Influence of osteogenic stimulation and VEGF treatment on in vivo bone formation in hMSC-seeded cancellous bone scaffolds

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.

Cell‐based strategies for vascular regeneration

“…The in vivo results showed that cell‐seeded bone grafts precultured in osteogenic medium generated higher functional microvascular networks than those precultured in based medium. Interestingly, another study showed the similar neovascularization of BM‐MSC‐seeded bone grafts with or without VEGF treatment . These results further implicated that BM‐MSCs have the ability to secrete VEGF .…”

“…Interestingly, another study showed the similar neovascularization of BM-MSC-seeded bone grafts with or without VEGF treatment. 101 These results further implicated that BM-MSCs have the ability to secrete VEGF. 54,55 Compared with mono-culture system, co-culture of BM-MSCs and ECs (seen in Table II) or EPCs (seen in Table V) have showed the significant improvement of tissue neovascularization in most studies.…”

Microfluidic synthesis of PLGA/carbon quantum dot microspheres for vascular endothelial growth factor delivery

“…[4][5][6][7][8] Moreover, some methods to seed stem cells into the gra materials have been reported, but in these techniques, the cell viability in the deep portion of large scaffolds is compromised as a result of poor vascularization and following hypoxia and inadequate nutrient transport. [9][10][11] In general, problems in functional vascularization lead to a lack of gra integration and the ultimate failure of craniomaxillofacial tissue-engineered products.…”

Advanced Nanostructured Medical Device Combining Mesenchymal Cells and VEGF Nanoparticles for Enhanced Engineered Tissue Vascularization

“…Bone healing can be improved by adjusting the speed of vascularization and during the last 5 years, attempts have been made to increase vascularization in the tissue-engineering field [27-29, 33, 38-39]. Hence, basic strategies using scaffolds focused firstly on the use of cells (HUVEC, EPC) [30][31][32], and secondly on the use of active molecules (VEGF, Ang1, ...) operating on endothelial cells [34][35][36] to promote proliferation, migration, sprouting and establishment of functional blood vessel. In our strategy, we chose to use not only VEGF active molecules (VEGF-NPs), but also endothelial and mesenchymal cells.…”

“…The prosthesis domain aims for replacement after ablation due to severe injuries, the bone substitute domain, targets the substitution of important lesions (until 60 cm [27][28][29]33]. In order to increase vascularization within the implanted site, several active angiogenic materials were developed with majority based on cell activities [34][35][36] or added factors activity [30][31][32]. One of the main growth factor involved in angiogenesis is VEGF165 (Vascular Endothelial Growth Factor) which acts as an initiator and a modulator of the signaling cascade resulting in proliferation and migration of endothelial cells toward formation of new blood vessels [37,38].…”