Creating an environment that mimics the dimensionality and complexity of tissue in the nervous system that can respond to mechanical stimuli to determine injury, responses, and rehabilitation timelines could provide an advance in physiologically relevant systems. One exciting approach toward this is to focus on the mechanobiology perspective merged with a 3D nerve integrated tissue on a chip system, which could potentially aid in the development of protocols and severity assessment of injuries to the brain. Current in vitro 2D systems, while having made great progress over the last decade, are limited by 2D cell-extracellular matrix interactions, which restricts the establishment of a microenvironment comparable to that of 3D neuronal network in the brain. Here we describe an experimental 3D biomaterial in which variational loads and rates are applied to the lab on a chip. Biomaterials, such as collagen, provide a biocompatible, non-toxic ECM to model the brain induced with trauma. We labelled the cells with Fluo-4-AM to examine their calcium response under mechanical stimulation. We imposed mechanical stimulation synchronized with image capturing to examine the cellular response. We observed an increase in calcium during stimulation which was related to strain rate. 

3D in vitro neuron on a chip for probing calcium mechanostimulation

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