Oral mucositis on a chip: modeling induction by chemo- and radiation treatments and recovery

Abstract

Oral mucositis (OM) is a debilitating complication affecting roughly 70% of head and neck cancer patients receiving chemotherapy and/or radiation treatment. No broadly effective preventative treatment for OM exists. Therefore, an in vitro model of cancer treatment-induced OM would aid studies into possible origins of the pathology and future drug targets to ameliorate it. In this study, we present a microfluidic oral mucosa triculture tissue construct consisting of a keratinocyte layer attached to a subepithelial fibroblast and endothelial cell-embedded collagen gel. To address the typically low stability of mucosal constructs in microfluidics, ruthenium-catalyzed photocrosslinking was implemented to strengthen the collagen gel and prevent the invasion of keratinocytes, thus maintaining tissue construct geometry and oral mucosa barrier function for over 18 d of culture. Next, the OM chip was exposed to cisplatin (day 10) and damaging radiation (day 11, ± cisplatin at day 10), mimicking damage from cancer therapy. Damage to and then recovery of the tissue layers and function were observed over days 11–18. Therefore, several important features of OM induction and resolution were modeled in microfluidic culture. The OM model on a chip allows for more sophisticated studies into mechanisms of OM and potential treatments.