• 3d-printed chip
• amyotrophic lateral sclerosis
• assembloids
• axonal connectivity
• connectoids
• cortical organoids
• corticospinal tract
• in vitro modeling
• microfluidic devices
• motor neuron
• neural development
• neuroregeneration
• pdms
• spinal cord injury
• spinal organoids

This thesis aims to model the human corticospinal tract (CST) using cortical organoids (hCOs) and spinal cord organoids (hSpOs) derived from human iPSCs. Two complementary strategies were employed: (1) contact-based fusion of hCOs and hSpOs to form cortico-spinal assembloids, and (2) connectoid-based modeling using microfluidic chips to study long-range axonal connectivity. The spinal organoids were developed using an accelerated protocol and validated by the expression of motor neuron markers, while cortical organoids were assessed for layer-specific neuronal identity. Connectivity was evaluated across different microdevice platforms, including a custom 3D-printed chip (MED160), agarose-based systems, and PDMS microfluidic devices. Together, these models provide an in vitro platform to investigate CST development, axonal guidance, and applications in regeneration and disease modeling.