The process of drug development and safety testing is extremely expensive and time-consuming. Animal testing is a vital part of drug development process, which is beneficial for researchers in understanding the cause, diagnosis and treatment of various medical conditions. However, there are several concerns over the validity of animal research; drugs that seem to be safe and effective in animals usually turn out to be harmful or ineffective in humans, as animal models often do not accurately reflect the human physiology. Due to this biological mismatch, several toxic drugs are subjected to costly clinical trials, while potentially useful drugs do not get commercialized. Until recently, it was observed that these models display unparalleled flexibility in simulating and studying the complicated and delicate interactions between various cell types and tissues in humans. This is demonstrated by the statistic that 80% of the medications intended to target human disorders successfully complete preclinical animal testing but fail to advance through the clinical stages. The global organ on a chip market is anticipated to grow at a CAGR of around 21%, till 2035. Driven by the efforts of various medical researchers for the use of these miniaturized platforms over the traditional animal testing models and the advancements of existing 3D models coupled with the role of FDA in building alliances with various industries and institutes working in this domain, the demand for developing organ-on-chip devices is likely to witness considerable growth in the coming years.
Organ-on-chips are the miniature copies of the vital human organs (such as liver, lungs, kidneys, intestines, and other vital organs), that have been developed by reasearchers / start-ups for several medical research and therapy development purposes. This 3D microfluidic cell culture device is made using microfabrication techniques and has chambers that are continually perfused with live cells to mimic the physico-chemical microenvironment of tissues in the human body. Further, in order to assess the feasibility of organ-on-chips over the traditional cell culture and animal-based testing methods, several scientists at the FDA are making efforts in evaluating the effectiveness of these systems in order to better understand the efficacy and toxicity of medications, foods, cosmetics, and dietary supplements.
CLASSIFICATION OF ORGAN-ON-CHIPS
Organ-on-chips have been broadly categorized into three types based on the function and nature of cells to be evaluated on the chip. The three types of organ-on-chips are- single organ chips, disease / therapeutic specific chips, and multi-organ-chips.
Single Organ Chips: Single organ chips mimic the physiology of a particular organ on a chip, such as the heart, liver, lung, and others. These systems frequently attain a high level of biological authenticity, enabling examination of how a particular organ reacts to a substance or mixture of substances.
Disease / Therapeutic Specific Chips: A number of microfluidic based disease specific chip models have been either developed or under development for use across different therapeutic areas. Cancer-on-chip or tumor-on-chip is a widely used model in oncology research and study the key aspects of human microenvironment. In addition, other microfluidic chip models that are under development, include rheumatoid arthritis-on-chip, cardiac fibrosis-on-chip, cardiac arrythmias-on-chip, and others.
Multi-Organ Chips: Given the several benefits of organ-on-chips and tumor-on-chip models in the research studies being conducted in pharmaceutical domain, multi-organ chips are next in line to being adopted by the researchers for testing certain therapies or for generalizing personalized medicine. ‘Multi-organ-chips’, often termed as the ‘human-on-a-chip’ and ‘body-on-a-chip’, provide a framework for investigating the potential interaction of one or more organs through the exchange of metabolites or soluble signaling molecules.
ADVANTAGES OF ORGAN-ON-CHIPS
§ Physiological Relevance: These systems mimic the microenvironment of human organs, allowing researchers to study tissue responses and interactions in a more physiologically relevant context.
§ Reduced Animal Testing: They can reduce the need for animal testing, offering more ethical and cost-effective alternatives for studying drug toxicity and efficacy.
§ Personalized Medicine: The can be customized with patient-specific cells, enabling personalized medicine approaches and drug testing tailored to individual genetic backgrounds.
§ High Throughput Screening: They can be used in high-throughput screening for drug discovery, accelerating the identification of potential drug candidates.
§ Disease Modeling: They can replicate disease conditions, providing valuable insights into disease mechanisms and enabling the development of targeted therapies.
§ Environmental Control: Researchers can precisely control the microenvironment of OOCs, including factors like oxygen levels, temperature, and nutrient supply, to mimic specific conditions accurately.
LIMITATIONS OF ORGAN-ON-CHIPS
§ Cell Source Variability: The source and quality of human cells used in them can vary, affecting the reliability and reproducibility of experimental results.
§ Limited Organ Complexity: Currently, they are mainly designed to mimic single organs or tissues, making it challenging to study interactions between multiple organs and systems in the body.
§ Long-term Viability: Maintaining cell viability and functionality in them for extended periods can be challenging, limiting their use for long-term studies or chronic disease modeling.
§ High Development Costs: Designing and fabricating of such devices can be expensive and require specialized expertise, which can limit their accessibility to researchers.
§ Ethical Concerns: While they reduce the need for animal testing, ethical concerns can still arise, particularly regarding the use of human cells and tissues in research.
§ Regulatory Hurdles: Regulatory agencies like the FDA are still developing guidelines for the use of device in drug development and safety testing, which can create uncertainties for their adoption in industry.
APPLICATIONS OF ORGAN-ON-CHIPS
The applications of these microfluidic chips in drug discovery and development processes have been described in detail below:
§ Replicating in vivo conditions: The ultimate goal of building any organ-on-chip model for drug development is to produce a translational in vitro model and understand the human disease pathogenesis. Despite attempts, achieving actual clinical translatability is still difficult.One way to transcend the translational barrier is to include tissue-specific environmental signals, such as flow and mechanical stress into microfluidic devices, thereby simulating the tissue microenvironment.
§ Evaluating drug safety and efficacy: Organ-on-chips are used to evaluate the safety of medications before they advance through clinical stages of development. In preclinical research, only 48% of the patients are subject to negative medication responses. This is partly because human medication toxicities are difficult to detect in routinely utilized preclinical organisms.
§ Incorporating immune cells: The immune system has an impact on a variety of diseases, including cancer, neurological problems, chronic infections, and autoimmune diseases.The ability to incorporate immune cells into organ-on-chip systems to simulate human-specific immune responses to immune-system-targeting therapies, such as biologics or cell therapies, will enable immunotoxicity assessments that are otherwise missed in in vivo models, due to the varying anatomy of the human and animal immune systems.
Owing to the potential of organ-on-chip models in simulating the architecture and function of human organs by combining 3D bioengineering constructs, several stakeholders have deployed organ-on-chip platforms to study the physical aspects of organisms. In fact, a number of studies are underway to assess the applicability of organ-on-chips in medical research and dispel the notion that animal testing is the only way to advance human health and safety. So far, research on these 3D models have enabled development of several microfluidic chips that can approximate the function of various organs, including liver, lungs, and gut in order to maintain various tissue-specific functions. In addition, cancer-on-chip models have emerged as a powerful tool in assessing the diagnostic and treatment outcomes and identify key molecular, cellular, and biophysical features of human cancer progression. Further, in order to validate the reliability of microfluidic devices for use across multiple application areas, researchers are still identifying ways to improve the key physiological monitoring parameters of these systems; one of these is the integration of sensors into the chips which will make the study of complex key aspects of human physiology relatively easier and convenient.
About Roots Analysis
Roots Analysis is a global leader in the pharma / biotech market research. Having worked with over 750 clients worldwide, including Fortune 500 companies, start-ups, academia, venture capitalists and strategic investors for more than a decade, we offer a highly analytical / data-driven perspective to a network of over 450,000 senior industry stakeholders looking for credible market insights. All reports provided by us are structured in a way that enables the reader to develop a thorough perspective on the given subject. Apart from writing reports on identified areas, we provide bespoke research / consulting services dedicated to serve our clients in the best possible way.