Microphysiological Systems: Approaches, Applications and Opportunities – Technology Networks

Microphysiological systems (MPS), also commonly referred to as organ-on-a-chip or body-on-a-chip technologies, have gained considerable attention in recent years. They provide a more physiologically relevant setting compared to static two-dimensional cell culture assays or animal models, as they more closely recapitulate human physiology and the downstream effects of drugs on multiple tissues. The development of MPS technologies has been driven by advances in several areas 3D cell culture techniques, microfluidics, tissue engineering and bioprinting enabling the creation of various key components. In this article, we highlight advances in the field that have been instrumental to the development of MPS, as well as key applications and future opportunities.

However, building a device that encompasses several tissue constructs to produce an interconnected multi-organ environment is no easy feat, as Dokmeci explains, Finding a universal media that satisfies the needs of multiple cells or organs is one of the main challenges.

Also, being able to control the fluid flow between different systems sometimes requires microvalves, which enables automation but complicates the design and manufacturing of the system. Overall, adding more components complicates the design, he adds.

In recent years, there have been efforts to improve the in vitro models used in preclinical drug development and disease research. In particular the use of microphysiological systems (MPS), also sometimes referred to as organ-on-a-chip (OOC) technologies, has become more widespread. Download this app note to discover a gut MPS that has physiologically relevant morphology, reduced barrier integrity and mucus expression. It can also be used to predict drug permeability across an intestinal barrier.

To prevent loss of the drug compounds, the team chose to assemble their MPS using polymethyl methacrylate (PMMA) rather than polydimethylsiloxane (PDMS). While PDMS has been widely used to build microfluidic chips until now, it can cause small molecules to be absorbed into the walls of the chip, reducing the free concentration of drug within the circulated medium, affecting drug bioavailability.

Atala explains that to create the MPS they employed strategies like those used to implant engineered tissues in patients. We first determine the major cell types present in the specific organ, and we use normal cells in the same proportions as present in humans. We also use the tissue-specific glue that holds cells together, the extracellular matrix, he says. The team then combined the different organoids of interest into a single system by immobilizing them in hydrogels within individual chambers.

Atala elaborates, We can therefore test many parameters, such as the effects of one drug on a specific organ, and how the drug gets metabolized and processed, or its bystander effects on other organs. The system, depending on how many tissues it uses, can be designed to fit an area about the size of a matchbox.

This is one of the main promises of the organ-on-a-chip field being able to borrow cells from patients and test the drugs on individual patients beforehand, explains Dokmeci.

The invention of induced pluripotent stem cells (iPSCs) has helped to expedite research in this field, he adds. Personalized MPS can be created using blood samples, primary human tissue and cells derived from iPSCs, as Dokmeci emphasized above.

There are efforts by different groups in this area, explains Prof. Nureddin Ashammakhi, ex-associate director of the Center for Minimally Invasive Therapeutics, UCLA. Ashammakhis research is focused on 3D bioprinting and the development of organ-on-a-chip models for regenerative and personalized medicine.

In a recent study, published in Bio-Design and Manufacturing, Ashammakhi and colleagues reviewed the development of lung MPS to model the pathology of COVID-19. According to Ashammakhi, when designing a lung MPS it is important to mirror the organs unique organization and function.

This is achieved by designing a chip with one chamber for air, representing alveolus and one chamber lined with endothelial cells, representing the blood vessel. The two chambers are separated by a porous membrane that allows the movement of molecules between the two sides, says Ashammakhi.

It is even possible to emulate the motion of in vivo breathing by applying a vacuum to chambers surrounding the epithelialcapillary membrane, causing it to stretch. This is an important element as stress has been shown to influence permeability of the membrane and the release of reactive oxygen species, as well as other molecules.

COVID-19 pathology can be organized into the following stages: SARS-CoV-2 viral entry by the ACE2 receptor; inflammation or malfunction of the innate immune response; coagulopathy or clotting dysregulation; edema or swelling and fluid accumulation; and fibrosis or scarring through the buildup of fibrotic connective tissue, explains Ashammakhi.

While there are surely benefits to assessing COVID-19 using a single lung-on-a-chip device, as Ashammakhi eludes above, the systemic nature of the disease means that a multi-organ MPS would be needed to reflect secondary and systemic effects of the drugs being tested. The inclusion of other cell types such as immune cells is also of utmost importance in developing relevant models especially for infection-related studies, he stresses.

AI is very important in this sense, it can make the big data obtained from multiple MPS chips, for a multitude of variables comprehendible relations [can be] identified and conclusions can be drawn, says Ashammakhi.

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Microphysiological Systems: Approaches, Applications and Opportunities - Technology Networks