Toward a neurospheroid niche model: optimizing embedded 3D bioprinting for fabrication of neurospheroid brain-like co-culture constructs.

A crucial step in creating reliablein vitroplatforms for neural development and disorder studies is the reproduction of the multicellular three-dimensional (3D) brain microenvironment and the capturing of cell-cell interactions within the model. The power of self-organization of diverse cell types into brain spheroids could be harnessed to study mechanisms underlying brain development trajectory and diseases. A challenge of current 3D organoid and spheroid models grown in petri-dishes is the lack of control over cellular localization and diversity. To overcome this limitation, neural spheroids can be patterned into customizable 3D structures using microfabrication. We developed a 3D brain-like co-culture construct using embedded 3D bioprinting as a flexible solution for composing heterogenous neural populations with neurospheroids and glia. Specifically, neurospheroid-laden free-standing 3D structures were fabricated in an engineered astrocyte-laden support bath resembling a neural stem cell niche environment. A photo-crosslinkable bioink and a thermal-healing supporting bath were engineered to mimic the mechanical modulus of soft tissue while supporting the formation of self-organizing neurospheroids within elaborate 3D networks. Moreover, bioprinted neurospheroid-laden structures exhibited the capability to differentiate into neuronal cells. These brain-like co-cultures could provide a reproducible platform for modeling neurological diseases, neural regeneration, and drug development and repurposing.

Carbon Nanotubes in Biomedical Applications: Factors, Mechanisms, and Remedies of Toxicity.

Carbon nanotubes (CNTs) represent one of the most studied allotropes of carbon. The unique physicochemical properties of CNTs make them among prime candidates for numerous applications in biomedical fields including drug delivery, gene therapy, biosensors, and tissue engineering applications. However, toxicity of CNTs has been a major concern for their use in biomedical applications. In this review, we present an overview of carbon nanotubes in biomedical applications; we particularly focus on various factors and mechanisms affecting their toxicity. We have discussed various parameters including the size, length, agglomeration, and impurities of CNTs that may cause oxidative stress, which is often the main mechanism of CNTs' toxicity. Other toxic pathways are also examined, and possible ways to overcome these challenges have been discussed.