Understanding, engineering, and modulating the growth of neural networks: An interdisciplinary approach.

A deeper understanding of the brain and its function remains one of the most significant scientific challenges. It not only is required to find cures for a plethora of brain-related diseases and injuries but also opens up possibilities for achieving technological wonders, such as brain-machine interface and highly energy-efficient computing devices. Central to the brain's function is its basic functioning unit (i.e., the neuron). There has been a tremendous effort to understand the underlying mechanisms of neuronal growth on both biochemical and biophysical levels. In the past decade, this increased understanding has led to the possibility of controlling and modulating neuronal growth in vitro through external chemical and physical methods. We provide a detailed overview of the most fundamental aspects of neuronal growth and discuss how researchers are using interdisciplinary ideas to engineer neuronal networks in vitro . We first discuss the biochemical and biophysical mechanisms of neuronal growth as we stress the fact that the biochemical or biophysical processes during neuronal growth are not independent of each other but, rather, are complementary. Next, we discuss how utilizing these fundamental mechanisms can enable control over neuronal growth for advanced neuroengineering and biomedical applications. At the end of this review, we discuss some of the open questions and our perspectives on the challenges and possibilities related to controlling and engineering the growth of neuronal networks, specifically in relation to the materials, substrates, model systems, modulation techniques, data science, and artificial intelligence.