Developing a bioprinted scaffold‐based model of neurodegeneration for high throughput screening in Drug Development

Abstract Background A major component of the failure to bring novel drugs for Alzheimer’s disease (AD) to market is the translational gap between in vitro , animal and human studies. Using the novel technology of 3D bio‐printing, this project aims to develop a scaffold‐based 3D quad‐culture model of AD for drug screening using human induced pluripotent stem cells. Method A cell‐hydrogel suspension is “printed” onto 96‐ and 394‐well plates using a 3D bioprinter, which uses drop‐on‐demand technology to allow high resolution placement of the cells. The culture is suspended in a hydrogel of extracellular matrix proteins, which has been modulated to mimic brain biomechanics. Result Protocols to differentiate human neural progenitor cells into cortical neurons, astrocytes and oligodendrocytes have been established from AD mutation lines and healthy controls which express desired markers. These cell types, alongside iPSC‐derived microglia, will form the quad‐culture of cells within the model. Conclusion This model will exercise the benefits of a 3D model, while maintaining the benefits of 2D systems, including reproducibility, reliability, and suitability for high throughput screening.