What is organ-on-chip technology used for?

Organ-on-chip (OoC) technology bridges the gap between standard 2D-cell culture and very complex animal models. While conventional cell culture doesn’t replicate the complexity of organs in vivo, animal models often don’t yield results that are relevant to humans.

OoC models on the other hand simulate the physiology of human organs, the molecular processes of the human body and biomechanical cues on a biochip. Organ models are therefore well suited for the areas of research and development that require both human cells as well complex systems.

Some of the fields that contribute from organ-on-chip are therefore preclinical drug development, research of inflammation and chronic diseases, disease and infection modelling, cancer research and personalized medicine.

At last, researchers have an alternative to working with mice or other animals, which is not only ethically concerning but also costly and bureaucratic.

What are the research fields that contribute the most from OoC technology?

Preclinical drug development

Drug discovery is the process leading from target discovery up to the regulatory approval of a new drug. It involves drug discovery and development, pre-clinical research, clinical research as well as regulatory review and post-market surveillance (Fig. 1). The drug development process is an extensive and expensive process that can take on average 10 to 15 years from target research to final drug on the market and amounts to around 0.7 to 2.7 billion US dollars (Rousseaux 2023 et al.). Typically, only 1 out of 5,000 – 10,000 potential drugs from drug discovery will reach approval by the health authorities (Rousseaux 2023 et al.). According to Sun 2022 et al. the 90% of drugs failing after clinical trial phase 1 are due to lack of clinical efficacy (40%–50%), unmanageable toxicity (30%), poor drug-like properties (10%–15%), and lack of commercial needs and poor strategic planning (10%).

This means that using more relevant preclinical models could potentially avoid 30 to 80% of drug failures in phase 1. The primary aim of this phase is to identify drugs that may be toxic to the human body and determine an ideal starting dosage before clinical trials begin. This assessment of toxicity is done using in vitro and in vivo methods. If a drug shows signs of toxicity in the model system, it is removed from the trial and not considered for further studies.

Standard in vitro models can be run in high throughput but are less complex and can therefore only provide a first indication of a drug’s safety. Animal models, on the other hand, often fail to replicate human results in terms of dosage and toxicity, leading to the failure of clinical trials. Such failure can partly be explained by the species differences existing between humans and animals.

Organ models can be an alternative, that not only allows the reduction of animal use in pharma (3R principle) but also provides human relevant prediction on toxicity and dosage.

There is just one caveat when choosing a OoC system for drug testing, the choice of biochip material is important. While most of the systems can deliver comprehensive results for hepatoxicity they are all made from different materials and some show very high compound adsorption rates such as PDMS. At Dynamic42 we provide biochips made of a unique medical-grade plastic, ensuring biocompatibility and low drug adsorption even of very hydrophobic compounds.

Would like to learn more about adsorption of drugs by biochips? Read this blog.

Research of inflammation and chronic diseases

Autoimmune diseases, such as rheumatoid arthritis and inflammatory bowel disease, develop when the adaptive immune system no longer tolerates self-antigens and instead establishes an immune response against them. Autoimmune diseases can affect almost all organs (Mello 2019 et al.). Triggers are complex but usually involve a combination of genetic and environmental factors. Due to their complex nature, most, inflammatory diseases cannot faithfully be replicated in animal models, creating the need for physiological human in vitro models to advance research in this field. Immunocompetent organs-on-chip offer a potent model to study chronic inflammatory processes, paving the way for a deeper understanding of these diseases and the development of targeted therapies. At Dynamic42, we have developed a colitis-on-chip model that simulates characteristics of inflammatory bowel disease observed in vivo (Figure below).

Accurate disease modelling

OoC models are capable of replicating human-specific pathophysiology and multi-organ interactions in a controlled microenvironment. Unlike 2D cultures, OoC systems integrate biomechanical cues like fluid shear stress and the 3D tissue architectures that mimic organ-level functions.  Animal models on the other hand often fail to predict human immune responses due to species-specific differences in cellular receptors, signaling pathways, and drug metabolism. OoC platforms overcome this by using patient-derived iPSCs and primary human immune cells to model human-specific targets. They can also include vascularization for studying immune invasion or dynamic drug applications. They allow for real-time monitoring, giving an indication for oxygen levels and the barrier integrity of a tissue or organ during a treatment or disease state.

