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Numerous studies have indicated that nano-titanium dioxide (TiO 2 ) can induce neurotoxicity in vitro and in vivo , however, it is unclear whether nano-TiO 2 affects neurite outgrowth of hippocampal neurons. In order to investigate the mechanism of neurotoxicity, rat primary cultured hippocampal neurons on the fourth day of culture were exposed to 5, 15, and 30 μg/mL nano-TiO 2 for 24 h, and nano-TiO 2 internalization, dendritic growth, glutamate metabolism, expression of N-methyl- d -aspartate (NMDA) receptor subunits (NR1, NR2A and NR2B), calcium homeostasis, sodium current (I Na ) and potassium current (I K ) were examined. Our findings demonstrated that nano-TiO 2 crossed the membrane into the cytoplasm or nucleus, and significantly suppressed dendritic growth of primary cultured hippocampal neurons in a concentration-dependent manner. Furthermore, nano-TiO 2 induced a marked release of glutamate to the extracellular region, decreased glutamine synthetase activity and increased phosphate-activated glutaminase activity, elevated intracellular calcium ([Ca 2+ ]i), down-regulated protein expression of NR1, NR2A and NR2B, and increased the amplitudes of the I Na and I K . In addition, nano-TiO 2 increased nitric oxide and nitrice synthase, attenuated the activities of Ca 2+ -ATPase and Na + /K + -ATPase, and increased the ADP/ATP ratio in the primary neurons. Taken together, these findings indicate that nano-TiO 2 inhibits neurite outgrowth of hippocampal neurons by interfering with glutamate metabolism and impairing NMDA receptor function. [ABSTRACT FROM AUTHOR]

Tooth root supports dental crown and bears occlusal force. While proper root shape and size render the force being evenly delivered and dispersed into jawbone. Yet it remains unclear what shape and size of a biological tooth root (bio-root), which is mostly determined by the scaffold geometric design, is suitable for stress distributing and mastication performing. Therefore, this study hypothesized scaffold fabricated in proper shape and size is better for regeneration of tooth root with approving biomechanical functional features. In this study, we optimized shape and size of scaffolds for bio-root regeneration using computer aided design (CAD) modeling and finite element analysis (FEA). Statical structural analysis showed the total deformation (TD) and equivalent von-mises stress (EQV) of the restored tooth model mainly concentrated on the scaffold and the post, in accordance with the condition in a natural post restored tooth. Design sensitivity analysis showed increasing the height and upper diameter of the scaffold can tremendously reduce the TD and EQV of the model, while increasing the bottom diameter of scaffold can, to some extent, reduce the EQV in post. However, increase on post height had little influence on the whole model, only slightly increased the native EQV stress in post. Through response surface based optimization, we successfully screened out the optimal shape of the scaffold used in tissue engineering of tooth root. The optimal scaffold adopted a slightly tapered shape with the upper diameter of 4.9 mm, bottom diameter of 3.4 mm; the length of the optimized scaffold shape was 9.4 mm. While the analysis also suggested a height of about 9 mm for a metal post with a diameter of 1.4 mm suitable for crown restoration in bio-root regeneration. In order to validate the physiological function of the shape optimized scaffold in vivo , we transplanted the shape optimized treated dentin matrix (TDM) scaffold, seeding with dental stem cells, into alveolar bone of swine and further installed porcelain crown. Results showed that tooth root has not only been successfully regenerated histologically but also performed masticatory function and maintained stable for three months after crown restoration. Our results suggested that TDM scaffold with 9.4 mm in length and 4.9 mm/3.4 mm in upper/bottom diameter is a suitable biological scaffold for tooth root regeneration. These results also provided a recommendable design protocol for fabricating other scaffolds in tooth root reconstruction. [ABSTRACT FROM AUTHOR]

Abstract: An essential aspect of tooth tissue engineering is the identification of suitable scaffolding materials to support cell growth and tissue regeneration. Treated dentin matrix (TDM) from a rat has recently been shown to be a suitable scaffold for rat dentin regeneration. However, due to species-specific differences, it remains unclear whether a similar fabrication method can be extended to human TDM and human dentin regeneration. Therefore, this present study explored the biological response to a human TDM (hTDM) created using a modified dentin treatment method. Various biological characteristics, including cell proliferation, cell migration, cell viability, and cytotoxity were investigated. To assess the inductive capacity of hTDM, dental follicle cells (DFCs) were combined with hTDM and were implanted in vivo for 8 weeks in a mouse model. The resulting grafts were studied histologically. The results showed hTDM released dentinogenic factors, indicating that hTDM could play a sustained role in odontogenesis. DFC attachment, growth, viability, and cytotoxicity on the surface of hTDM showed a notable improvement over those on calcium phosphate controls. Most importantly, in vivo hTDM induced and supported regeneration of complete dentin tissues, which expressed dentin markers DSP and DMP-1. As cells in and around the regenerated dentin were positive for human mitochondria, implanted DFCs and hTDM were responsible for the regenerated dentin tissues. In conclusion, hTDM is indicated as an ideal biomaterial for human dentin regeneration. [Copyright &y& Elsevier]