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Angiogenesis is a morphogenic process resulting in the formation of new blood vessels from pre-existing ones, usually in hypoxic micro-environments. The initial steps of angiogenesis depend on robust differentiation of oligopotent endothelial cells into the Tip and Stalk phenotypic cell fates, controlled by NOTCH-dependent cell-cell communication. The dynamics of spatial patterning of this cell fate specification are only partially understood. Here, by combining a controlled experimental angiogenesis model with mathematical and computational analyses, we find that the regular spatial Tip-Stalk cell patterning can undergo an order-disorder transition at a relatively high input level of a pro-angiogenic factor VEGF. The resulting differentiation is robust but temporally unstable for most cells, with only a subset of presumptive Tip cells leading sprout extensions. We further find that sprouts form in a manner maximizing their mutual distance, consistent with a Turing-like model that may depend on local enrichment and depletion of fibronectin. Together, our data suggest that NOTCH signaling mediates a robust way of cell differentiation enabling but not instructing subsequent steps in angiogenic morphogenesis, which may require additional cues and self-organization mechanisms. This analysis can assist in further understanding of cell plasticity underlying angiogenesis and other complex morphogenic processes.

As the technologies for treating diseases are attracting continuous attention, physical therapy methods, particularly electrical stimulation (ES), have been widely investigated owing to their high effectiveness. As ES essentially requires an external power source, various efforts are being devoted to achieving the application of ES to the human body using nanogenerators. Various studies have verified the effect of ES by applying the same output generated by the device to in vitro and in vivo bio‐electrical stimulation. However, it is unknown whether the electrical output generated by the device can be transmitted equally in the cell unit, and this is considered a common missing link in bio‐electrical stimulation research. Herein, the missing link between electrical devices and in vitro bio‐electrical stimulations is unraveled by the ex vivo, 2D simulation, and in vitro study of body‐mediated energy transfer (BmET) models. In addition, BmET‐based ES is applied to pre‐osteoblasts, and the increased cellular functions are verified. [ABSTRACT FROM AUTHOR]

In this study, mechanical properties of bioactive glass (BAG) synthetic bone graft substitute was improved by containing ZrO2 (ZrO2‐BAG), while maintaining advantageous biological properties of BAG such as osteoinductive and osteoconductive properties. The ZrO2‐BAG was produced by adding ZrO2 in the following proportions to replace Na2O in 45S5 BAG: 1% (Zr1‐BAG), 3% (Zr3‐BAG), 6% (Zr6‐BAG), and 12% (Zr12‐BAG). Properties including XRD, XPS, SEM, DSC, fracture toughness, and Vickers microhardness were evaluated. To assess the biological properties, Ca/P apatite formation, ion release, degradation rate, cell proliferation, ALP activity (ALP), and alizarin red S staining assay (ARS) were evaluated. Also, expression of osteogenic differentiation markers, Osteopontin (OPN), confirmed by immunofluorescence staining. Finally, an in vivo test was carried out to by implanting ZrO2‐BAG into the subcutaneous tissue of rats. The results of each test were statistically analyzed with one‐way ANOVA followed by Tukey's post hoc statistical test. Amorphous ZrO2‐BAG was successfully produced with increased mechanical properties as the ZrO2 content was increased. Additionally, ZrO2‐BAG exhibited a slower ion release and degradation rate compare to BAG without ZrO2. Bioactivity of ZrO2‐BAG was confirmed with apatite layer formed on the surface, significantly higher proliferation rate and significantly enhanced ALP and the degree of ARS of the cells compare to respective controls. The tissue reactions observed in the in vivo study showed neo‐formed vessels after implantation of ZrO2‐BAG. [ABSTRACT FROM AUTHOR]

Oxygen and nutrients cannot be delivered to cells residingin theinterior of large-volume scaffolds via diffusion alone. Several effortshave been made to meet the metabolic needs of cells in a scaffoldby constructing mass transport channels, particularly in the formof bifurcated networks. In contrast to progress in fabrication technologies,however, an approach to designing an optimal network based on experimentalevaluation has not been actively reported. The main objective of thisstudy was to establish a procedure for designing an effective microfluidicnetwork system for a cell-seeded scaffold and to develop an experimentalmodel to evaluate the design. We proposed a process to design a microfluidicnetwork by combining an oxygen transport simulation with biomimeticprinciples governing biological vascular trees. The simulation wasperformed with the effective diffusion coefficient (De,s), which was experimentally measured in our previousstudy. Porous scaffolds containing an embedded microfluidic networkwere fabricated using the lost mold shape-forming process and saltleaching method. The reliability of the procedure was demonstratedby experiments using the scaffolds. This approach established a practicalbasis for designing an effective microfluidic network in a cell-seededscaffold. [ABSTRACT FROM AUTHOR]

