01907nas a2200325   4500000000100000000000100001008004100002260001200043653001100055653003200066653001500098653001800113653001400131653001500145100002500160700001500185700001800200700002100218700001700239700001700256700002400273700002700297700002400324700002000348245008300368300001400451490000700465520109500472022001401567       2022                            d  c2022-1110aHumans10aInflammatory Bowel Diseases10aIntestines10aOrganogenesis10aorganoids10aStem cells1 aSunghee Estelle Park1 aShawn Kang1 aJungwook Paek1 aAndrei Georgescu1 aJeehan Chang1 aAlex Yoon Yi1 aBenjamin J. Wilkins1 aTatiana A. Karakasheva1 aKathryn E. Hamilton1 aDan Dongeun Huh00aGeometric engineering of organoid culture for enhanced organogenesis in a dish  a1449-14600 v193 aHere, we introduce a facile, scalable engineering approach to enable long-term development and maturation of organoids. We have redesigned the configuration of conventional organoid culture to develop a platform that converts single injections of stem cell suspensions to radial arrays of organoids that can be maintained for extended periods without the need for passaging. Using this system, we demonstrate accelerated production of intestinal organoids with significantly enhanced structural and functional maturity, and their continuous development for over 4 weeks. Furthermore, we present a patient-derived organoid model of inflammatory bowel disease (IBD) and its interrogation using single-cell RNA sequencing to demonstrate its ability to reproduce key pathological features of IBD. Finally, we describe the extension of our approach to engineer vascularized, perfusable human enteroids, which can be used to model innate immune responses in IBD. This work provides an immediately deployable platform technology toward engineering more realistic organ-like structures in a dish.  a1548-7105