3D bioprinted functional neural tissue models of the central nervous system using a chitosan-based bioink

The intricate architecture of the human central nervous system (CNS) presents significant challenges in developing in vitro models that accurately recapitulate its functionality. Traditional two-dimensional neuronal cultures lack the spatial complexity required to mimic the cellular organization and brain architecture. Advances in neural tissue engineering have led to the emergence of three-dimensional (3D) tissue-engineered brain models. Bioprinting technologies are promising approaches that are increasingly used to deliver cells, biomaterials, and biological factors to recreate various stratified brain tissue regions. In this work, a novel chitosan-based thermogel bioink was formulated to support the embedding of different neural cells. The rheological and mechanical properties of the bioink were characterized, and the printing protocol was optimized to ensure efficient bioink deposition, resulting in personalized patterned models with good print resolution and shape fidelity. The bioprinted constructs exhibited geometric fidelity and sustained high levels of cellular viability, creating an environment conducive to the development of functional neuronal networks derived from human-induced pluripotent stem cells (hiPSCs) co-cultured with astrocytes. Preliminary electrophysiological assessments conducted with high-density microelectrode arrays (HD-MEAs) demonstrated evidence of functional activity within the networks. This approach mimics the spatial and functional organization of brain tissue in vitro, offering a valuable tool for advancing neural tissue modelling to study neural behaviour and interactions.