To combat high drug development costs, long preclinical testing timelines, and high clinical testing failure rates, AxoSim Technologies has developed Nerve-on-a-Chip, a platform that uses living human cells in a 3D, in vitro environment to grow and model human nerve tissue.
The technology was spun out of the lab of Dr. Michael Moore, Ph.D. at Tulane University’s Department of Biomedical Engineering where Dr. Lowry Curley, AxoSim’s CEO, completed his Ph.D. in 2012. Together, Curley and Moore, AxoSim’s Chief Science Officer, founded AxoSim. Along with a team of five other engineers, scientists, and entrepreneurs, they have continued to develop their technology and market it to pharmaceutical companies as a service provider.
Organ-on-a-chip or organoid-on-a-chip technologies are 3D culture systems designed to study physiology and disease using a biomimetic tissue model. Research into these technologies began in the late 1990s and has since expanded to include models of the liver, lung, intestine, heart, kidney, cornea, and some cancers.
Capturing physical tissue characteristics in 3D cultures seems to be key to modeling complex tissue function, including cell signaling networks. As models continue to improve and capture more clinically relevant biological markers and functional aspects of organ physiology, they may become central to drug toxicity screening and preclinical tests . Organotypic nerve tissue models will need to yield physiological measures that mimic clinical measures of nerve function, which include compound action potentials (CAP) and nerve fiber density (NFD) tests .
AxoSim’s Nerve-on-a-Chip technology enables the growth of a dense, highly parallel neural fiber tract that can be used to perform clinically relevant tests including the measurement of CAP and NFD. Early experiments with this system used explants from rat embryonic dorsal root ganglion (DRG) tissue to create functional models of peripheral nervous tissue. Narrow tracts approximately 490 μm across and 3 mm long filled with Puramatrix, a synthetic peptide hydrogel, allowed neurite growth extending from the ganglion, while polyethylene glycol (PEG) regions inhibited growth to the desired 3D geometry. The research team then tested the functional properties of the 3D culture conducting intracellular and extracellular electrophysiological recordings.
For extracellular experiments, a recording electrode was placed near the ganglion with a stimulating electrode inserted along the neurite tract. Stimulation of the tract produced a compound action potential whose conduction amplitude and delay were related to the stimulation location. Stimulation further from the ganglion resulted in an increased delay and decreased mean response amplitude as compared to stimulation closer to the ganglion. Their results closely mimicked the characteristics of afferent sensory peripheral fibers found in vivo .
AxoSim has developed models for preclinical assays to predict neurotoxicity, and disease models for neurodegenerative diseases including multiple sclerosis and amyotrophic lateral sclerosis. AxoSim was recently awarded a $1.7M Phase II SBIR grant from NIH to continue to develop its neurotoxicity testing capabilities.
- Astashkina, A. & Grainger, D. W. Critical analysis of 3-D organoid in vitro cell culture models for high-throughput drug candidate toxicity assessments. Adv. Drug Deliv. Rev. (2014). http://linkinghub.elsevier.com/retrieve/pii/S0169409X14000301
- Huval, R. M. et al. Microengineered peripheral nerve-on-a-chip for preclinical physiological testing. Lab Chip (2015). http://xlink.rsc.org/?DOI=C4LC01513D
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Image Credit: AxoSim