Researchers See Hope for Brain-Connection Repair

PHILADELPHIA (CN) - Lab-grown neural networks can replace brain connections damaged by injury or disease and can be delivered with minimal disruption to tissue, according to new research published in the Journal of Neural Engineering.

Long-distance signal transmitting structures connecting clusters of neurons in the brain have a limited capacity to regenerate when damaged, thus disrupting the body's communication structure, according to an announcement by the University of Pennsylvania, Perelman School of Medicine.

Senior author of the new study, D. Kacy Cullen, PhD, an assistant professor of Neurosurgery and his team have been working to grow replacement connections in the lab that replace the broken pathways when implanted in the brain, according to the school.

Cullen's team advanced the micro-TENNs, which stands for "micro-tissue engineered neural networks." The advance consists of clusters of mature cerebral cortical neurons spanned by lengths of signal-transmitting connections within miniature hair-like structures.

These micro-TENNs, initially developed in collaboration with Doug Smith, MD, Robert A. Groff Professor of Teaching and Research in Neurosurgery and director of Penn's Center for Brain Injury and Repair, are the first transplantable neural networks that mimic the structure of brain pathways in a miniature form, the school reported.

In a 2015 publication in the journal 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 and the connections, called "axons."

"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 of the rat study.

This work was the first to demonstrate that living micro-TENNs could successfully integrate into existing brain structures and reconstitute missing brain pathways, but, improvement was needed in the delivery process, which required drawing the structures into needles, the school reported.

In response, the research team developed a new, less invasive delivery method by applying an ultra-thin coating to the micro-TENNs using a gel commonly found in food and biomedical products. This new strategy allows insertion without a needle.

"We searched for materials that could form a hard shell that would soften immediately following insertion to better match the mechanical properties of the native brain tissue," Cullen was quoted as saying in the announcement.

This, the team hypothesized, would minimize the body's reaction and improve the survival and integration of the neural networks, the school reported.

The needleless method substantially reduces the implant footprint, suggesting that it would cause less damage and thus provide a more hospitable environment for implanted neurons to integrate with the brain's existing nervous system, the announcement stated.

"Additional research is required to directly test micro-TENN neuron survival and integration for each of these insertion methods," Cullen said.

"We hope this regenerative medicine strategy will someday enable us to grow individualized neural networks that are tailored for each patient's specific need," he added, "ultimately to replace lost neural circuits and improve brain function."

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