Abstract
AbstractOrgan on chip (OoC) technologies have the potential to improve the translation of promising therapies currently failing in clinical trials at great expense and time due to dissimilarities between animal and human biology. Successful OoC models integrate human cells within 3D tissues with surrounding biomolecular components, and have benefited from the use of inert 3D gels and scaffolds used as templates, prompting tissue formation. However, monitoring technologies used to assess tissue integrity and drug effects are ill adapted to 3D biology. Here, a tubular electroactive scaffold serves as a template for a 3D human intestine, and enables dynamic electrical monitoring of tissue formation over 1 month. Cell‐ and extracellular matrix component‐invoked changes in the properties of the scaffold alleviate the need for posthoc placement of invasive metallic electrodes or downstream analyses. Formation of in vivo‐like stratified and polarized intestinal tissue compete with lumen contrasts with other quasi‐3D models of the intestine using rigid porous membrane to separate cell types. These results provide unprecedented real‐time information on tissue formation with highly sensitive multimodal operation, thanks to dual electrode and transistor operation. This device and the methodology for tissue growth within it represents a paradigm shift for disease modeling and drug discovery.
Highlights
Until recently, such efforts have been limited to 2D models, which rely on culturing established human intestinal cell lines within Transwell insert culture metallic electrodes or downstream analyses
We observed a significant increase of the overall magnitude of the impedance during the proliferation of intestinal cells and the maturation of the epithelial barrier
This work represents the first instance of a 3D human intestinal tissue with seamlessly integrated sensing components incorporated into the heart of the tissue, that allow for continuous monitoring of cell status and activity for 1 month
Summary
We used a co-culture of intestinal epithelial cells (IECs) comprising Caco-2 cells and HT29-MTX cells (in a 3:1 ratio to mimic in vivo conditions), commonly found in in vitro models of the intestinal barrier.[17,45,46] Both cell lines are derived from human adenocarcinoma, in culture they spontaneously differentiate toward mature enterocyte-like (Caco-2) and goblet-like cells (HT29-MTX) forming functional intestinal epithelial layers with a typical apical brush border and tight junctions. As demonstrated by ECM protein staining (Figure S3, Supporting Information), scaffolds were fully infiltrated by TIFs and an extensive ECM protein network This might affect the size and properties of the porous electrode, explaining the dramatic decrease in impedance magnitude observed. A peak ΔR/Ro was observed after 2 weeks of IEC culture while ΔC/Co revealed a gradual decrease (with an acute initial drop) over time This behavior is likely attributable to the decrease of the available surface area ( the volumetric capacitance of the scaffold) due to the presence of cells at the luminal interface and the formation of tight junctions at this stage of tissue development. A substantial initial drop in the relative gm over time is observed, to Figure 4D, attributed to the initial phase of cell growth, consistent with previous observations.[44]
Sign-in/Register to view highlights & summary Sign-in/Register to access full text options 
Talk to us
Join us for a 30 min session where you can share your feedback and ask us any queries you have
Schedule a callDisclaimer: All third-party content on this website/platform is and will remain the property of their respective owners and is provided on "as is" basis without any warranties, express or implied. Use of third-party content does not indicate any affiliation, sponsorship with or endorsement by them. Any references to third-party content is to identify the corresponding services and shall be considered fair use under The CopyrightLaw.
