Engineered multicomponent bioink enables neuronal maturation and activity in brain-like tissue models

Recreating the physico-mechanical complexities of brain tissue remains a major challenge when engineering neural tissue. Conventional 2D cultures fail to capture the cellular architecture and dynamic environment of the brain while being labor-intensive and low-throughput, motivating the use of 3D bioprinting to generate more physiologically relevant models. In this research article, we introduce a tunable multicomponent bioink composed of alginate, fibrinogen, and aldehyde hyaluronic acid that supports bioprinting of human-induced pluripotent stem-derived neural progenitor cells. We tuned the mechanical and physical properties to optimize printability, stability, and cell-matrix interactions by varying polymer ratios. Optimized constructs exhibited brain-like stiffness, supported long-term cell survival, and promoted neuronal differentiation, neurite extension, and synaptic marker expression over 4 weeks. This reproducible platform offers a scalable approach for creating neural architectures with interconnected networks and coordinated calcium activity and shows promise to be explored for applications such as neurodegenerative disease modeling and preclinical neurotherapeutic discovery.