Can organ

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What happens when microtechnology and biology come together? We get organ-on-a-chip (OOC).

Organ-on-a-chip is a unique and innovative technology that aims to recreate the structure and function of tissues and organs on a miniature device or chip. The tissue or organ itself can either be engineered or naturally acquired and is grown inside a microfluidic chip.

This technology holds great promise to revolutionize biomedical research and provide an alternative to traditional animal testing. However, the research on this technology is still in its infancy.

Animal testing has been used for a long time in scientific research, as well as in cosmetic testing and drug development. However, it raises significant ethical concerns due to the suffering and harm caused to animals.

Wynn Institute/Harvard University

Additionally, since human and animal physiology is not identical, there are limitations associated with using animal models for humans. This discrepancy can lead to issues while predicting the efficacy and safety of products.

So now the real questions are, is OOC technology a better replacement for animal testing and can it speed up drug development?

Here, we explore the possibilities for using OOC technology for testing purposes, where the technological development in the field is headed, and the limitations holding up progress.

OOC technology integrates microtechnology, biology, and engineering principles to create functional tissue models. These chips are typically made of transparent materials and consist of microfluidic channels lined with living cells.

The creation of OOC devices typically involves the fabrication of the chip using microfabrication techniques, followed by preparing cell cultures which are then integrated into the microfluidic channels of the chip.

Mikael Häggström, M.D./Wikimedia Commons

Once the sample is ready, a dynamic environment is created to establish fluid flow, and mechanical forces are applied to mimic the organ's environment. OOC devices also have sensors attached to them, which help monitor various parameters such as viability, metabolism, and electrical activity of the organ.

By providing a three-dimensional environment that mimics the native tissue and organ action, OOC technology allows cells to interact and communicate much in the same way that they do in actual organ systems.

Broadly speaking, there are two types of OOC technology, depending on the number of organs on the chip — single-organ and multi-organ OOC systems.

Single-organ OOC systems consist of a single organ and are incredibly helpful for exploring the function of individual organs. However, individual organ function is also impacted by other organs, which is why it is also vital to study multi-organ OOC systems.

One early concept of a multiple-organ system on a chip was studied by Kwanchanok Viravaidya, Aaron Sin, and Michael L. Shuler in 2004. Their OOC device was a combination of four compartments, representing the lung, fat, liver, and other tissues.

NCATS/Wikimedia Commons

However, one of the big breakthroughs in OOC technology was led by Donald Ingber from the Wyss Institute for Biologically Inspired Engineering at Harvard University. In 2010, Ingber and his team developed the first successfully micro-engineered lung-on-a-chip.

But how is OOC technology different from traditional cell cultures?

Traditional cell or tissue cultures are used to grow and study cells in a laboratory. These methods involve growing cells on two-dimensional surfaces such as petri dishes or cell culture flasks, typically in a liquid medium containing essential nutrients and growth factors.

The term "tissue culture" was coined by American pathologist Montrose Thomas Burrows and has been around since the 1800s. However, recent advances in OOC technology allow it to surpass traditional cell cultures in many different aspects.

OOC technology allows researchers to mimic the complex three-dimensional structures and micro-environments of human organs which is often physiologically more relevant than the two-dimensional environment of cell cultures.

kaibara87/Wikimedia Commons

Three-dimensional cell culture techniques include scaffolding and bioprinting. These have already been used for drug discovery and have replaced some animal testing. However, they also have limitations, such as the presence of unwanted human-derived hormonal components. They can also suffer from batch-to-batch variability and other limitations.

OOC avoids these issues and also offers the advantage of utilizing microchips to study organ function on a miniature scale.

Another advantage that OOC offers is the ability to recreate tissue-tissue interfaces. By allowing the integration of multiple cell types, OOCs can help us to study cellular cross-talk, cell signaling, and the influence of different cell populations on overall organ function.

Additionally, OOC technology offers the ability to create dynamic conditions. The chips can simulate physiological conditions such as fluid flow, mechanical forces, and biochemical gradients. These are much more challenging to replicate in three-dimensional cell cultures, although researchers are still working to develop such systems.

Lastly, OOC technology offers the ability to test and analyze the effect of multiple drugs or compounds in parallel. This enhances efficiency, reduces costs, and can accelerate the pace of drug discovery and testing.

All these advantages make OOC a great candidate for use in biomedical research, potentially leading to more accurate and efficient methods for studying diseases, developing drugs, and assessing toxicity.

