Autism spectrum disorder (ASD) is a neurodevelopmental disorder characterized by impaired intellectual disabilities and social communication and interactions. The underlying pathology of ASD is not well understood, and there is currently no drug treatment. We aim to create an in vitro 3D ASD model, based on our previously published bioengineered 3D brain tissue model with silk-based scaffolds, using 1) neurons from mouse ASD models for proof-of-concept, and 2) neurons derived from human ASD patients’ induced pluripotent cells. The model will facilitate the investigation of molecular pathways involved in ASD as well as drug discovery.