Melissa Andrea Cadena
BME PhD Defense Presentation

Date: 2025-04-23
Time: 1:00 PM
Location / Meeting Link: HSRBII N600 / https://emory.zoom.us/j/92731575618

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 Organoids to Create a Tunable Platform for Modeling Human Neurodevelopment

Abstract:
In vitro models of the human nervous system are crucial for understanding the mechanisms that choreograph neural 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 non-human animal models to address these questions. While useful, many animal models lack the full cellular repertoire, neurophysiology, and structural architecture of human central nervous system development. 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 be patterned to replicate varying regions of the nervous system, 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 to these in vitro models. First, the lack of functional vasculature within organoids may cause necrosis and/or hypoxia and limits the ability to investigate vasculature-neural ectoderm interactions. In addition, the absence of morphogen gradients, which in vivo drive patterning across different brain regions, limits cell type diversity and prevents the study of inter-regional brain interactions. To address these limitations, we integrated 3D bioprinting with cortical brain organoids to create a tunable culturing platform that more accurately recapitulates aspects of human brain development. We achieved this by (i) developing and characterizing 3D bioprinted microchanneled gelatin methacrylate (GelMA) scaffolds for the long-term culture of organoids, (ii) demonstrating that our platform supports the co-culture of endothelial cells and cortical organoids, and (iii) incorporating closed-loop perfusion into our vascularized scaffolds to introduce functional flow. This work addressed key limitations of conventional brain organoid models and established a more robust, modular system for studying human neurodevelopment in vitro.