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They remain static due to the absence of peristalsis movements, lack important cell types like blood vessel-forming endothelial cells and immune cells, and do not have a normal intestine lumen that experiences fluid flow and is easily accessible to analysis. As a result, many studies involving, for example, drug and nutrient transport, or the interaction between the intestine and living commensal microbial communities cannot be performed in the experimental models.

These challenges have recently been overcome using microfluidic Organ-on-a-Chip Organ Chip technology. The Intestine Chip models contain mechanically active, continuously perfused microchannels inhabited by different human intestinal cell populations that form tissues with in vivo -like morphologies, which can be functionally interfaced with each other, the living intestinal microbiome and immune system.

The human intestinal epithelium with its villi-like structure and human vascular endothelium are lined on opposite sides of a flexible membrane under flow and peristalsis-like motions purple arrows. This engineered intestinal microenvironment undergoes complex interactions indicated by the blue arrows in the zoom-in schematic on the bottom with commensal gut microbiome, bacterial pathogens, and immune cells.

Credit: Wyss Institute at Harvard University Modeling physiological and pathophysiological processes in the human intestinal tract outside the human body has been a daunting challenge for bioengineers. Lab Chip 15, — Abbott, A. Biology' s new dimension.

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Nature , — Ahadian, S. Organ-on-a-chip platforms: a convergence of advanced materials, cells, and microscale technologies. Alberti, M. Multi-chamber microfluidic platform for high-precision skin permeation testing.

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Lab Chip 17, — Bae, S. Battiston, K. Biomaterials in co-culture systems: towards optimizing tissue integration and cell signaling within scaffolds. Biomaterials 35, — Benam, K. Small airway-on-a-chip enables analysis of human lung inflammation and drug responses in vitro. Methods 13, — Beyer, I. Overcoming physical barriers in cancer therapy. Tissue Barriers. Bhatia, S. Microfluidic organs-on-chips.

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Bollenbach, T. Gradients are shaping up. Cell , — Cerchiari, A. Formation of spatially and geometrically controlled three-dimensional tissues in soft gels by sacrificial micromolding. Tissue Eng. Part C Methods 21, — Chang, C. Direct-write bioprinting three-dimensional biohybrid systems for future regenerative therapies. B 98, — Choe, A. Microfluidic Gut-liver chip for reproducing the first pass metabolism. Cimetta, E. Lab Chip 10, — Cirit, M.

Maximizing the impact of microphysiological systems with: in vitro - In vivo translation. Lab Chip 18, — Costello, C. Microscale Bioreactors for in situ characterization of GI epithelial cell physiology. Crosnier, C. Organizing cell renewal in the intestine: stem cells, signals and combinatorial control.

Dekkers, J. A functional CFTR assay using primary cystic fibrosis intestinal organoids. Derby, B. Printing and prototyping of tissues and scaffolds. Science Fang, Y.


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Three-dimensional cell cultures in drug discovery and development. SLAS Discov. Fitzpatrick, L. Cell-derived matrices for tissue engineering and regenerative medicine applications. Thesis, Universitat de Barcelona. Gayer, C. The effects of mechanical forces on intestinal physiology and pathology. Cell Signal. Gopinathan, J.

Recent trends in bioinks for 3D printing. Griffith, L. Capturing complex 3D tissue physiology in vitro. Cell Biol. Hassell, B. Human organ chip models recapitulate orthotopic lung cancer growth, therapeutic responses, and tumor dormancy in vitro human organ chip models recapitulate orthotopic lung cancer growth, therapeutic responses, and tumor dormancy in vitro. Cell Rep.

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He, P. Bioprinting of skin constructs for wound healing. Trauma 6, 5. Henry, O. Homan, K. Bioprinting of 3D Convoluted renal proximal tubules on perfusable chips. Huh, D. Reconstituting organ-level lung functions on a chip. Science , — doi: Ishiguro, T. Tumor-derived spheroids: relevance to cancer stem cells and clinical applications. Cancer Sci. Kasendra, M. Development of a primary human Small Intestine-on-a-Chip using biopsy-derived organoids. Kim, H. Human gut-on-a-chip inhabited by microbial flora that experiences intestinal peristalsis-like motions and flow.

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Lab Chip 12, — Gut-on-a-Chip microenvironment induces human intestinal cells to undergovillus differentiation. Contributions of microbiome and mechanical deformation to intestinal bacterial overgrowth and inflammation in a human gut-on-a-chip. Kirkpatrick, C.

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