Establishment of physiologically relevant oxygen gradients in microfluidic organ chips.

Autor:	Grant J; Wyss Institute for Biologically Inspired Engineering, Harvard University, Boston, MA 02115, USA. don.ingber@wyss.harvard.edu., Lee E; Wyss Institute for Biologically Inspired Engineering, Harvard University, Boston, MA 02115, USA. don.ingber@wyss.harvard.edu., Almeida M; Wyss Institute for Biologically Inspired Engineering, Harvard University, Boston, MA 02115, USA. don.ingber@wyss.harvard.edu., Kim S; Wyss Institute for Biologically Inspired Engineering, Harvard University, Boston, MA 02115, USA. don.ingber@wyss.harvard.edu., LoGrande N; Wyss Institute for Biologically Inspired Engineering, Harvard University, Boston, MA 02115, USA. don.ingber@wyss.harvard.edu., Goyal G; Wyss Institute for Biologically Inspired Engineering, Harvard University, Boston, MA 02115, USA. don.ingber@wyss.harvard.edu., Sesay AM; Wyss Institute for Biologically Inspired Engineering, Harvard University, Boston, MA 02115, USA. don.ingber@wyss.harvard.edu., Breault DT; Division of Endocrinology, Boston Children's Hospital, Boston, MA 02115, USA.; Department of Pediatrics, Harvard Medical School, Boston, MA, 02115, USA.; Harvard Stem Cell Institute, Harvard University, Boston, MA 02139, USA., Prantil-Baun R; Wyss Institute for Biologically Inspired Engineering, Harvard University, Boston, MA 02115, USA. don.ingber@wyss.harvard.edu., Ingber DE; Wyss Institute for Biologically Inspired Engineering, Harvard University, Boston, MA 02115, USA. don.ingber@wyss.harvard.edu.; Harvard John A. Paulson School of Engineering and Applied Sciences, Harvard University, Cambridge, MA 02138, USA.; Vascular Biology Program and Department of Surgery, Harvard Medical School and Boston Children's Hospital, Boston, MA 02115, USA.
Jazyk:	angličtina
Zdroj:	Lab on a chip [Lab Chip] 2022 Apr 12; Vol. 22 (8), pp. 1584-1593. Date of Electronic Publication: 2022 Apr 12.
DOI:	10.1039/d2lc00069e
Abstrakt:	In vitro models of human organs must accurately reconstitute oxygen concentrations and gradients that are observed in vivo to mimic gene expression, metabolism, and host-microbiome interactions. Here we describe a simple strategy to achieve physiologically relevant oxygen tension in a two-channel human small intestine-on-a-chip (Intestine Chip) lined with primary human duodenal epithelium and intestinal microvascular endothelium in parallel channels separated by a porous membrane while both channels are perfused with oxygenated medium. This strategy was developed using computer simulations that predicted lowering the oxygen permeability of poly-dimethylsiloxane (PDMS) chips in specified locations using a gas impermeable film will allow the cells to naturally decrease the oxygen concentration through aerobic respiration and reach steady-state oxygen levels <36 mm Hg (<5%) within the epithelial lumen. The approach was experimentally confirmed using chips with embedded oxygen sensors that maintained this stable oxygen gradient. Furthermore, Intestine Chips cultured with this approach supported formation of a villus epithelium interfaced with a continuous endothelium and maintained intestinal barrier integrity for 72 h. This strategy recapitulates in vivo functionality in an efficient, inexpensive, and scalable format that improves the robustness and translatability of Organ Chip technology for studies on microbiome as well as oxygen sensitivity.
Databáze:	MEDLINE
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