Dr. Kacy Cullen, University of Pennsylvania

Cullen and his colleagues are in hot pursuit of “neurosurgical reconstruction.” The idea is to rebuild brain circuitry with what they call “living electrodes”: tiny, biodegradable tubes packed with axons, the long filaments that carry signals out of one neuron and into another. The tubes are inserted into a brain, they melt away, and the axons form functional circuits with the rest of the cortex. It’s already worked in rat brains, the scientists reported in November, so 2016 could bring more progress toward rebuilding brains damaged by trauma and degenerative diseases such as Parkinson’s.

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Find the pdf here: http://online.liebertpub.com/doi/full/10.1089/ten.tea.2014.0557

Struzyna Laura A., et al. 2015

Tissue Engineering Part A.  21(21-22): 2744-2756. doi:10.1089/ten.tea.2014.0557.

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 (180–500 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. In this study, preformed micro-TENNs were stereotaxically injected into naive rats to bridge deep thalamic structures with the cerebral cortex to assess construct survival and integration. We found that micro-TENN neurons survived at least 1 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.

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