OoC will be particularly interesting for the future medicine where we develop compounds that are targeting one specific molecule. For example, antibodies targeting a tumor or other diseased cells. Those targets will rarely be conserved in animals. Therefore, there is a need to find new ways to screen compounds in a human-relevant system for function of these drugs and therapies.

Infection modelling

Infectious disease research helps us understand the interactions between pathogens, their host and (if relevant) the naturally occurring microbiota. 2D cell culture lacks the structural complexity and fails to model tissue barrier (e.g., epithelial-endothelial interfaces) cross-talks. Microfluidic systems in OoC devices provide precise control over biochemical gradients, oxygen levels, and flow conditions, which are essential for creating in vivo like tissue barriers and cross-talks for infection studies. Organ models are therefore well suited to mimic how pathogens invade tissues or colonize niches, as well as how tissues respond to such insults. They also offer a spatially controlled environment to co-culture human cells with commensal or pathogenic microbes, such as in Kaden et al. (2024) or Hoang et al. (2022). Importantly, they can also model immune cell recruitment, such as neutrophil migration, macrophage activation or cytokine response like done in Maurer et al. (2019).

Real-time monitoring in OoC technology allows for tracking of the infection progression and immune responses using integrated sensors, such as TEER for barrier integrity.

While 2D cultures cannot replicate the complex dynamics in vivo, animal models often fail to mimic human-specific pathogen tropism or immune responses. Animal models suffer from species-specific differences in several biological aspects including immune pathways and microbiome composition, therefore limiting their translational relevance. Organ models use human-derived cells, including patient-specific immune cells (T cells, macrophages) and stromal cells to model individualized responses, thus offering new perspectives to personalized medicine. They can also include vascularization to mimic immune cell invasion, a feature practically not achievable with 2D culture.

At Dynamic42, we have put strong emphasis on developing cutting-edge infection models that shed light on the complex mechanisms underlying infectious diseases. If you would like to learn more about infection research done with organ models, you can find some examples in this blog.

Cancer research & personalized medicine

Cancer research and diagnostics benefit significantly from OoC technology. Early tumor detection and risk assessment require examination of individual cellular materials, such as gastrointestinal, lung, or skin cells, in an environment similar to the human body. OoC allows cells to thrive in such conditions, providing accurate diagnostic images.

A critical focus is modelling the tumor microenvironment (TME), particularly for immunotherapy advancements. The TME significantly influences an individual’s immune profile through the creation of an immunosuppressive milieu, ultimately impacting the response of the immune system to cancer cells. Current preclinical models struggle to replicate human-specific biophysical/biochemical factors (e.g., immune cell interactions, stromal composition), limiting immunotherapy predictability. Microphysiological models mimicking patient-specific TME, including immune components, are now enabling personalized drug screening. For example, Dynamic42’s pancreatic cancer spheroid-on-a-chip integrates patient-derived fibroblasts and TME elements, offering immunocompetent platforms for tailored therapies.

Organ-on-chip models divide into two major groups – single-organ systems and multi-organ systems. Multi-organ models interconnected two or more single-organ models to reproduce the interactions and metabolic pathways that occur in vivo. This is particularly interesting to simulate metastasis in cancer models or the metabolization of drugs that are taken up by the lung or intestine and then further processed by the liver.

Conclusion

Organ-on-Chip technology benefits a wide range of users in biotech, pharma or academia to develop new drugs, address fundamental scientific research questions and uncover novel biological phenomena and mechanisms. Scientists now have the opportunity to incorporate organ models into their research to investigate molecular mechanisms under biologically human-relevant conditions such as multicellular interactions, perfusion, pathogen-host interactions, and biomechanical stimulation. Organ models certainly bridge the gap between standard cell culture and animal models, to provide us with more human relevant research insights in the years to come.

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