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Here, 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.

Here we present a miniaturized analog of a blinking human eye to reverse engineer the complexity of the interface between the ocular system and the external environment. Our model comprises human cells and provides unique capabilities to replicate multiscale structural organization, biological phenotypes and dynamically regulated environmental homeostasis of the human ocular surface. Using this biomimetic system, we discovered new biological effects of blink-induced mechanical forces. Furthermore, we developed a specialized in vitro model of evaporative dry-eye disease for high-content drug screening. This work advances our ability to emulate how human physiological systems interface with the external world, and may contribute to the future development of novel screening platforms for biopharmaceutical and environmental applications. A biomimetic culture system is developed by reverse engineering to replicate key features of the human ocular surface at cellular, tissue and organ levels, and is used as an in vitro model of dry-eye disease compatible with drug-screening approaches.

Diverse biological processes in the body rely on the ability of cells to exert contractile forces on their extracellular matrix (ECM). In three-dimensional (3D) cell culture, however, this intrinsic cellular property can cause unregulated contraction of ECM hydrogel scaffolds, leading to a loss of surface anchorage and the resultant structural failure of in vitro tissue constructs. Despite advances in the 3D culture technology, this issue remains a significant challenge in the development and long-term maintenance of physiological 3D in vitro models. Here, we present a simple yet highly effective and accessible solution to this problem. We leveraged a single-step surface functionalization technique based on polydopamine to drastically increase the strength of adhesion between hydrogel scaffolds and cell culture substrates. Our method is compatible with different types of ECM and polymeric surfaces and also permits prolonged shelf storage of functionalized culture substrates. The proof-of-principle of this technique was demonstrated by the stable long-term (1 month) 3D culture of human lung fibroblasts. Furthermore, we showed the robustness and advanced application of the method by constructing a dynamic cell stretching system and performing over 100 000 cycles of mechanical loading on 3D multicellular constructs for visualization and quantitative analysis of stretch-induced tissue alignment. Finally, we demonstrated the potential of our technique for the development of microphysiological in vitro models by establishing microfluidic 3D co-culture of vascular endothelial cells and fibroblasts to engineer self-assembled, perfusable 3D microvascular beds.

Century-old Langmuir monolayer deposition still represents the most convenient approach to the production of monolayers of colloidal nanoparticles on solid substrates for practical biological and chemical-sensing applications. However, this approach simply yields arbitrarily shaped large monolayers on a flat surface and is strongly limited by substrate topography and interfacial energy. Here, we describe a generalized and facile method of rapidly producing uniform monolayers of various colloidal nanoparticles on arbitrary solid substrates by using an ordinary capillary tube. Our method is based on an interesting finding of inversion phenomenon of a nanoparticle-laden air–water interface by flowing through a capillary tube in a manner that prevents the particles from adhesion to the capillary sidewall, thereby presenting the nanoparticles face-first at the tube’s opposite end for direct and one-step deposition onto a substrate. We show that our method not only allows the placement of a nanoparticle monolayer at target locations of solid substrates regardless of their surface geometry and adhesion but also enables the production of monolayers containing nanoparticles with different size, shape, surface charge, and composition. To explore the potential of our approach, we demonstrate the facile integration of gold nanoparticle monolayers into microfluidic devices for the real-time monitoring of molecular Raman signals under dynamic flow conditions. Moreover, we successfully extend the use of our method to developing on-demand Raman sensors that can be built directly on the surface of consumer products for practical chemical sensing and fingerprinting. Specifically, we achieve both the pinpoint deposition of gold nanoparticle monolayers and sensitive molecular detection from the deposited region on clothing fabric for the detection of illegal drug substances, a single grain of rice and an orange for pesticide monitoring, and a $100 bill as a potential anti-counterfeit measure, respectively. We believe that our method will provide unique opportunities to expand the utility of colloidal nanoparticles and to greatly improve the accessibility of nanoparticle-based sensing technologies.

Our 10-day diary investigation anchored in dynamic personality theories, such as Whole Trait Theory examined (a) whether within-person variability in two broad personality traits Extraversion and Neuroticism is consistently predicted by daily events, (b) whether positive and negative affect, respectively partly mediate this relationship and (c) the lagged relationships between events, and next day variations in affect and personality. Results revealed that personality exhibited significant within-person variability, that positive and negative affect partly mediate the relationship between events and personality, affect accounting for up to 60% of the effects of events on personality. Additionally, we identified that event-affect congruency was accountable for larger effects compared to event-affect non-congruency.

In article number 1700786, Dongeun Huh and co‐workers present a micro‐engineered model of the human placental barrier for investigation of maternal–fetal drug transfer in pregnancy. The placenta‐on‐a‐chip system reconstitutes efflux transporter‐mediated transport of a test compound, demonstrating proof‐of‐principle for use as a screening platform for prediction of drug transport in pregnancy.

The current lack of knowledge about the effect of maternally administered drugs on the developing fetus is a major public health concern worldwide. The first critical step toward predicting the safety of medications in pregnancy is to screen drug compounds for their ability to cross the placenta. However, this type of preclinical study has been hampered by the limited capacity of existing in vitro and ex vivo models to mimic physiological drug transport across the maternal–fetal interface in the human placenta. Here the proof‐of‐principle for utilizing a microengineered model of the human placental barrier to simulate and investigate drug transfer from the maternal to the fetal circulation is demonstrated. Using the gestational diabetes drug glyburide as a model compound, it is shown that the microphysiological system is capable of reconstituting efflux transporter‐mediated active transport function of the human placental barrier to limit fetal exposure to maternally administered drugs. The data provide evidence that the placenta‐on‐a‐chip may serve as a new screening platform to enable more accurate prediction of drug transport in the human placenta. This paper presents a microengineered model of the human placental barrierfor investigation of maternal–fetal drug transfer in pregnancy. The placenta‐on‐a‐chip system reconstitutes efflux transporter‐mediated transport of a test compound, demonstrating proof‐of‐principle for use as a screening platform for prediction of drug transport in pregnancy.