Microphysiological Modeling of Gingival Tissues and Host-Material Interactions Using Gingiva-on-Chip.

Gingiva plays a crucial barrier role at the interface of teeth, tooth-supporting structures, microbiome, and external agents. To mimic this complex microenvironment, we developed an in vitro microphysiological platform and biofabricated full-thickness gingival equivalents (gingiva-on-chip) within a vertically-stacked microfluidic device. This design allowed long-term and air-liquid interface culture, and host-material interactions under flow conditions. Compared to static cultures, dynamic cultures on-chip enabled the biofabrication of gingival equivalents with stable mucosal matrix, improved epithelial morphogenesis, and barrier features. Additionally, a diseased state with disrupted barrier function representative of gingival/oral mucosal ulcers was modeled. The apical flow feature was utilized to emulate the mechanical action of mouth rinse and integrate the assessment of host-material interactions and transmucosal permeation of oral-care formulations in both health and diseased states. Although the gingiva-on-chip cultures had thicker and more mature epithelium, the flow of oral-care formulations induced increased tissue disruption and cytotoxic features compared to static conditions. The realistic emulation of mouth rinsing action facilitated a more physiological assessment of mucosal irritation potential. Overall, this microphysiological system enables biofabrication of human gingiva equivalents in intact and ulcerated states, providing a miniaturized and integrated platform for downstream host-material and host-microbiome applications in gingival and oral mucosa research. This article is protected by copyright. All rights reserved.