Penn-Engineered Neural Networks Show Hope for Axonal Repair in the Brain, with Minimal Disruption to Brain Tissue

D. Kacy Cullen

Lab-grown neural networks have the ability to replace lost axonal tracks in the brains of patients with severe head injuries, strokes or neurodegenerative diseases and can be safely delivered with minimal disruption to brain tissue, according to new research from Penn Medicine’s department of Neurosurgical Research. Their work is published in the Journal of Neural Engineering.

Complex brain function derives from the activity of populations of neurons – discrete processing centers – connected by long fibrous projections known as axons. When these connections are damaged, by injury or diseases such as a Parkinson’s or Alzheimer’s disease, they, unlike many other cells in the body, have very limited capacity to regenerate, thus permanently disrupting the body’s signal transmission and communication structure.

Senior author D. Kacy Cullen, PhD, an assistant professor of Neurosurgery and his team have been working to grow replacement connections, referred to as micro-tissue engineered neural networks (micro-TENNS), in the lab and test their ability to “wire-in” to replace broken axon pathways when implanted in the brain. Cullen’s team advanced the micro-TENNs to consist of discrete populations of mature cerebral cortical neurons spanned by long axonal projections within miniature hair-like structures. These micro-TENNs are the first transplantable neural networks that mimic the structure of brain pathways in a miniature form.

In a previous 2015 publication in Tissue Engineering, Cullen and colleagues showed that preformed micro- TENNS could be delivered into the brains of rats to form new brain architecture that simultaneously replaced neurons as well as long axonal projections. “The micro-TENNS formed synaptic connections to existing neural networks in the cerebral cortex and the thalamus – involved in sensory and motor processing – and maintained their axonal architecture for several weeks to structurally emulate long-distance axon connections,” Cullen reported. This work was the first to demonstrate that living micro-TENNS could successfully integrate into existing brain structures and reconstitute missing brain pathways, but, the team observed the need for improvement in how they were delivered to the brain, as this initial study required that the micro-TENNs be drawn into needles.