The repertory of neurons generated by progenitor cells depends on their location along antero-posterior and dorso-ventral axes of the neural tube. To understand if recreating those axes was sufficient to specify human brain neuronal diversity, we designed a mesofluidic device termed Duo-MAPS to expose induced pluripotent stem cells (iPSC) to concomitant orthogonal gradients of a posteriorizing and a ventralizing morphogen, activating WNT and SHH signaling, respectively. Comparison of single cell transcriptomes with fetal human brain revealed that Duo-MAPS-patterned organoids generated the major neuronal lineages of the forebrain, midbrain, and hindbrain. Morphogens crosstalk translated into early patterns of gene expression programs predicting the generation of specific brain lineages. Human iPSC lines from six different genetic backgrounds showed substantial differences in response to morphogens, suggesting that interindividual genomic and epigenomic variations could impact brain lineages formation. Morphogen gradients promise to be a key approach to model the brain in its entirety.

In this study, mechanical properties of bioactive glass (BAG) synthetic bone graft substitute was improved by containing ZrO 2 (ZrO 2 -BAG), while maintaining advantageous biological properties of BAG such as osteoinductive and osteoconductive properties. The ZrO 2 -BAG was produced by adding ZrO 2 in the following proportions to replace Na 2 O in 45S5 BAG: 1% (Zr1-BAG), 3% (Zr3-BAG), 6% (Zr6-BAG), and 12% (Zr12-BAG). Properties including XRD, XPS, SEM, DSC, fracture toughness, and Vickers microhardness were evaluated. To assess the biological properties, Ca/P apatite formation, ion release, degradation rate, cell proliferation, ALP activity (ALP), and alizarin red S staining assay (ARS) were evaluated. Also, expression of osteogenic differentiation markers, Osteopontin (OPN), confirmed by immunofluorescence staining. Finally, an in vivo test was carried out to by implanting ZrO 2 -BAG into the subcutaneous tissue of rats. The results of each test were statistically analyzed with one-way ANOVA followed by Tukey's post hoc statistical test. Amorphous ZrO 2 -BAG was successfully produced with increased mechanical properties as the ZrO 2 content was increased. Additionally, ZrO 2 -BAG exhibited a slower ion release and degradation rate compare to BAG without ZrO 2 . Bioactivity of ZrO 2 -BAG was confirmed with apatite layer formed on the surface, significantly higher proliferation rate and significantly enhanced ALP and the degree of ARS of the cells compare to respective controls. The tissue reactions observed in the in vivo study showed neo-formed vessels after implantation of ZrO 2 -BAG., (© 2020 Wiley Periodicals LLC.)

The purpose of this study was to evaluate the change in the retentive forces of four different titanium-based implant attachment systems during the simulation of insert-removal cycles in an artificial oral environment. Five types of titanium-based dental implant attachment systems (Locator, Kerator, O-ring, EZ-Lock, and Magnetic) were studied (n = 10). The specimens underwent insert-removal cycles in artificial saliva, and the retentive force was measured following 0, 750, 1500, and 2250 cycles. Significant retention loss was observed in all attachment systems, except the magnetic attachments, upon completion of 2250 insertion and removal cycles, compared to the initial retentive force ( p < 0.05). A comparison of the initial retentive forces revealed the highest value for Locator, followed by the Kerator, O-ring, EZ-Lock, and Magnetic attachments. Furthermore, Kerator demonstrated the highest retentive loss, followed by Locator, O-ring, EZ-Lock, and Magnetic attachments after 2250 cycles ( p < 0.05). In addition, the Locator and Kerator systems revealed significant decrease in retentive forces at all measurement points ( p < 0.05). The retention force according to the insert-removal cycles were significantly different according to the types of dental implant attachment systems.