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Article

Three-Dimensional Regeneration of Patient-Derived Intestinal Organoid Epithelium in a Physiodynamic Mucosal Interface-on-a-Chip

1
Department of Biomedical Engineering, The University of Texas at Austin, Austin, TX 78712, USA
2
Department of Oncology, Dell Medical School, The University of Texas at Austin, Austin, TX 78712, USA
3
Department of Surgery and Perioperative Care, Dell Medical School, The University of Texas at Austin, Austin, TX 78712, USA
4
Severance Fecal Microbiota Transplantation Center, Severance Hospital, Department of Pediatrics, Yonsei University College of Medicine, Seoul 03722, Korea
5
Department of Computer Art, College of Art and Technology, Chung-Ang University, Seoul 06974, Korea
6
Department of Medical Engineering, College of Medicine, Yonsei University, Seoul 03722, Korea
*
Author to whom correspondence should be addressed.
These authors contributed equally to this work.
Micromachines 2020, 11(7), 663; https://doi.org/10.3390/mi11070663
Received: 1 May 2020 / Revised: 3 July 2020 / Accepted: 5 July 2020 / Published: 7 July 2020
The regeneration of the mucosal interface of the human intestine is critical in the host–gut microbiome crosstalk associated with gastrointestinal diseases. The biopsy-derived intestinal organoids provide genetic information of patients with physiological cytodifferentiation. However, the enclosed lumen and static culture condition substantially limit the utility of patient-derived organoids for microbiome-associated disease modeling. Here, we report a patient-specific three-dimensional (3D) physiodynamic mucosal interface-on-a-chip (PMI Chip) that provides a microphysiological intestinal milieu under defined biomechanics. The real-time imaging and computational simulation of the PMI Chip verified the recapitulation of non-linear luminal and microvascular flow that simulates the hydrodynamics in a living human gut. The multiaxial deformations in a convoluted microchannel not only induced dynamic cell strains but also enhanced particle mixing in the lumen microchannel. Under this physiodynamic condition, an organoid-derived epithelium obtained from the patients diagnosed with Crohn’s disease, ulcerative colitis, or colorectal cancer independently formed 3D epithelial layers with disease-specific differentiations. Moreover, co-culture with the human fecal microbiome in an anoxic–oxic interface resulted in the formation of stochastic microcolonies without a loss of epithelial barrier function. We envision that the patient-specific PMI Chip that conveys genetic, epigenetic, and environmental factors of individual patients will potentially demonstrate the pathophysiological dynamics and complex host–microbiome crosstalk to target a patient-specific disease modeling. View Full-Text
Keywords: gut-on-a-chip; organoid; mucosal interface; physiodynamic; multiaxial deformation; microbiome; co-culture; disease modeling gut-on-a-chip; organoid; mucosal interface; physiodynamic; multiaxial deformation; microbiome; co-culture; disease modeling
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MDPI and ACS Style

Shin, Y.C.; Shin, W.; Koh, D.; Wu, A.; Ambrosini, Y.M.; Min, S.; Eckhardt, S.G.; Fleming, R.Y.D.; Kim, S.; Park, S.; Koh, H.; Yoo, T.K.; Kim, H.J. Three-Dimensional Regeneration of Patient-Derived Intestinal Organoid Epithelium in a Physiodynamic Mucosal Interface-on-a-Chip. Micromachines 2020, 11, 663. https://doi.org/10.3390/mi11070663

AMA Style

Shin YC, Shin W, Koh D, Wu A, Ambrosini YM, Min S, Eckhardt SG, Fleming RYD, Kim S, Park S, Koh H, Yoo TK, Kim HJ. Three-Dimensional Regeneration of Patient-Derived Intestinal Organoid Epithelium in a Physiodynamic Mucosal Interface-on-a-Chip. Micromachines. 2020; 11(7):663. https://doi.org/10.3390/mi11070663

Chicago/Turabian Style

Shin, Yong C., Woojung Shin, Domin Koh, Alexander Wu, Yoko M. Ambrosini, Soyoun Min, S. G. Eckhardt, R. Y.D. Fleming, Seung Kim, Sowon Park, Hong Koh, Tae K. Yoo, and Hyun J. Kim. 2020. "Three-Dimensional Regeneration of Patient-Derived Intestinal Organoid Epithelium in a Physiodynamic Mucosal Interface-on-a-Chip" Micromachines 11, no. 7: 663. https://doi.org/10.3390/mi11070663

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