This study presents a 3D in vitro rat nerve-on-a-chip (RNoaC) model designed to evaluate nerve function and pathology in chemotherapy-induced peripheral neuropathy (CIPN). By culturing embryonic rat dorsal root ganglia within a dual hydrogel construct, the platform enables clinically relevant electrophysiological measurements and histological analysis. Exposure to chemotherapeutics including paclitaxel, bortezomib, oxaliplatin, and vincristine led to concentration-dependent declines in nerve conduction velocity (NCV) and peak amplitude (AMP), with detectable dysfunction preceding decreases in cell viability. This suggests the model’s strong potential for early neurotoxicity screening.
Researchers fabricated a dual hydrogel construct on Transwell® inserts using photolithography. Embryonic rat dorsal root ganglia (DRGs) were embedded into the construct and cultured through pre-myelination and myelination phases. After 4 weeks, constructs were exposed to chemotherapeutic agents. NCV and AMP were recorded using electrophysiological setups mimicking clinical practices. Additional assays included histology, immunocytochemistry, mitochondrial membrane potential staining (TMRE), and viability tests (CCK-8 and LDH).
The RNoaC model successfully mimics features of CIPN and provides a physiologically relevant, cost-effective platform for preclinical screening. By capturing early functional impairments and corresponding histopathological changes, this model represents a significant advancement in in vitro neurotoxicity testing and has the potential to reduce reliance on animal models in drug development.
Kramer L, Nguyen HT, Jacobs E, McCoy L, Curley JL, Sharma AD, Moore MJ. Modeling chemotherapy-induced peripheral neuropathy using a nerve-on-a-chip microphysiological system. ALTEX. 2020;37(3):350-364. doi:10.14573/altex.2001181
