Organoid vs Organ On A Chip: A Comparative Review of Cutting-Edge In Vitro Models

What are organoids?

Organoids are stem cells that are programmed to differentiate and self-organize into spatially complex tissues or organs, in a 3D (3D) culture system, that are incredibly similar to a patient's body tissue or organ. Organoids aren't organs, but they're the closest thing to a real organ in shape and function, the closest vivisection of tissue shape and function, and they can be stable subcultured for years.

What is the process of organoid development?

The development of organoids is a complex and highly technical biological research task. Its core lies in simulating the structure and function of organs in vivo through 3D culture technology. First, it is necessary to select appropriate cell sources, such as stem cells (including pluripotent stem cells and adult stem cells) or specific types of adult cells, and isolate and cultivate cells based on the characteristics of the target organ. These cells proliferate and differentiate in a suitable 3D culture matrix to form the preliminary structure of an organoid. In this process, the optimization of culture conditions is crucial, including precise control of environmental factors such as temperature, humidity, pH, and oxygen concentration to simulate the in vivo environment and promote cell development and tissue self-assembly.

Culturing organoids requires intricate and specialized techniques in biological research. The fundamental aspect of organoid development involves using 3D culture technology to reproduce the structure and functionality of organs within living organisms. Researchers must choose proper cell sources from stem cells (including pluripotent stem cells and adult stem cells) or specific adult cell types and cultivate these cells while considering the unique features of the target organ. Suitable 3D culture matrices enable these cells to proliferate and differentiate into the basic structure of organoids. Successful cell development and tissue self-assembly depend on optimizing culture conditions through precise environmental factor control like temperature, humidity, pH, and oxygen concentration to create an in vivo-like environment.

Organoids culture includes not only cell selection and 3-D culture set up, but also the addition of specific growth factors and signal molecules that allow the cells to differentiate to give organoids certain function and shape. In the brain organoids culture, for instance, the nervous system can be induced by adding neurodevelopmental factors to pluripotent stem cells; in the liver organoids culture, we need to add hepatocyte growth factors to keep them functional. Moreover, co-culturing immune cells to mimic a microenvironment similar to that of the body could also be employed in the organoid culture to enhance organoids' functionality and stability.

Figure 1 Schematic of the different organoids that can be derived from PSCs.^1,3

Organoids Application

Organoids have wide application prospects in biomedical research, including disease modeling, drug screening, regenerative medicine, precision medicine and other fields.

• Disease modeling: Organoids can be used to simulate the biological processes of a variety of diseases, such as cancer, neurodegenerative diseases, cardiovascular diseases, etc., helping researchers reveal the pathogenesis and development process of diseases, and providing high-throughput for new drug development., high-precision platform.
• Drug screening and precision medicine: By building personalized organoid models of patient origin, researchers can assess the efficacy and safety of drugs on specific patients, thereby guiding the development of personalized treatment plans. In addition, organoids are also used to screen anticancer drugs and test the toxicological properties of drugs.
• Regenerative medicine: Organoid technology shows great potential in tissue repair and organ transplantation. For example, by growing a patient's own stem cells into organoids and transplanting them back into the body, damaged tissue can be repaired or dysfunctional organs can be replaced.
• Basic research: Organoids provide new tools for studying cell differentiation, tissue development, and cell-to-cell interactions. For example, brain organoids can be used to study brain development and neuron maturation processes, while gut organoids can be used to study the interactions of gut microorganisms with their host.

Fig 2 Biomedical applications of cholangiocyte organoids.^2,3

Limitation of organoids

Although organoid technology has shown great potential in simulating the physiological and pathological processes of human organs, it still has the following limitations:

• Complexity limitations: Organoid models can usually only simulate some functions and structures of organs, and it is difficult to completely restore the complexity of real organs, such as the integrity and diversity of multiple cell types and three-dimensional structures.
• Lack of vascularized and immune environment: Most organoids lack vascularized structures, limiting the transport of nutrients and oxygen, affecting long-term survival and function. In addition, the lack of immune cells also prevents organoids from fully simulating the real physiological environment.
• Standardization and repeatability issues: The current preparation and operation methods of organoids lack a unified standardized process, and differences between different laboratories may lead to limited comparability and replicability of results.
• Poor long-term stability: Organoid models usually only maintain activity and function for a limited period of time, and maintaining their long-term stability faces technical challenges.

What are Organ on a chip Models?

Organ-on-a-Chip is a tiny biological organism. On the chip, with multidisciplinary cross-cutting technologies like microfluidics, tissue engineering and microelectronics, a microsystem mimicking the physiological and pathological properties of human organs is assembled. These chips can generate living cells, and mimic human organ function and response through microenvironment management (blood flow, oxygen, nutrients etc). Organ chips alone or bundled into several organ systems can more accurately represent drug metabolic and physiological pathways in the body to make drug research and development more accurate and efficient, to minimise animal testing and give data for disease modeling, new drug discovery, personalized medicine and other applications that have broadly promising applications.

