M Chua; Janet E. Henderson; H Wang; F Jiang; Chan Gao; A Li; Y Liu; Brian P. Chen; Edward J. Harvey
- Source
- European Cells & Materials, Vol 26, Pp 195-207 (2013)
Scopus-Elsevier
- Subject
- Calcium Phosphates
Vascular Endothelial Growth Factor A
lcsh:Diseases of the musculoskeletal system
lcsh:Surgery
Mesenchymal Stem Cell Transplantation
Osseointegration
chemistry.chemical_compound
Mice
Calcification, Physiologic
Osteogenesis
medicine
Animals
Bone repair
collagen scaffold
mesenchymal stromal cells
Femur
Bone regeneration
Osteoblasts
Tissue Scaffolds
vascular endothelial growth factor
Osteoid
Mesenchymal stem cell
Mesenchymal Stem Cells
lcsh:RD1-811
medicine.disease
Vascular endothelial growth factor
medicine.anatomical_structure
chemistry
Bone marrow
Collagen
lcsh:RC925-935
Type I collagen
Biomedical engineering
Calcification
- Language
- English
- ISSN
- 1473-2262
The functional repair of large skeletal defects remains a significant challenge to orthopaedic surgeons due to the lack of effective strategies to promote bone regeneration, particularly in the elderly. This study investigated the potential use of bone marrow derived mesenchymal stromal cells (MSC) in a dense collagen scaffold with a bolus dose of vascular endothelial growth factor (VEGF) to repair a defect in the femoral diaphysis of mice. MSC isolated from bone marrow of 4-month-old donor mice were seeded in type I collagen gels that were then compressed to form scaffolds with a fibrillar density similar to osteoid. The cells remained metabolically active in scaffolds incubated in vitro for up to 15 days and differentiated into osteoblasts that deposited calcium-phosphate mineral into the scaffold, which was quantified using micro-computed tomographic (micro-CT) imaging. When implanted in a 1 mm x 3 mm unicortical defect the MSC-loaded scaffolds were rapidly mineralised and integrated into host bone with administration of 10 ng of recombinant VEGF injected into the femoral canal at 4 days postoperative. Empty scaffolds and MSC-seeded scaffolds implanted in defects that did not receive a bolus dose of VEGF did not mineralise or integrate with native bone. The approach with MSC, hydrogels and a biologic factor already approved for human use warrants further pre-clinical investigation with a large animal model.