Abstract
Background Angiogenesis is a prerequisite step to achieve the success of bone regeneration by tissue engineering technology. Previous studies have shown the role of cerebrospinal fluid pulsation (CSFP) stress in the reconstruction of tissue-engineered laminae. In this study, we investigated the role of CSFP stress in the angiogenesis of tissue-engineered laminae. Methods For the in vitro study, a CSFP bioreactor was used to investigate the impact of CSFP stress on the osteogenic mesenchymal stem cells (MSCs). For the in vivo study, forty-eight New Zealand rabbits were randomly divided into the CSFP group and the Non-CSFP group. Tissue-engineered laminae (TEL) was made by hydroxyapatite-collagen I scaffold and osteogenic MSCs and then implanted into the lamina defect in the two groups. The angiogenic and osteogenic abilities of newborn laminae were examined with histological staining, qRT-PCR, and radiological analysis. Results The in vitro study showed that CSFP stress could promote the vascular endothelial growth factor A (VEGF-A) expression levels of osteogenic MSCs. In the animal study, the expression levels of angiogenic markers in the CSFP group were higher than those in the Non-CSFP group; moreover, in the CSFP group, their expression levels on the dura mater surface, which are closer to the CSFP stress stimulation, were also higher than those on the paraspinal muscle surface. The expression levels of osteogenic markers in the CSFP group were also higher than those in the Non-CSFP group. Conclusion CSFP stress could promote the angiogenic ability of osteogenic MSCs and thus promote the angiogenesis of tissue-engineered laminae. The pretreatment of osteogenic MSC with a CSFP bioreactor may have important implications for vertebral lamina reconstruction with a tissue engineering technique.
Highlights
Angiogenesis is a prerequisite step to achieve the success of bone regeneration by tissue engineering technology
The IF staining of vascular endothelial growth factor A (VEGF-A) showed that the cerebrospinal fluid pulsation (CSFP)+osteogenic mesenchymal stem cells (MSCs) group had higher vascular endothelial growth factor (VEGF)-A expression (Figure 3)
The live/dead staining showed that almost all the osteogenic MSCs survived 7 days after implantation into hydroxyapatite-collagen I scaffold, and the cells tightly adhered to the trabeculae structure of the scaffold
Summary
Angiogenesis is a prerequisite step to achieve the success of bone regeneration by tissue engineering technology. Previous studies have shown the role of cerebrospinal fluid pulsation (CSFP) stress in the reconstruction of tissue-engineered laminae. We investigated the role of CSFP stress in the angiogenesis of tissue-engineered laminae. For the in vitro study, a CSFP bioreactor was used to investigate the impact of CSFP stress on the osteogenic mesenchymal stem cells (MSCs). CSFP stress could promote the angiogenic ability of osteogenic MSCs and promote the angiogenesis of tissue-engineered laminae. The result revealed that the biological factors released from the bone end could initiate the early onset osteogenesis of the artificial laminae, and the mechanical stimulation of cerebrospinal fluid pulsation (CSFP) stress could promote the osteogenesis and remodeling of the artificial laminae [3, 4]. Mesenchymal stem cells (MSCs) are among the most promising stem cell types for vascular tissue engineering and have been widely used among all the above-mentioned strategies [6, 7, 9], because MSCs can transdifferentiate into all cell lineages of three germ layers including blood vessel cells arising from mesodermal tissue and can secrete a series of angiogenic factors, such as vascular endothelial growth factor (VEGF), Monocyte Chemoattractant
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