Obesity and its numerous adverse health consequences have taken on global, pandemic proportions. White adipose tissue (WAt)-a key contributor in many metabolic diseases-contributes about one fourth of a healthy human's body mass. Despite its significance, many WAT-related pathophysiogical mechanisms in humans are still not understood, largely due to the reliance on non-human animal models. In recent years, Organ-on-a-chip (OoC) platforms have developed into promising alternatives for animal models; these systems integrate engineered human tissues into physiological microenvironment supplied by a vasculature-like microfluidic perfusion. Here, we report the development of a novel OoC that integrates functional mature human white adipocytes. The WAT-on-achip is a multilayer device that features tissue chambers tailored specifically for the maintenance of 3D tissues based on human primary adipocytes, with supporting nourishment provided through perfused media channels. The platform's capability to maintain long-term viability and functionality of white adipocytes was confirmed by real-time monitoring of fatty acid uptake, by quantification of metabolite release into the effluent media as well as by an intact responsiveness to a therapeutic compound. The novel system provides a promising tool for wide-ranging applications in mechanistic research of WAtrelated biology, in studying of pathophysiological mechanisms in obesity and diabetes, and in R&D of pharmaceutical industry. The global obesity pandemic poses one of today's biggest challenges to public health. Each year, 2.8 million people die from causes related to overweight or obesity 1. Since the 1970s, the worldwide prevalence of obesity has nearly tripled, also leading to an upsurge in associated comorbidities such as type 2 diabetes (Fig. 1a) 2. Future projections reveal the gravity of this public health crisis: the prevalence rates of childhood obesity are increasing at an alarming pace 3 , and by 2030, more than 50% of U.S. adults are predicted to be obese 4. White adipose tissue (WAT) is the principal organ in obesity. In healthy human adults, WAT comprises approximately 20-25% of the total body mass, thus constituting the second largest organ, after the skin. In obese individuals, WAT's contribution to the total body mass may become as high as 50% (Fig. 1b) 5. WAT is tightly involved in the two most important functions of an organism-energy homeostasis and reproduction 6. In energy homeostasis, not only does WAT act as the main storage site of excess dietary energy (Fig. 1c), it also performs crucial endocrine and metabolic functions (Fig. 1d) 7,8. WAT can sense the body's energy status, and respond appropriately, either by storing fuel, in the form of triacylglycerides, or by releasing it as glycerol and fatty acids, for ultimate delivery to organs in need. While this classically described role of WAT already entailed extensive crosstalk between WAT and other organs, its inter-organ communications extend beyond simple feedback loops activated by fed-or fast...

Gene therapies using adeno-associated viruses (AAVs) are among the most promising strategies to treat or even cure hereditary and acquired retinal diseases. However, the development of new efficient AAV vectors is slow and costly, largely because of the lack of suitable non-clinical models. By faithfully recreating structure and function of human tissues, human induced pluripotent stem cell (iPSC)derived retinal organoids could become an essential part of the test cascade addressing translational aspects. Organ-on-chip (OoC) technology further provides the capability to recapitulate microphysiological tissue environments as well as a precise control over structural and temporal parameters. By employing our recently developed retina on chip that merges organoid and OoC technology, we analyzed the efficacy, kinetics, and cell tropism of seven first-and second-generation AAV vectors. The presented data demonstrate the potential of iPSC-based OoC models as the next generation of screening platforms for future gene therapeutic studies.

Obesity and associated diseases, such as diabetes, have reached epidemic proportions globally. In this era of "diabesity", white adipose tissue (WAT) has become a target of high interest for therapeutic strategies. To gain insights into mechanisms of adipose (patho-)physiology, researchers traditionally relied on animal models. Leveraging Organ-on-Chip technology, a microphysiological in vitro model of human WAT is introduced: a tailored microfluidic platform featuring vasculature-like perfusion that integrates 3D tissues comprising all major WAT-associated cellular components (mature adipocytes, organotypic endothelial barriers, stromovascular cells including adipose tissue macrophages) in an autologous manner and recapitulates pivotal WAT functions, such as energy storage and mobilization as well as endocrine and immunomodulatory activities. A precisely controllable bottom-up approach enables the generation of a multitude of replicates per donor circumventing inter-donor variability issues and paving the way for personalized medicine. Moreover, it allows to adjust the model's degree of complexity via a flexible mix-and-match approach. This WAT-on-Chip system constitutes the first human-based, autologous, and immunocompetent in vitro adipose tissue model that recapitulates almost full tissue heterogeneity and can become a powerful tool for human-relevant research in the field of metabolism and its associated diseases as well as for compound testing and personalized-and precision medicine applications.