Biomimetic three-dimensional glioma model printed in vitro for the studies of glioma cells and neurons interactions

The interactions between glioma cells and neurons are important for glioma progression but are rarely mimicked and recapitulated in in vitro three-dimensional (3D) models, which may affect the success rate of relevant drug research and development. In this study, an in vitro bioprinted 3D glioma model consisting of an outer hemispherical shell with neurons and an inner hemisphere with glioma cells is proposed to simulate the natural glioma. This model was produced by extrusion-based 3D bioprinting technology. The cells survival rate, morphology, and intercellular Ca2+ concentration studies were carried out up to 5 days of culturing. It was found that neurons could promote the proliferation of glioma cells around them, associate the morphological changes of glioma cells to be neuron-like, and increase the expression of intracellular Ca2+ of glioma cells. Conversely, the presence of glioma cells could maintain the neuronal survival rate and promote the neurite outgrowth. The results indicated that glioma cells and neurons facilitated each other implying a symbiotic pattern established between two types of cells during the early stage of glioma development, which were seldom found in the present artificial glioma models. The proposed bioprinted glioma model can mimic the natural microenvironment of glioma tissue, provide an in-depth understanding of cellâ cell interactions, and enable pathological and pharmacological studies of glioma.The work was supported by the Program of the National Natural Science Foundation of China [52275291], [51675411], [81972359], the Fundamental Research Funds for the Central Universities, and the Youth Innovation Team of Shaanxi Universities

Forming Limit Stress Diagram Prediction of Pure Titanium Sheet Based on GTN Model

In this paper, the initial values of damage parameters in the Gurson–Tvergaard–Needleman (GTN) model are determined by a microscopic test combined with empirical formulas, and the final accurate values are determined by finite element reverse calibration. The original void volume fraction (f0), the volume fraction of potential nucleated voids (fN), the critical void volume fraction (fc), the void volume fraction at the final failure (fF) of material are assigned as 0.006, 0.001, 0.03, 0.06 according to the simulation results, respectively. The hemispherical punch stretching test of commercially pure titanium (TA1) sheet is simulated by a plastic constitutive formula derived from the GTN model. The stress and strain are obtained at the last loading step before crack. The forming limit diagram (FLD) and the forming limit stress diagram (FLSD) of the TA1 sheet under plastic forming conditions are plotted, which are in good agreement with the FLD obtained by the hemispherical punch stretching test and the FLSD obtained by the conversion between stress and strain during the sheet forming process. The results show that the GTN model determined by the finite element reverse calibration method can be used to predict the forming limit of the TA1 sheet metal