Traumatic Nerve Injury Platform & Innervated Skin.

Program:

• Introduction to DuaLink Shift NeuroFluidics Devices & PNS NeuroFluidics Cultures

• Use Case #1 - Motor and Sensory Nerve Injury Platform: Regrowth after trauma

• Paves the way to study complex cell communication during regenerative processes by adding glial cells (e.g. satellite cells, Schwann cells) or target organs (e.g. skin, muscle) and to develop a electrophysiological digital signature of axonal regrowth

• Introduction of DuaLink MEA & Skin NeuroFluidics Cultures

• Use Case #2 - Innervated skin: compartmentalized co-culture of primary keratinocytes & hiPSC-derived sensory neurons

• Q&A

More details:

Traumatic Nerve Injury Platform

Accidents, surgeries, and compressions (tumor, carpal canal syndrome) are examples of situations in which a traumatic injury to the spinal cord or nerves can induce neuropathic pain in addition to debilitating motor and sensory symptoms. Two main axes of treatments have an important impact on a patient's quality of life: (i) regenerative medicine to reconstruct and regenerate nerves and (ii) efficient pain relief.

To offer a translational nerve injury platform enabling the discovery of regenerative therapeutics we used the DuaLink™ Delta Ultra from the Neurofluidics™ line. The microchannel length between channel 2 and 3 (Figure 2) allows the monitoring of neurite regrowth after injury in channel 2. The DuaLink™ Shift architecture offers the same advantages obtained from the microchannels’ length (500 µm) and compatibility with MEA readouts. As a mirror of current in vivo models, such as nerve crush injury or nerve ligation that aim to mimic human nerve trauma, we created a repeatable and standardized injury, by cutting motor and sensory axons only using a short, targeted detergent application. Our devices' microfluidic isolation and architecture offer the advantage of targeting only neurites and not cell bodies like conventional in vitro models. We demonstrated the use of our platform by comparing axonal regeneration following treatment with a neurotrophic molecule or with a drug inhibiting neurite outgrowth.

Innervated skin-on-chip

Topical drugs and cosmetic developments are limited by in-vitro models, which are not always relevant either because they use rodent cells, banned in the field of cosmetic, or because the cocultures of skin and neurons do not fully recapitulate the anatomical structure.

To address these limitations, we developed microfluidics devices using human cells (human iPSC-derived cells and primary cells) to reproduce i/ skin compartment with keratinocytes and nerve endings and ii/ spinal cord compartment with neuronal cell nucleus. We developed compartimentalized microfluidic devices allowing a fluidic isolation while allowing the physical connexion between neurons’ axons and skin cells.

Viability, maturation, and functionality have been successfully proved.

Speakers: Hélène Gautier | Alexandre Guichard