Tumor-on-a-chip: Perfusable vascular incorporation brings new approach to tumor metastasis research and drug development.

The extracellular matrix interacts with cancer cells and is a key factor in the development of cancer. Traditional two-dimensional models cannot mimic the natural in situ environment of cancer tissues, whereas three-dimensional (3D) models such as spherical culture, bioprinting, and microfluidic approaches can achieve in vitro reproduction of certain structures and components of the tumor microenvironment, including simulation of the hypoxic environment of tumor tissue. However, the lack of a perfusable vascular network is a limitation of most 3D models. Solid tumor growth and metastasis require angiogenesis, and tumor models with microvascular networks have been developed to better understand underlying mechanisms. Tumor-on-a-chip technology combines the advantages of microfluidics and 3D cell culture technology for the simulation of tumor tissue complexity and characteristics. In this review, we summarize progress in constructing tumor-on-a-chip models with efficiently perfused vascular networks. We also discuss the applications of tumor-on-a-chip technology to studying the tumor microenvironment and drug development. Finally, we describe the creation of several common tumor models based on this technology to provide a deeper understanding and new insights into the design of vascularized cancer models. We believe that the tumor-on-a-chip approach is an important development that will provide further contributions to the field.

Vibration loading promotes osteogenic differentiation of bone marrow-derived mesenchymal stem cells via p38 MAPK signaling pathway.

Low magnitude high frequency vibration (LMHFV) exhibits effectively anabolic effects on the bone tissue, and can promote osteogenic differentiation of mesenchymal stem cells (MSCs) in vitro. The role of p38 MAPK signaling in LMHFV-induced osteogenesis remains unclear. In this current study, LMHFV loading was applied to BMSCs in vitro, and cell proliferation, alkaline phosphatase (ALP), matrix mineralization, as well as osteogenic genes expression were assayed. The mechanism of mechanical signal transduction was analysed using PCR array, qRT-PCR and Western blot. LMHFV increased cell proliferation in the growth medium, while inhibited proliferation in the osteogenic medium. ALP activity, matrix mineralization and osteogenic genes expression of Runx2, Col-I, ALP, OPN and OC were increased by LMHFV. p38 and MKK6 genes expression, and p38 phosphorylation were promoted in LMHFV-induced osteogenesis. Inhibition of p38 MAPK with SB203580 and targeted p38 siRNA blunted the increased ALP activity and osteogenic genes expression by LMHFV. These findings suggest that LMHFV promotes osteogenic differentiation of BMSCs, and p38 MAPK signaling shows an important function in LMHFV-induced osteogenesis.

Promotion of enamel caries remineralization by an amelogenin-derived peptide in a rat model.

OBJECTIVE: An amelogenin-derived peptide has been shown to promote remineralization of demineralized enamel in an in vitro model of initial caries induced by pH cycling. The present study examines whether the peptide exerts similar effects within the complex oral environment in vivo. DESIGN: Specific pathogen-free Sprague-Dawley rats (n=36) were infected with Streptococcus mutans, given ad libitum access to Diet 2000 and drinking water supplemented with sucrose (10%, w/v), and then randomly divided into three groups treated with 25µM peptide solution, 1g/L NaF or deionized water. Molar teeth were swabbed twice daily with the respective solutions for 24days. Then animals were killed, their jaws were removed and caries lesions were analyzed using the quantitative light-induced fluorescence-digital (QLF-D) technique to measure changes in mineral content. To verify QLF-D results, caries were scored for lesion depth and size using the Keyes method, and analyzed using polarized light microscopy (PLM). RESULTS: Mineral gain was significantly higher in teeth treated with peptide or NaF than in teeth treated with water (p<0.05), based on the QLF-D results (ΔF and ΔQ). Incidence of smooth-surface and sulcal caries based on Keyes scores was similar in rats treated with peptide or NaF, and significantly lower in these groups than in rats treated with water (p<0.05). Lesions on teeth treated with peptide or NaF were shallower, based on PLM. No significant differences were observed between molar enamel caries treated with peptide or NaF. CONCLUSIONS: This amelogenin-derived peptide can promote remineralization in a rat caries model, indicating strong potential for clinical use.

Potential of an amelogenin based peptide in promoting reminerlization of initial enamel caries.

OBJECTIVE: In this study we give a preliminary study of a rationally designed small peptide, which is based on the enamel matrix protein amelogenin, to investigate its effect on remineralization of initial enamel caries lesions. DESIGN: A novel peptide was designed and synthesized to investigate its effects on the remineralization of initial enamel carious lesions during pH cycling that simulates intra-oral conditions. Initial lesions were created in bovine enamel blocks, which were then pH-cycled for 12 days in the presence of 25µM peptide, 1g/L NaF (positive control), 50mM HEPES buffer(negative control). Before and after pH cycling, enamel blocks were analyzed by surface microhardness testing, polarized light microscopy and transverse microradiography. RESULTS: Percentage of surface microhardness recovery (SMHR%) after pH cycling was significantly higher in peptide group than HEPES group. Lower lesion depth and less mineral mineral loss were found in peptide or NaF treatment groups after the cycling, and were significantly different to HEPES group. No significant differences were observed between the blocks treated with peptide and those treated with NaF. CONCLUSSION: This study provides in vitro evidence that this amelogenin based peptide promotes enamel caries remineralization, offering a promising remineralizing biomaterial in initial enamel carious treatment.