Engineered Humanized Spinal Cord Construct for Advancing Health and Disease Research

Objective

Current in vitro models of the central nervous system (CNS) fail to recapitulate its intricate structure and function, posing significant challenges to advancing our understanding of neurodevelopmental, neurological, and neurodegenerative diseases. Current 2D cultures, 3D organoids and animal models are limited for studying both healthy and pathological states, slowing progress in neuroscience. New CNS models must integrate advanced biofabrication, innovative bioinks, and cellular engineering to mimic the complex structure, vascular networks, and multi-cellular integration of the CNS. Recent progress in bioprinting and tissue engineering enable the fabrication of complex structures, while bioinks and biomaterials provide optimal cellular environments for differentiation, and functional integration. Additionally, state-of-the-art imaging and omic technologies have improved the ability to capture detailed structural and cellular data, ensuring that CNS models mimic native CNS architecture and dynamics. SPINECRAFT will develop a 4D functional human spinal cord construct (hSCC) that replicates the structural complexity and dynamic functionality of the human spinal cord (hSC). Our approach will use advanced imaging and computational techniques to map the architecture and cell distribution of the hSC. Using this information, we will generate human neural and vascular cells alongside bioinks designed to mimic the native microenvironment. We will then print a high-fidelity hSCC, validate it with imaging, multi-omics, and electrophysiology, and integrate patient-specific iPSCs to model amyotrophic lateral sclerosis (ALS) to recapitulate disease-specific microenvironments. SPINECRAFT represents a paradigm shift in CNS research, providing a versatile platform to study hSC biology, neurodegenerative diseases, and regenerative therapies. This integrative approach will raise the standards of tissue engineering and drive technological advances beyond spinal cord applications.