Integrating bioprinted oral epithelium with millifluidics for fluorouracil perfusion and Fusobacterium infection to bioengineer oral mucositis-on-a-chip

Oral mucositis (OM) remains a painful complication of anticancer chemotherapy (CT), tending to progress in severity in the presence of Fusobacterium nucleatum (Fn). Yet, no effective therapy exists to suppress OM since in vitro models mimicking CT-induced OM are lacking, halting the discovery of new drugs. Here, we developed an integrated millifluidic in vitro tissue culture system for OM disease modeling. This bioengineered system integrates magnetically bioassembled oral epithelium sheets with millifluidics for CT-based 5-fluorouracil perfusion and Fn infection to model CT-induced OM. After modeling OM with all pro-inflammatory hallmarks, we were able to suppress OM with our in-house plant-produced epidermal growth factor (P-EGF), a well-known re-epithelialization cue. Thus, this the first instance where a milifluidic system enabled OM modeling in the presence of CT drug perfusion and Fn infection. This bioengineered system is a novel tool for drug discovery as it propelled P-EGF as a promising therapy for OM.