Fattahi, P. | Search bioRxiv

bioRxiv2026

Emulating the gingival-tooth interface during bacterial, fungal, and viral infection in a microphysiological model of the human oral cavity

The anatomical complexity and distinctive tissue environment of the human oral cavity pose major challenges to modeling oral infection and host-microbe interactions in preclinical laboratory settings. Here we present a bioengineered oral microphysiological system comprising vascularized human gingival tissue integrated with tooth analogs that together recreate a functional unit of the human oral cavity. We incorporated Streptococcus mutans and Candida albicans into this system to model cross-kingdom biofilm formation, microbial dissemination, and host-microbial interactions at the gingival-tooth interface. Single-cell RNA sequencing and global metabolomics analysis revealed that fungal colonization induces epithelial-to-mesenchymal transition associated with distinct transcriptional and metabolic signatures. Our platform also allowed us to simulate SARS-CoV-2 infection and examine gingival responses to live-virus challenge. Finally, we integrated the engineered gingival tissue with controlled human saliva flow to show that hyposalivation potentiates the pathogenic capacity of fungal infection. This work demonstrates the potential of oral microphysiological systems as an experimental platform for in vitro modeling and mechanistic investigation of host-microbe interactions under controlled, human-relevant conditions.

bioengineering↗

bioRxiv2024

A bioengineered model of human placental exposure to environmental metals during pregnancy

Exposure of pregnant women to toxic metals is an environmental health issue associated with various pregnancy complications. Efforts to advance our biological understanding of this problem and mitigate its adverse effects, however, have been challenged by ethical concerns of human subject research during pregnancy. Here, we present an alternative approach that leverages the design flexibility, controllability, and scalability of bioengineered human reproductive tissues to enable experimental simulation and in-depth investigation of placental exposure to environmental metals in maternal circulation. Central to this method is an in vitro analog of the maternal-fetal interface and its dynamic tissue-specific environment constructed using primary human placental cells grown in a micro-engineered device. Using cadmium as a representative toxicant, we demonstrate the proof-of-concept of emulating the human placental barrier subjected to the flow of cadmium-containing maternal blood to show how this model can be used to examine adverse biological responses and impaired tissue function on both the maternal and fetal sides. Moreover, we present a mechanistic study of maternal-to-fetal cadmium transport in this system to reveal that efflux membrane transporters expressed by trophoblasts may play an important protective role against cadmium-induced toxicity. Finally, we describe metabolomic analysis of our microphysiological system to demonstrate the feasibility of discovering metabolic biomarkers that may potentially be useful for detection and monitoring of cadmium-induced placental dysfunction.

bioengineering↗