Engineering in vitro human neural tissue analogs by 3D bioprinting and electrostimulation

There is a fundamental need for clinically relevant, reproducible, and standardized in vitro human neural tissue models, not least of all to study heterogenic and complex human-specific neurological (such as neuropsychiatric) disorders. Construction of three-dimensional (3D) bioprinted neural tissues from native human-derived stem cells (e.g., neural stem cells) and human pluripotent stem cells (e.g., induced pluripotent) in particular is appreciably impacting research and conceivably clinical translation. Given the ability to artificially and favorably regulate a cell's survival and behavior by manipulating its biophysical environment, careful consideration of the printing technique, supporting biomaterial and specific exogenously delivered stimuli, is both required and advantageous. By doing so, there exists an opportunity, more than ever before, to engineer advanced and precise tissue analogs that closely recapitulate the morphological and functional elements of natural tissues (healthy or diseased). Importantly, the application of electrical stimulation as a method of enhancing printed tissue development in vitro, including neuritogenesis, synaptogenesis, and cellular maturation, has the added advantage of modeling both traditional and new stimulation platforms, toward improved understanding of efficacy and innovative electroceutical development and application.