Modeling chemotherapy-induced peripheral neuropathy using a Nerve-on-a-chip microphysiological system.

Area of Science:

• Biomedical Engineering
• Neuroscience
• Toxicology

Background:

• Organ-on-a-chip technology offers a promising alternative to animal models for preclinical drug testing.
• Chemotherapy-induced peripheral neuropathy (CIPN) is a significant clinical challenge with limited in vitro models for study.
• Existing in vitro models often lack the physiological complexity to accurately predict in vivo nerve responses.

Purpose of the Study:

• To develop and validate a 3D hydrogel rat nerve-on-a-chip (RNoaC) construct for studying peripheral neuropathy.
• To assess the RNoaC's capability in detecting functional and structural nerve damage caused by chemotherapeutic agents.
• To establish RNoaC as a preclinical assay for screening CIPN implications.

Main Methods:

• Cultured embryonic rat dorsal root ganglia (DRG) within a hydrogel RNoaC construct.
• Exposed DRG explants to common chemotherapeutics (bortezomib, oxaliplatin, paclitaxel, vincristine).
• Collected electrophysiological data (nerve conduction velocity, peak amplitude) and performed histopathological analysis after 7 days.

Main Results:

• All tested chemotherapeutics caused a dose-dependent decrease in nerve conduction velocity and peak amplitude.
• Electrophysiological changes indicated significant nerve dysfunction preceding loss of cell viability.
• Histopathological analysis confirmed hallmarks of peripheral neuropathy within the RNoaC model.

Conclusions:

• The RNoaC platform successfully mimics key aspects of in vivo nerve pathophysiology.
• Electrophysiology recordings from RNoaC closely track subtle pathological changes in nerve function.
• RNoaC serves as an effective in vitro tool for preclinical screening of peripheral neuropathy and drug-induced nerve damage.