3D Printing Hydrogel Vasculature and Bioactive Cues within Brain Organoids

PROJECT SUMMARY Brain organoids hold great potential for understanding neurodevelopmental and neurodegenerative diseases. However, their utility is constrained by several factors including necrotic core formation, immaturity, and high variability. This project aims to develop a robust and reproducible in vitro method for growing brain organoids with improved structural complexity, cellular diversity, and long-term viability. Additionally, it seeks to gain biological insights into how substrate stiffness, perfusion, and neural peptides affect brain organoid growth, maturation, and function. The project will utilize 3D printing to create vascular-like networks using synthetic multidomain peptide (MDP) hydrogels within the interior of brain organoids, while also providing brain-specific mechanical and peptide signaling cues. The first aim of the project is to investigate how the stiffness of MDP hydrogels impacts the growth and function of organoids grown around the hydrogel. The second aim involves using a 3D printed hydrogel vasculature within the organoids to determine whether perfusion through this vascular network prevents necrotic core formation. The third aim focuses on incorporating neural peptide cues into the MDP hydrogels and exploring their effects on improving cellular diversity and maturation within the brain organoids. The findings from this project will guide the development of a novel method for growing brain organoids in a reproducible and physiologically relevant manner, enhancing their utility for the study of neurodevelopmental and neurodegenerative diseases. The long-term objective is to establish robust methods for growing brain organoids that more closely mimic the human brain, offering a valuable platform for therapeutic development and disease modeling. Research will be conducted at the Salk Institute for Biological Studies and under the mentorship from Dr. Fred Gage. This project will utilize a range of quantitative neuroscience technologies and offer valuable training opportunities.