Melissa Andrea Cadena
BME PhD Proposal Presentation

Date:2022-07-27
Time: 11am-1pm
Location / Meeting Link: Whitehead Biomedical Research Building Room 500/ https://emory.zoom.us/j/96181676007?pwd=bEN2VjkxM3pmdENYUEtFaFgzNjJNZz09

Committee Members:
Steven Sloan, MD/PhD (Co-advisor), Vahid Serpooshan, PhD (Co-advisor), Scott Hollister, PhD, Hang Lu, PhD, Fikri Birey, PhD, Morteza Mahmoudi, PhD


Title: Integrating 3D Bioprinting and Cortical Brain Organoids to Create a Tunable Platform for Modeling Human Neurodevelopment

Abstract:
Human brain development models are crucial for understanding the complex mechanisms that choreograph development and the processes that are disrupted in neurodevelopmental disorders. However, due to limited access to primary tissue at key developmental time points, the field of developmental neurobiology has largely relied on animal models. While useful, animal models lack the full complexity of human central nervous system development and are expensive and time-intensive. The ability to form brain organoids from human induced pluripotent stem cells has provided a reproducible, scalable, and alternate physiological model system to study human brain development. Brain organoids can now be patterned to replicate different brain regions, echo architectural features of the developing human brain, and contain multiple integrated cell types, such as neurons, radial glia, and astrocytes. Yet, there remain key limitations that prevent organoid models from fully recapitulating features of human brain development. First, the lack of functional vasculature within organoids may cause necrosis and/or hypoxia and limits the ability to study vasculature-neural ectoderm interactions. In addition, the absence of morphogen gradients, which in vivo drive the formation of different brain regions, limits cell type diversity and prevents the study of inter-regional brain interactions. To address these limitations, this proposal aims to integrate 3D bioprinting and cortical brain organoids to create a tunable culturing platform that better recapitulates human brain development. This will be achieved by (i) developing and characterizing 3D bioprinted microchanneled gelatin methacrylate scaffolds for the long-term culture of organoids, (ii) incorporating functional vasculature into bioprinted scaffolds and culturing with organoids, and (iii) using multi-material 3D bioprinting to introduce morphogen gradients within the bioprinted scaffold to induce organoid patterning into pallial-subpallial fates. The proposed work will work towards addressing the current limitations of brain organoids and provide a more robust, tunable modeling platform to study human neurodevelopment.