How are the on-chip organ models made?

On-chip organs – organs-on-a-chip – are created by cutting-edge microengineering and cell-culture techniques to replicate human organ function. It all starts with developing microfluidic chips – typically made of polydimethylsiloxane (PDMS) or glass – in which cells are embedded in controlled microenvironments. Such chips consist of tiny chambers and channels resembling the mechanical and structural features of living tissues.

Application of Organ on a chip Models

Drug Development and Toxicity Testing:

• Evaluate the safety and efficacy of new drugs with minimal reliance on animal models.
• Analyze drug absorption, metabolism, and clearance in real-time.
• Reduce the risk of adverse effects in clinical trials.

Disease Modeling:

• Recreate pathological conditions like cancer, cardiovascular diseases, or infections.
• Study disease progression and test therapeutic interventions.

Multi-Organ System Research:

• Simulate interactions between organs, such as the gut-liver or lung-heart axes.
• Enhance understanding of systemic responses and complex inter-organ dynamics.

Personalized Medicine:

• Integrate patient-specific cells into chips for tailored treatments.
• Facilitate precision therapies based on individual biological responses.

Ethical and Human-Relevant Research:

• Provide reliable human-relevant data.
• Reduce ethical concerns by minimizing animal testing.

Limitation of Organ on a chip Models

Organ-on-a-chip models, while highly promising, have several limitations.

• Complexity and Cost. Fabricating and maintaining these models requires advanced microengineering techniques, making them costly and technically challenging. Specialized equipment and expertise are necessary for their development and operation.
• Limited Biological Complexity. While they replicate certain organ functions, current chips lack full biological complexity, such as immune responses or neural integration. The absence of a complete vascular system and complex tissue interactions may limit their physiological accuracy.
• Scalability Issues. Scaling up these models for high-throughput screening or large-scale applications remains difficult. The miniaturized nature of the models restricts the ability to test in large numbers or on a commercial scale.
• Reproducibility. Variability in chip design, cell source, and environmental conditions can lead to inconsistent results, affecting reproducibility. Achieving standardization across different platforms is a challenge.

Key Differences of Organoid vs Organ On A Chip

Integration of Organoids and Organ-on-a-Chip

The integration of organoids and organ chips, or "organoid chip" technology, is a cutting-edge innovation in the field of biomedicine in recent years. It is a highly biomimetic in vitro model. This is an industry with high technical content and multidisciplinary intersection, involving chip design and manufacturing, model construction and functional evaluation, biological research and drug testing, etc.

Organoid chips can significantly improve the reliability of drug efficacy and safety predictions, while reducing costs and drug failure rates, and may provide strong scientific evidence for pre-clinical evaluation and clinical trials of drugs. These characteristics are not available in traditional two-dimensional cell line cultures and animal models, because the data obtained under animal and human, in vitro static and in vivo dynamic conditions are obviously mismatched. Although the OrgOC system is far from faithfully recreating the functions of native human organs, it has shown unique advantages in simulating human physiology and pathology.

Transform Research with Advanced Organ-on-a-Chip Models

At Creative Biolabs, we offer cutting-edge Organ-on-a-Chip (OoC) models to revolutionize your research. Here are 10 of our most advanced solutions, categorized by key research areas:

Disease Modeling

• Alzheimer's Disease-on-a-Chip: Study neurodegenerative diseases with precision.
• COVID-19-on-a-Chip: Investigate respiratory infections and therapeutic strategies.
• Diabetes-on-a-Chip: Explore metabolic disorders and drug efficacy.

Organ-Specific Research

• Liver-on-a-Chip: Ideal for toxicity testing and liver disease studies.
• Brain-on-a-Chip: Perfect for neuroscience and neuroinflammation research.
• Lung-on-a-Chip: Model respiratory diseases like pulmonary fibrosis.

Multi-Organ & Systemic Studies

• Multiple Organs-on-a-Chip: Simulate organ interactions for systemic toxicity and ADME studies.
• Heart-Liver-Cancer Three Organs-on-a-Chip: Study complex organ-drug-cancer interactions.

Custom Solutions

• Customized Organ-on-a-Chip: Tailored models to meet your specific research needs.

Barrier Tissue Research

• Blood-Brain Barrier (BBB)-on-a-Chip: Optimize CNS drug delivery and barrier function studies.

Our OoC platforms integrate microfluidics, 3D cell culture, and real-time monitoring to deliver physiologically relevant data, reducing reliance on animal models and accelerating discovery.

Related Sections:

• What Are Orgnoids
• How to Make Orgnoids
• Organoids vs Traditional Organs
• Spheroids vs. Organoids