Biological Applications

Functional in vitro models of neural networks are essential for uncovering the underlying cellular mechanisms by which mechanical stress induces traumatic brain injury. However, current models do not capture the connectivity and organization of the brain’s axonal tracts, limiting our ability to study how cellular dysfunction may be transmitted between distant regions of the brain. These models are inadequate due to insufficient fabrication techniques for consistently and accurately placing neurons in a network. Here, we propose a novel method for neural network fabrication that incorporates microfluidic cell placement onto micropatterned substrates. We fabricated a microfluidic device featuring cell traps that capture cells in an organized array, placing them in contact with a fibronectin-coated surface that provides guidance cues for network self-organization. As proof of concept, we used 3T3 fibroblasts to assess the efficiency of this technique. Compared to standard microcontact printing, microfluidic delivery of cells resulted in more consistent, uniform adherence of cells to patterned substrates. Development of this technique may allow fabrication of more authentic neural networks and provide a platform by which we may further investigate the role of diffuse axonal injury in the pathophysiological response to traumatic brain injury.