Abstract
BackgroundTissue engineering approaches for reconstruction of large bone defects are still technically immature, especially in regard to sufficient blood supply. Therefore, the aim of the present study was to investigate the influence of osteogenic stimulation and treatment with VEGF on new bone formation and neovascularization in hMSC-loaded cancellous bone scaffolds in vivo.MethodsCubic scaffolds were seeded with hMSC and either cultured in stem cell medium or osteogenic stimulation medium. One osteogenically stimulated group was additionally treated with 0.8 μg VEGF prior to subcutaneous implantation in athymic mice. After 2 and 12 weeks in vivo, constructs and selected organs were harvested for histological and molecular analysis.ResultsHistological analysis revealed similar vascularization of the constructs with and without VEGF treatment and absence of new bone formation in any group. Human DNA was detected in all inoculated scaffolds, but a significant decrease in cells was observed after 2 weeks with no further decrease after 12 weeks in vivo.ConclusionUnder the chosen conditions, osteogenic stimulation and treatment with VEGF does not have any influence on the new bone formation and neovascularization in hMSC-seeded cancellous bone scaffolds.Electronic supplementary materialThe online version of this article (doi:10.1186/1471-2474-15-350) contains supplementary material, which is available to authorized users.
Highlights
Tissue engineering approaches for reconstruction of large bone defects are still technically immature, especially in regard to sufficient blood supply
One promising approach is the use of growth factors such as vascular endothelial growth factor (VEGF), which plays an important role in inducing neovascularization and bone healing [3]
Beside the improved blood supply, this phenomenon could be ascribed to the VEGF-triggered bilateral communication between endothelial and osteogenic cell lineages leading to a broad proliferation of endothelial cells and differentiation of osteogenic progenitor cells into osteoblasts [5,6]
Summary
Tissue engineering approaches for reconstruction of large bone defects are still technically immature, especially in regard to sufficient blood supply. The aim of the present study was to investigate the influence of osteogenic stimulation and treatment with VEGF on new bone formation and neovascularization in hMSC-loaded cancellous bone scaffolds in vivo. Tissue engineering approaches for reconstruction of such bone defects are appealing, but to date technically insufficient. In this context, one major problem – the blood supply during the first days in vivo – remains unsolved. Kaigler et al reported on significantly increased vascular perfusion and bone formation in irradiated osseous defects using VEGF-releasing polymer scaffolds [4]. Beside the improved blood supply, this phenomenon could be ascribed to the VEGF-triggered bilateral communication between endothelial and osteogenic cell lineages leading to a broad proliferation of endothelial cells and differentiation of osteogenic progenitor cells into osteoblasts [5,6]
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