Organs-on-chips (OoCs) are systems containing engineered or natural miniature tissues grown inside microfluidic chips. To better mimic human physiology, the chips are designed to control cell microenvironments and maintain tissue-specific functions. Combining advances in tissue engineering and microfabrication, OoCs have gained interest as a next-generation experimental platform to investigate human pathophysiology and the effect of therapeutics in the body. There are as many examples of OoCs as there are applications, making it difficult for new researchers to understand what makes one OoC more suited to an application than another. This Primer is intended to give an introduction to the aspects of OoC that need to be considered when developing an application-specific OoC. The Primer covers guiding principles and considerations to design, fabricate and operate an OoC, as well as subsequent assaying techniques to extract biological information from OoC devices. Alongside this is a discussion of current and future applications of OoC technology, to inform design and operational decisions during the implementation of OoC systems. Organs-on-chips are microfluidic systems containing miniature tissues with the aim of mimicking human physiology for a range of biomedical and therapeutic applications. Leung, de Haan et al. report practical tips to inform design and operational decisions during the implementation of organ-on-a-chip systems. 

A guide to the organ-on-a-chip

https://www.nature.com/articles/s43586-022-00118-6.pdf

Polydimethylsiloxane (PDMS) is the predominant material used for organ-on-a-chip devices and microphysiological systems (MPSs) due to its ease-of-use, elasticity, optical transparency, and inexpensive microfabrication. However, the absorption of small hydrophobic molecules by PDMS and the limited capacity for high-throughput manufacturing of PDMS-laden devices severely limit the application of these systems in personalized medicine, drug discovery, in vitro pharmacokinetic/pharmacodynamic (PK/PD) modeling, and the investigation of cellular responses to drugs. Consequently, the relatively young field of organ-on-a-chip devices and MPSs is gradually beginning to make the transition to alternative, nonabsorptive materials for these crucial applications. This review examines some of the first steps that have been made in the development of organ-on-a-chip devices and MPSs composed of such alternative materials, including elastomers, hydrogels, thermoplastic polymers, and inorganic materials. It also provides an outlook on where PDMS-alternative devices are trending and the obstacles that must be overcome in the development of versatile devices based on alternative materials to PDMS.

Beyond Polydimethylsiloxane: Alternative Materials for Fabrication of Organ-on-a-Chip Devices and Microphysiological Systems.

The complex interaction of cells with biomaterials (i.e., materiobiology) plays an increasingly pivotal role in the development of novel implants, biomedical devices, and tissue engineering scaffolds to treat diseases, aid in the restoration of bodily functions, construct healthy tissues, or regenerate diseased ones. However, the conventional approaches are incapable of screening the huge amount of potential material parameter combinations to identify the optimal cell responses and involve a combination of serendipity and many series of trial-and-error experiments. For advanced tissue engineering and regenerative medicine, highly efficient and complex bioanalysis platforms are expected to explore the complex interaction of cells with biomaterials using combinatorial approaches that offer desired complex microenvironments during healing, development, and homeostasis. In this review, we first introduce materiobiology and its high-throughput screening (HTS). Then we present an in-depth of the recent progress of 2D/3D HTS platforms (i.e., gradient and microarray) in the principle, preparation, screening for materiobiology, and combination with other advanced technologies. The Compendium for Biomaterial Transcriptomics and high content imaging, computational simulations, and their translation toward commercial and clinical uses are highlighted. In the final section, current challenges and future perspectives are discussed. High-throughput experimentation within the field of materiobiology enables the elucidation of the relationships between biomaterial properties and biological behavior and thereby serves as a potential tool for accelerating the development of high-performance biomaterials.

High-Throughput Methods in the Discovery and Study of Biomaterials and Materiobiology

Electrochemical Sensing Directions for Next-Generation Healthcare: Trends, Challenges, and Frontiers.

We see affordability as a key challenge in making organs-on-chips accessible to a wider range of users, particularly outside the highest-resource environments. Here, we present an approach to barrier-on-a-chip fabrication based on double-sided pressure-sensitive adhesive tape and off-the-shelf polycarbonate. Besides a low materials cost, common also to PDMS or thermoplastics, it requires minimal (€ 100) investment in laboratory equipment, yet at the same time is suitable for upscaling to industrial roll-to-roll manufacture. We evaluate our microhpysiological system with an epithelial (C2BBe1) barrier model of the small intestine, studying the biological effects of permeable support pore size, as well as stimulation with a common food compound (chili pepper-derived capsaicinoids). The cells form tight and continuous barrier layers inside our systems, with comparable permeability but superior epithelial polarization compared to Transwell culture, in line with other perfused microphysiological models. Permeable support pore size is shown to weakly impact barrier layer integrity as well as the metabolic cell profile. Capsaicinoid response proves distinct between culture systems, but we show that impacted metabolic pathways are partly conserved, and that cytoskeletal changes align with previous studies. Overall, our tape-based microphysiolgical system proves to be a robust and reproducible approach to studying physiological barriers, in spite of its low cost.

/pdf/low-cost-microphysiological-systems-feasibility-study-of-a-z5zhtclcg9.pdf

Low-cost microphysiological systems: Feasibility study of a tape-based barrier-on-chip system for small intestine modeling

We see affordability as a key challenge in making organs-on-chips accessible to a wider range of users, particularly outside the highest-resource environments. Here, we present an approach to barrier-on-a-chip fabrication based on double-sided pressure-sensitive adhesive tape and off-the-shelf polycarbonate. Besides a low materials cost, common also to PDMS or thermoplastics, it requires minimal (€100) investment in laboratory equipment, yet at the same time is suitable for upscaling to industrial roll-to-roll manufacture. We evaluate our microphysiological system with an epithelial (Caco-2/BBe1) barrier model of the small intestine, studying the biological effects of permeable support pore size, as well as stimulation with a common food compound (chili pepper-derived capsaicinoids). The cells form tight and continuous barrier layers inside our systems, with comparable permeability but superior epithelial polarization compared to Transwell culture, in line with other perfused microphysiological models. Permeable support pore size is shown to weakly impact barrier layer integrity as well as the metabolic cell profile. Capsaicinoid response proves distinct between culture systems, but we show that impacted metabolic pathways are partly conserved, and that cytoskeletal changes align with previous studies. Overall, our tape-based microphysiological system proves to be a robust and reproducible approach to studying physiological barriers, in spite of its low cost.

/pdf/low-cost-microphysiological-systems-feasibility-study-of-a-18kdtbafxb.pdf

Low-cost microphysiological systems: feasibility study of a tape-based barrier-on-chip for small intestine modeling

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Low-cost microphysiological systems: Feasibility study of a tape-based barrier-on-chip system for small intestine modeling

Low-cost microphysiological systems: feasibility study of a tape-based barrier-on-chip for small intestine modeling