Exposure to toxins or gut dysbiosis (microbial imbalance) is known to influence the physiological function of the gut endothelium and is involved in several intestinal diseases and even mental disorders. The disruption of gut bacteria often damages cell integrity leading to increased permeability and susceptibility to chronic disease. Current in vivo models lack the ability to interrogate and modulate biological signaling at cellular length scales and in real time. With their ability to co-host multiple human cell types and gut microbiota, synthetic in vitro models such as Organ-on-a-chip (OOC) offer the potential to precisely control microenvironments for better understanding gut physiology. Oftentimes, however, in vitro OOC’s rely on cell self-assembly to fully reconstruct critical features of intestinal villi, such as their 3D structure and the embedded the capillary system. It is believed that these features play a significant role, however, in determining cell-cell interaction. For example, the oxygen tension and redox environment extending from the crypts to the villus tips vary tremendously. To gain insight, we have developed a 3D-printed, microbial flora co-cultured human villi-on-a-chip model with an internal capillary system for real-time monitoring of cellular permeability and redox signaling. Our capillary system recapitulates apical and basal transport in a structurally relevant model. The villus scaffold is assembled with ultra-high spatial resolution (less than 1 mm) owing to a new two-photon 3D printing system. The reduced size has also allowed for more rapid and physiologically relevant mass transport by reducing the overall volume. This ensures that our embedded sensor methodology pairs physiological responses to programmed metabolic inputs. In addition, because we employ a modular sensor configuration, cytotoxicity is rapidly quantified via exogenous substrates and an LDH activity assay. Together, by advancing 3D printing configurations that faithfully recapitulate the geometric landscape and at the same time enable molecular interrogation of the signaling events, we are in a position to discover new insight on the GI tract, the progression towards disease, as well as the potential for new therapies.

3D-printed human villi-on-a-chip with capillary system for drug screening and disease interrogation

2019 Spring National Meeting

The official archive and repository for all ACS Meetings & Expositions abstracts and select posters or presentations.