Skin allergy, in particular, allergic contact dermatitis and irritant contact dermatitis, are common occupational and environmental health problems affecting the quality of life of a significant proportion of the world population. Since all new ingredients to be incorporated into a product are potential skin allergens, it is essential that these ingredients be first tested for their allergenic potential. However, despite the considerable effort using animal models to understand the underlying mechanism of skin sensitization, to date, the molecular and cellular responses due to skin contact with sensitizers are still not fully understood. To replace animal testing and to improve the prediction of skin sensitization, significant attention has been directed to the use of reconstructed organotypic in vitro models of human skin. Here we describe a miniaturized immune competent in vitro model of human skin based on 3D co-culture of immortalized human keratinocytes (HaCaT) as a model of the epidermis barrier and human leukemic monocyte lymphoma cell line (U937) as a model of human dendritic cells. The biological model was fitted in a microfluidic-based cell culture system that provides a dynamic cellular environment that mimics the in vivo environment of skin. The dynamic perfusion of culture media significantly improved the tight junction formation as evidenced by measuring higher values of TEER compared to static culture. This setting also maintained the high viability of cells over extended periods of time up to 17 days. The perfusion-based culture also allows growth of the cells at the air-liquid interface by exposing the apical side of the cells to air while providing the cell nutrients through a basolateral fluidic compartment. The microsystem has been evaluated to investigate the effect of the chemical and physical (UV irradiation) stimulation on the skin barrier (i.e. the TJ integrity). Three-tiered culture differential stimulation allowed the investigation of the role of the keratinocyte layer as a protection barrier to chemical/biological hazards.

This focus article introduces the concept of NutriChip, an integrated microfluidic platform for investigating the potential of the immuno-modulatory function of dairy food. The core component of the NutriChip is a miniaturized artificial human gastrointestinal tract (GIT), which consists of a confluent layer of epithelial cells separated from a co-culture of immune cells by a permeable membrane. This setting creates conditions mimicking the human GIT and allows studying processes that characterize the passage of nutrients though the human GIT, including the activation of immune cells in response to the transfer of nutrients across the epithelial layer. The NutriChip project started by developing a biologically active in vitro cellular system in a commercial Transwell co-culture system. This Transwell system serves as a reference for the micro-scale device which is being developed. The microfluidic setup of NutriChip allows monitoring of the response of immune cells to pro-inflammatory stimuli, such as lipid polysaccharide (LPS), and to the application of potentially anti-inflammatory dairy food. This differential response will be quantified by measuring the variation in expression of pro-inflammatory cytokines, including interleukin 1 (IL-1) and interleukin 6 (IL-6), secreted by the immune cells, and this is achieved by using a dedicated optical imager. A series of dairy products will be screened for their anti-inflammatory properties using the NutriChip system and, finally, the outcome of the NutriChip will be validated by a human nutrition trial.Therefore, the NutriChip platform offers a new option to evaluate the influence of food quality on health, by monitoring the expression of relevant immune cell biomarkers.

Organ-on-a-chip (OOC) is a very ambitious emerging technology with a high potential to revolutionize many medical and industrial sectors, particularly in preclinical-to-clinical translation in the pharmaceutical arena. In vivo, the function of the organ(s) is orchestrated by a complex cellular structure and physiochemical factors within the extracellular matrix and secreted by various types of cells. The trend in in vitro modeling is to simplify the complex anatomy of the human organ(s) to the minimal essential cellular structure “micro-anatomy” instead of recapitulating the full cellular milieu that enables studying the absorption, metabolism, as well as the mechanistic investigation of drug compounds in a “systemic manner.” However, in order to reflect the human physiology in vitro and hence to be able to bridge the gap between the in vivo and in vitro data, simplification should not compromise the physiological relevance. Engineering principles have long been applied to solve medical challenges, and at this stage of organ-on-a-chip technology development, the work of biomedical engineers, focusing on device engineering, is more important than ever to accelerate the technology transfer from the academic lab bench to specialized product development institutions and to the increasingly demanding market. In this paper, instead of presenting a narrative review of the literature, we systemically present a synthesis of the best available organ-on-a-chip technology from what is found, what has been achieved, and what yet needs to be done. We emphasized mainly on the requirements of a “good in vitro model that meets the industrial need” in terms of the structure (micro-anatomy), functions (micro-physiology), and characteristics of the device that hosts the biological model. Finally, we discuss the biological model–device integration supported by an example and the major challenges that delay the OOC technology transfer to the industry and recommended possible options to realize a functional organ-on-a-chip system.

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