Abstract
Numerous studies have demonstrated that Schwann cells (SCs) play a role in nerve regeneration; however, their role in innervating a bioceramic scaffold for potential application in bone regeneration is still unknown. Here we report the cell growth and functional behavior of SCs on β-tricalcium phosphate (β-TCP) scaffolds arranged in 3D printed-lattice (P-β-TCP) and randomly-porous, template-casted (N-β-TCP) structures. Our results indicate that SCs proliferated well and expressed the phenotypic markers p75LNGFR and the S100-β subunit of SCs as well as displayed growth morphology on both scaffolds, but SCs showed spindle-shaped morphology with a significant degree of SCs alignment on the P-β-TCP scaffolds, seen to a lesser degree in the N-β-TCP scaffold. The gene expressions of nerve growth factor (β-ngf), neutrophin–3 (nt–3), platelet-derived growth factor (pdgf-bb), and vascular endothelial growth factor (vegf-a) were higher at day 7 than at day 14. While no significant differences in protein secretion were measured between these last two time points, the scaffolds promoted the protein secretion at day 3 compared to that on the cell culture plates. These results together imply that the β-TCP scaffolds can support SC cell growth and that the 3D-printed scaffold appeared to significantly promote the alignment of SCs along the struts. Further studies are needed to investigate the early and late stage relationship between gene expression and protein secretion of SCs on the scaffolds with refined characteristics, thus better exploring the potential of SCs to support vascularization and innervation in synthetic bone grafts.
Highlights
The key challenge of bone tissue regeneration using ceramic scaffolds is still insufficient vascularization [1,2]
Porosity of the N-β-tricalcium phosphate (β-TCP) and Pβ-TCP scaffolds was measured at 79.2±2.3% and 42.3±6.7%, respectively
This study demonstrated that β-TCP scaffolds support the growth of Schwann cells (SCs) and normal nerverelated cell morphologies
Summary
The key challenge of bone tissue regeneration using ceramic scaffolds is still insufficient vascularization [1,2]. While many strategies are being developed, one avenue that has not been extensively explored in bone graft engineering is the incorporation of nervous system glia and their potential role in bone tissue regeneration. Throughout the body, nerves and blood vessels run in parallel. Even in cases where nerves have been intentionally made to misalign, blood vessels will still follow the defective nerve pathway [3]. This suggests a significant role of the nervous system in angiogenesis [4,5,6], which is pertinent due to angiogenesis’s key role in osteogenesis [7]. SCs are already widely known to provide innervation to grafts through their role in peripheral nerve repair [10,11,12], and significant angiogenic inducing potential through growth factor secretion [13]
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