Rebuilding brain circuitry with living micro-tissue engineered neural networks

It mentions long distance axonal connections. This is something I could have greatly used since I assume that a huge chunk of my white matter underlying my dead premotor and motor cortex also is dead and there is miles of neuronal connections I need to replace. If we had anything even close to an objective damage diagnosis my doctors would know exactly what was damaged and how to initiate fixes to those problems. But that won't occur until we get rid of the deadwood in the current stroke leadership.
http://online.liebertpub.com/doi/abs/10.1089/ten.TEA.2014.0557?journalCode=tea

To cite this article:
Miss Laura A. Struzyna, Dr. John A. Wolf, Miss Constance J. Mietus, Mr. Dayo Olaolu Adewole, Dr. H. Isaac Chen, Dr. Douglas Smith, and Dr. D. Kacy Cullen. Tissue Engineering Part A. -Not available-, ahead of print. doi:10.1089/ten.TEA.2014.0557.

Online Ahead of Editing: September 28, 2015

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Author information

Miss Laura A. Struzyna

University of Pennsylvania, Bioengineering, Philadelphia, Pennsylvania, United States

;

University of Pennsylvania, Neurosurgery, Philadelphia, Pennsylvania, United States

;

Philadelphia Veterans Affairs Medical Center, Phladelphia, Pennsylvania, United States; lstruz@mail.med.upenn.edu

Dr. John A. Wolf

University of Pennsylvania, Neurosurgery, Philadelphia, Pennsylvania, United States

;

Philadelphia Veterans Affairs Medical Center, Philadelphia, Pennsylvania, United States; wolfjo@upenn.edu

Miss Constance J. Mietus

University of Pennsylvania, Neurosurgery, Philadelphia, Pennsylvania, United States; mietusc@gmail.com

Mr. Dayo Olaolu Adewole

University of Pennsylvania, Bioengineering, Philadelphia, Pennsylvania, United States

;

University of Pennsylvania, Neurosurgery, Philadelphia, Pennsylvania, United States

;

Philadelphia Veterans Affairs Medical Center, Phladelphia, Pennsylvania, United States; oadewole@seas.upenn.edu

Dr. H. Isaac Chen

University of Pennsylvania, Neurosurgery, Philadelphia, Pennsylvania, United States

;

Philadelphia Veterans Affairs Medical Center, Phladelphia, Pennsylvania, United States; isaac.chen@uphs.upenn.edu

Dr. Douglas Smith

University of Pennsylvania, Neurosurgery, Philadelphia, Pennsylvania, United States; smithdou@mail.med.upenn.edu

Dr. D. Kacy Cullen, PhD

University of Pennsylvania, Neurosurgery, Philadelphia, Pennsylvania, United States

;

Philadelphia Veterans Affairs Medical Center, Phladelphia, Pennsylvania, United States; dkacy@mail.med.upenn.edu

Accepted: 09 22 2014
Received: 09 22 2014

ABSTRACT

Prominent neuropathology following trauma, stroke and various neurodegenerative diseases includes neuronal degeneration as well as loss of long-distance axonal connections. While cell replacement and axonal pathfinding strategies are often explored independently, there is no strategy capable of simultaneously replacing lost neurons and re-establishing long-distance axonal connections in the central nervous system. Accordingly, we have created micro-tissue engineered neural networks (micro-TENNs) which are preformed constructs consisting of long integrated axonal tracts spanning discrete neuronal populations. These living micro-TENNs reconstitute the architecture of long-distance axonal tracts, and thus may serve as an effective substrate for targeted neurosurgical reconstruction of damaged pathways in the brain. Cerebral cortical neurons or dorsal root ganglia neurons were precisely delivered into the tubular constructs, and properties of the hydrogel exterior and extracellular matrix internal column (250 - 500 μm diameter) were optimized for robust neuronal survival and to promote axonal extensions across the 2.0 cm tube length. The very small diameter permits minimally invasive delivery into the brain. Here, pre-formed micro-TENNs were stereotaxically injected into naïve rats to bridge deep thalamic structures with the cerebral cortex in order to assess construct survival and integration. We found that micro-TENN neurons survived at least one month and maintained their long axonal architecture along the cortical-thalamic axis. Notably, we also found neurite penetration from micro-TENN neurons into the host cortex, with evidence of synapse formation. These micro-TENNs represent a new strategy to facilitate nervous system repair by recapitulating features of neural pathways to restore or modulate damaged brain circuitry.