A 3D Bioprinted model to examine the effect of stiffness on cortical organoids
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Sridhar, Vani
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Abstract
The human brain development is an intricate, dynamic, and highly regulated process that begins in the prenatal period and continues through adulthood. This process involves several complex mechanisms including differentiation, proliferation, migration, and maturation of neural progenitor cells into various types of neurons and glial cells, forming the intricate neural circuits that underlie cognition, behavior, and sensory processing. Intensive study of the neurobiology of brain development is essential because of its direct impact on human behavior and furthermore, to fully understand the pathophysiology and etiology of neurodevelopmental disorders (NDDs), which in turn are disruptive to human brain development. Due to the obvious limitation of studying a developing human brain, researchers rely on bioengineered in vitro models to accurately recapitulate the physiological conditions of brain tissue.
Current bioengineering efforts encompass using biomaterials and stem cells to establish the models, incorporate vasculature, and induce the necessary physical and chemical cues using external additives and factors. One such extracellular matrix (ECM) cue of high importance is the mechanical stiffness (i.e., elastic modulus) of the tissue. The brain is one of the softest tissues in our body; although, as the brain tissue matures, its stiffness gradually increases. This study aims to investigate the effect of varying stiffnesses on human cortical organoids in a 3D bioprinted hydrogel model. The organoids are embedded into these models and co-cultured with endothelial cells. At different time points, the cell viability, growth, and other developmental markers were studied to assess the contribution of ECM stiffness to the developing brain.
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2024-04-29
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