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.

Hypoxia is a typical feature of the tumor microenvironment, one of the most critical factors affecting cell behavior and tumor progression. However, the lack of tumor models able to precisely emulate natural brain tumor tissue has impeded the study of the effects of hypoxia on the progression and growth of tumor cells. This study reports a three-dimensional (3D) brain tumor model obtained by encapsulating U87MG (U87) cells in a hydrogel containing type I collagen. It also documents the effect of various oxygen concentrations (1%, 7%, and 21%) in the culture environment on U87 cell morphology, proliferation, viability, cell cycle, apoptosis rate, and migration. Finally, it compares two-dimensional (2D) and 3D cultures. For comparison purposes, cells cultured in flat culture dishes were used as the control (2D model). Cells cultured in the 3D model proliferated more slowly but had a higher apoptosis rate and proportion of cells in the resting phase (G0 phase)/gap I phase (G1 phase) than those cultured in the 2D model. Besides, the two models yielded significantly different cell morphologies. Finally, hypoxia (e.g., 1% O2) affected cell morphology, slowed cell growth, reduced cell viability, and increased the apoptosis rate in the 3D model. These results indicate that the constructed 3D model is effective for investigating the effects of biological and chemical factors on cell morphology and function, and can be more representative of the tumor microenvironment than 2D culture systems. The developed 3D glioblastoma tumor model is equally applicable to other studies in pharmacology and pathology.