The advent of organ-on-chip (OOC) technology has disrupted biomedical research and offers unprecedented opportunities to study human organ systems in vitro with remarkable precision.
According to BIS Research, the global organ market is forecast to reach USD 3,596.3 million by 2033 from USD 109.9 million in 2023, growing at a CAGR of 42.09% during the forecast period 2024-2033.
These microfluidic devices, which simulate the physiological reactions of human organs, can replace traditional cell cultures and animal experiments, resulting in faster, more reliable drug development and personalized medicine.
However, the development of miniaturized organ models presents several challenges that must be overcome to realize the full potential of organ-on-a-chip technology.
Reproduction of complex organ functions
One of the primary challenges in developing miniaturized organ models is replicating the complex functions of human organs. Human organs are complex systems composed of several cell types, each of which performs a specific role in a highly coordinated manner. Mimicking this complexity on a chip requires precise control of cell positioning, differentiation, and interaction.
Advances in stem cell technology and 3D bioprinting have greatly contributed to addressing this challenge, enabling the creation of heterogeneous tissues that more closely resemble those found in the human body.
Stem cells, especially induced pluripotent stem cells (iPSCs), can differentiate into any cell type, making them ideal for generating different cell populations within organ models. 3D bioprinting technology, on the other hand, enables the construction of complex tissue architectures by depositing cells layer by layer in a precise pattern.
Together, these technologies have made significant progress in reproducing the cellular diversity and spatial organization of human organs.
Placenta-on-a-Chip model
Nicole Hashemi, a mechanical engineer at Iowa State University, developed a placenta-on-a-chip to model the placenta and understand how substances like caffeine move across it during pregnancy.
This innovation uses microfluidic technology to simulate the movement of fluid across the placenta, providing insight into the effects of drugs and toxins.
A silicon-on-a-chip placenta with microchannels mimics maternal and fetal blood flow, allowing researchers to study the effects of materials on the fetal side. Supported by a $350,000 NSF grant, this model could develop pregnancy studies, predict the effects of unknown drugs and toxins, and customize treatment options.
Integration of mechanical and biochemical signals
Another major challenge is the integration of mechanical and biochemical signals that are crucial for organ function. Human organs are subjected to various physical forces, such as shear stress in the liver caused by blood flow or cyclic stretching of the lungs.
These mechanical signals are essential for maintaining tissue homeostasis and function. In addition, organs are exposed to a variety of biochemical signals, including hormones, cytokines, and growth factors, that regulate cell behavior.
To address this challenge, researchers have developed microfluidic systems capable of recreating the dynamic environment of human organs. These systems use fluid flow to mimic blood circulation, allowing for continuous delivery of nutrients and removal of waste products.
They can also apply mechanical forces, such as stretching or compression, to the cells grown on the chip. By incorporating these physical and biochemical signals, organ-on-a-chip devices can more accurately reproduce the in vivo conditions of human organs.
NIST for drug testing
NIST is leading a task force to develop standards for organ-on-a-chip research, which involves creating microfluidic devices that mimic human organs to test drugs. These devices provide a controlled environment for studying tissue responses, offering an alternative to in vitro and in vivo testing.
A group of global researchers from industry, academia, and government aims to standardize protocols, measurements, and terminology to advance the field. Initial areas of focus are the heart, kidney and liver.
A workshop held at Michigan State University in April 2023 helped gather input from stakeholders. NIST’s neutrality facilitates collaboration and development of these standards.
Silk-based membranes improve accuracy in disease research
Duke University biomedical engineers have developed a new silk-based ultrathin membrane for organ-on-a-chip (OOC) platforms that better mimics human extracellular membranes, improving the accuracy of disease research.
Conventional polymer membranes are thicker and limit cell communication and growth, while the new silk fibroin membrane is less than five microns thick, closely resembling natural extracellular matrices. This development allows cells to form more realistic tissue structures, improving disease modeling and therapeutic testing.
When applied to kidney chip models, the membrane promoted cell differentiation and efficient molecular screening, promoting kidney disease research and potential drug screening. The technology can improve models of other organs, including the brain, liver and lungs. The study was published in The development of science.
Ensuring physiological relevance
Another critical challenge is ensuring the physiological relevance of miniaturized organ models. For organ-on-chip devices to be useful, they must faithfully reproduce the physiological and pathological processes of human organs.
This requires not only the re-creation of the cellular and mechanical environment, but also the precise modeling of the organ’s response to various stimuli, such as drugs or diseases.
One approach to increase physiological relevance is the use of patient-specific cells derived from iPSCs. These cells can be used to create personalized organ models that reflect the genetic and phenotypic characteristics of each patient.
Such personalized models can provide valuable insights into patient-specific drug responses and disease mechanisms, paving the way to personalized medicine.
Moreover, researchers are increasingly focusing on the development of multi-organ systems capable of simulating the interactions between different organs.
The human body is an interconnected system, and the functioning of one organ often depends on the signals of others. Multi-organ systems can provide a more comprehensive understanding of how drugs or diseases affect the body as a whole, improving the predictive power of organ-on-a-chip technology.
Standardization and scalability
Standardization and scalability are also significant challenges in organo-chip technology. For these devices to be widely used in research and industry, standardized protocols are needed for their fabrication, operation, and validation.
Currently, there are significant differences in the design and production of organo-chip devices, which makes it difficult to compare the results of different tests and laboratories.
Efforts are underway to develop standardized guidelines and protocols for organ-on-a-chip technology. These include defining key performance indicators such as barrier integrity, cell viability, and functional indicators, as well as defining standardized materials and manufacturing methods. Standardization facilitates the reproducibility and comparability of results, accelerating the adoption of organ-on-a-chip technology.
Scalability is another critical issue, especially for high-throughput filtration applications. Traditional fabrication methods, such as soft lithography, are labor intensive and not easily scalable. Emerging technologies such as injection molding and automated microfluidic assembly hold promise for the large-scale production of organ-on-a-chip devices. In addition, integration of organ-on-a-chip platforms with automated imaging and data analysis systems may further increase their utility in high-throughput applications.
Regulatory and ethical considerations
Finally, regulatory and ethical considerations must be taken into account in order to successfully translate organ-on-a-chip technology into clinical and industrial settings.
Regulatory agencies such as the FDA should establish clear guidelines for the validation and use of organs-on-chips in drug development and safety testing. These guidelines should address issues related to the reproducibility, reliability, and predictive value of organ-chip models.
Ethical considerations also play a crucial role, especially when using cells and tissues of human origin. Ensuring informed consent and protecting donor privacy are essential for the ethical use of patient-specific cells. In addition, the development and use of organ-chip technology should be guided by the principles of equity and accessibility, ensuring that the benefits of this technology are available to all.
Conclusion
By overcoming these challenges, researchers can pave the way to more accurate, reliable, and widely accepted organ-on-a-chip platforms.
Organ-on-chip technology not only speeds up drug development and precision medicine, but also reduces the use of animal experiments, resulting in more humane and efficient biomedical research.
About the publisher: BIS Research is a global market intelligence, research and advisory firm focused on emerging technology trends that are likely to disrupt the market. His team consists of industry veterans, experts and analysts with diverse backgrounds in consulting, investment banking, government and academia.