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Nerve guidance device for the treatment of CNS disease and injury

A damaging or pathological process that disrupts the continuity of axons in the adult mammalian central nervous system (CNS) often results in permanent disability due to the failure of injured axons to regenerate. Current therapeutic interventions are short of eliciting a robust regenerative response that leads to a decent degree of functional recovery. Recently, the emergence of neural bridging devices based upon tissue engineering principles offers new hope for the treatment and manipulation of CNS injuries and diseases. By engineering a controlled environment at the lesion site, neural bridging devices awaken the intrinsic ability of CNS axons to regenerate across and beyond the site of injury to reach their appropriate targets. The combined use of material scaffolds containing guidance cues with grafted cells of selective properties further confers vitality and resilience to the devices. Our long-term goal is to develop a clinically applicable tissue-engineered neuronal bridging device to repair damaged CNS nerve tracts.
It is generally believed that organized neural architecture is essential for both CNS development and function. During development, proliferation of new neurons occurs only after formation of the neural tube. Migration of new neurons along a fan-like scaffold of aligned radial glial threads gives rise to the neocortex. Also, fascicles of axons grow along the routes established by pioneer axons that outline permissive paths for them to reach their targets. Such organized architecture is important for signal transduction, axonal pathfinding, and synaptic formation. Disruption of cellular, molecular, and anatomical organizations of the normal CNS may lead to partial or complete neurological disorders. In support of this notion, we have designed and constructed a tissue-engineered neural bridging device (Figure below) to mimic the normal architecture and guide axonal regeneration within the damaged CNS. This is done by entubulating ultrathin filament bundles seeded with cells of selective properties into a semi-permeable hollow fiber membrane (HFM).
We are focusing on three aspects to further promote spinal cord regeneration following injury: 1) Developing therapeutic agent-releasing guidance device. For example, device loaded with 4-nitrophenyl- -D-xylopyranoside (PNPX), EGFR inhibitor, neuroprotective agents, inflammation suppressing agents (such as anti-inflammatory cytokines: IL-10 and IL-4), and scar depleting agents. 2) Incorporating customized stem cells into the device to help recovering from functional cell loss due to the injury or suppressing glial scar formation; and 3) Identifying an optimal combination of physical, chemical, and biological guidance cues of the bridging device and applying the optimal device into clinically relevant applications to benefit patients with spinal cord injury.