The use of animals for drug development, testing cosmetic formulations, and other similar uses has long been a highly contentious issue for a variety of reasons. One of them is the ethical concerns of using animals for our use. Animals are often treated poorly and are almost always severely harmed or killed during testing, causing them extreme distress, pain, and suffering.

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This raises serious ethical questions about the moral and humane treatment of animals and the balance between animal rights and human benefits. Many societies and organizations, such as The Physicians Committee for Responsible Medicine (PCRM) and People for the Ethical Treatment of Animals (PETA), have been fighting to end all animal testing.

Aside from the ethical concerns, there are limitations associated with the use of animal models in predicting human responses. While the basic biological mechanisms are similar, humans are genetically and physiologically very different from animals.

As Donald Ingber said in an interview with Nature Reviews Materials, "Animal models are commonly used to study human diseases and treatments; however, they are often limited in their ability to mimic human conditions, in particular, on the molecular and cellular levels. Why are we still using them?"

The differences in drug metabolism, disease manifestation, and immune responses mean that the safety and efficacy of a drug tested on animals will not necessarily translate to humans.

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Moreover, the high costs and time-consuming nature of animal testing pose significant challenges. Animal testing requires a large number of animals that need to be housed, provided with veterinary care, and fed. Additionally, there are lengthy experimental protocols and regulations which must be followed, which add to the expense and time.

Alternative methods to end animal testing, such as in virto testing, earlier human trials, and computational modeling, are being explored, but all have a number of limitations. And organ-on-a-chip could not have come at a better time!

Given the success of OOC technology and the current limitations and ethical considerations surrounding animal testing, it is highly likely that OOC devices will eventually replace or eliminate the need for animal testing.

OOC technology is highly accurate and offers enhanced predictability due to its excellent recreation of the function of various human organs, thus making it a far better candidate for studying human-specific responses to toxins, diseases, and drugs over animals.

This, in turn, reduces the time and cost spent on preclinical testing and reduces the risk of adverse effects when the findings are translated to human subjects.

Andrii Koval

Additionally, OOC technology can be used to test multiple compounds and drugs in parallel on a single chip, massively streamlining the drug development and discovery process. This efficiency reduces the time and financial burden associated with animal testing, allowing researchers to expedite scientific research.

Moreover, OOC technology doesn't harm or mistreat animals as the cells or tissues are human-derived (humans are not harmed either). This approach pretty much eliminates animal suffering, giving an enormous win to animal rights and welfare.

The future progress of organ-on-a-chip (OOC) technology is highly promising. Since the breakthrough in 2010, other organs, such as the liver, heart, and kidney, have been successfully recreated using OOC technology. These advancements have enabled researchers to study organ functions, interactions, and responses to drugs and diseases with greater precision and relevance.

In 2012, another study by Ingber and his team explored drug toxicity in a lung-on-a-chip micro-device. Liver-on-a-chip models have also shown promise in drug metabolism studies and toxicity testing.

Wyss Institute, Harvard University/Wikimedia Commons

Heart-on-a-chip models have also been successfully developed. A study led by Genevieve Conant, from the University of Toronto, used a heart-on-a-chip model to assess cardiac function and screen candidates for drug toxicity.

Multiple organ models have also been developed, including gut on a chip, an intestine-kidney chip, and small intestine, liver, and lung on a chip. These multi-organ chips hold great promise for investigating drug effects on multiple systems and have already been used to test pharmacokinetics of anticancer drugs, host-gut microbiota cross talk, and nutrition metabolism.

Despite the success stories, there are ongoing challenges and limitations with OOC technology. Since the technology is still in its early stages, more funding, research, and development are needed for its wider adoption.

Validation of these models against clinical data is also crucial to ensure their accuracy and reliability. Standardization of OOC platforms, integration of a wider range of multiple organ systems, and long-term culture viability are areas that require further attention.

Ongoing research is also focused on expanding and refining the capabilities of OOC devices, such as incorporating immune cells, vasculature, and multi-organ systems. Further integration with imaging techniques will offer these devices an advantage by enabling real-time monitoring.

University of Washington/Wikimedia Commons

The need for multi-organ OOC systems, in particular, is essential, as organs are part of many networks in the body.

OOC technology represents a paradigm shift in drug discovery and development, offering a more accurate, efficient, and humane approach to studying human physiology and developing safe and effective treatments. By leveraging the power of engineering, microtechnology, and biology, OOC devices are paving the way for a future where animal testing can be replaced or entirely eliminated, leading to significant advancements in drug discovery and toxicity testing without the need to harm animals!