Home / microfluidic reviews / Organs-on-chip & 3d cell culture / Organoids VS Organ-on-a-chip: A Comparative Review of Advanced In Vitro Models
Microfluidic reviews

ORGANOIDS VS ORGAN-ON-A-CHIP: A Comparative Review of Advanced In Vitro Models

Organoids vs organ on chip comparaison image

The advancement of in vitro models has reshaped the landscape of biomedical research, providing unprecedented opportunities for simulating human organ functions. Microphysiological systems (MPS), encompassing organoids and organ-on-a-chip (OoC) technologies, are redefining how we study human biology. These systems represent a significant step forward from traditional 2D cell cultures by extending the life span of cell cultures and adding physiological complexity. MPS models are particularly impactful in cancer research, enabling long-term pharmacokinetic and pharmacodynamic evaluations. Both of which are reshaping how we study diseases, test drugs, and explore the intricacies of human biology. However, these two systems differ significantly in how they replicate organ structures, their applications, limitations, and future prospects.

What Are Organoids?

Organoids are miniature, three-dimensional cellular structures that closely mimic the architecture and functionality of human organs. The development of organoids dates back to 2009, when Hans Clevers’ research team demonstrated that a single LGR5+ intestinal stem cell could differentiate and form an entire crypt-villus structure in a 3D culture environment. This was achieved by embedding cells in Matrigel and culturing them with specific growth factors, such as R-spondin 1 (a WNT agonist), epidermal growth factor (EGF), and bone morphogenetic protein (BMP) inhibitors. Today, organoid models have been established from nearly every major human tissue, including the brain, lung, liver, pancreas, and kidneys

How Organoids Are Cultured

Organoid development relies on the self-organizing capacity of stem cells, either adult stem cells or induced pluripotent stem cells (iPSCs). Notably, iPSCs offer higher cellular diversity, making them advantageous for creating complex tissue models. These stem cells are grown in a gel-like matrix, often Matrigel, which mimics the extracellular matrix and provides structural support. Non-adherent microwell plates and hanging drop cultures are also used to facilitate 3D growth. The organoid culture environment requires specific media formulations tailored to the organ type, often involving multiple growth factors and signaling inhibitors to help cells differentiate. This intricate setup allows the organoid to develop tissue-specific features, such as epithelial layers, glandular structures, and neuronal networks.

organoids culture methods

Applications of Organoids

 

The versatility of organoids has opened new avenues for research in several areas:

  • Cancer Biology: Tumor organoids retain the genetic and histological features of the original tumors, enabling researchers to explore tumor heterogeneity, drug resistance mechanisms, and the tumor microenvironment.
  • Regenerative Medicine: Organoids are being studied for their potential to be grafted into patients with organ failure or scarred tissue, offering new possibilities for tissue repair and organ replacement.
  • Infectious Diseases: Organoids have been used to model infections, such as Zika virus in brain organoids, providing insights into disease mechanisms.
  • Personalized Medicine: Derived from a patient’s own cells, organoids can offer insights into individual drug responses, paving the way for tailored treatment approaches.
  • Developmental Biology: Organoids mimic organogenesis, helping researchers study the complex processes of human development.

 Adapted image from Long-Term Culture of Genome-Stable Bipotent Stem Cells from Adult Human Liver, Meritxell Hutch et al., 10.1016/j.cell.2014.11.050

Limitations of Organoids

Despite their advantages, organoids face several limitations:

  • Lack of Key Systems: Organoids typically lack immune, nervous, and circulatory systems, making it difficult to study complex interactions between different physiological systems.
  • Necrotic Core Formation: Interior cells can receive insufficient nutrients and oxygen due to a lack of vascularization, leading to the formation of necrotic cores.
  • Reliance on Gel Compositions: Organoids often use gels like Matrigel, which offer limited environmental control and result in batch-to-batch variability, reducing reproducibility.
  • Genetic Drift: Maintaining organoids in culture can be challenging, as genetic drift may occur over time, altering the cell population.
  • Specialized Media Requirements: Organoids require tissue-specific media formulations, adding to the complexity and cost of maintaining these cultures.

What Are Organ-on-a-Chip?

Organ-on-a-chip (OoC) technology represents a more engineered approach to replicating organ functions by using microfluidic devices designed to simulate tissue-tissue interfaces, mechanical forces, and chemical gradients found in human organs. These devices house different cell types in synergy, mimicking the complex interplay present in living tissues. 

organ on chip inforgraphic key advantages

Typically made from optically transparent materials like polydimethylsiloxane (PDMS), OoC systems feature microchannels lined with living cells, often separated by semipermeable membranes or embedded in extracellular matrix (ECM) gels, with a controlled microfluidic system. This setup enables the efficient transport of nutrients and waste, provides mechanical stimuli, and allows for precise management of the microenvironment and establishing chemical gradients. Originating from advances in microfluidics and tissue engineering, OoC technology offers more physiologically relevant in vitro models compared to traditional 2D cell cultures or static 3D organoids.

interested in perfoming organ-on-a-chip?

Discover our Microfluidic flow control & chip solutions for organ-on-a-chip experiments

How Organ-on-a-Chip Systems Are Fabricated

The fabrication of organ-on-a-chip devices often involves techniques like soft lithography, which requires clean room facilities and specialized equipment to mold intricate microfluidic channels. Researchers are also exploring alternative fabrication methods, such as 3D printing, laser cutting, and adhesive layer stacking. Once fabricated, the chips are connected to external reservoirs, pumps, and tubing, creating a dynamic flow system that supplies fresh media and removes waste. This setup replicates physiological processes like the rhythmic contractions of heart tissue, alveolar gas exchange in the lung, and kidney filtration.

Applications of Organ-on-a-Chip

Organ-on-a-Chip (OoC) systems are at the cutting edge of drug development and precision medicine:

  • High-Throughput Drug Screening: By mimicking human organ functions, OoC systems allow for efficient drug screening and the assessment of drug efficacy and toxicity in a controlled environment.
  • Disease Modeling: Lung-on-a-chip devices have been used to model pulmonary diseases and test the safety of inhaled therapeutics.
  • Hepatotoxicity Testing: Liver-on-a-chip models are particularly valuable for evaluating the toxic effects of drugs on liver function.
  • Multi-Organ Systems: “Body-on-a-chip” platforms simulate organ-organ interactions, providing a comprehensive view of systemic drug effects and human physiology.
  • Reduction of Animal Testing: These systems offer a more ethical and accurate approach to preclinical research, significantly reducing the reliance on animal models.

Perform your tailored PDMS chip

A complete kit for PDMS chip fabrication

Limitations of Organ-on-a-Chip

While organ-on-a-chip technology provides dynamic and physiologically relevant models, it comes with several challenges:

  • Complexity and Maintenance: These systems require careful design and precise operation, often involving extensive setup and ongoing maintenance.
  • Resource Limitations: Many laboratories do not have access to the resources needed for soft lithography and microfabrication, prompting the exploration of alternative methods such as laser cutting, adhesive film stacking, and 3D printing.
  • Contamination Risks: Connecting microfluidic devices to pumps and tubing increases the risk of contamination, which can jeopardize the experiment.
  • Bubble Formation: Bubbles in the microchannels can obstruct media flow, compromising cell viability and affecting experimental outcomes.
  • Fabrication and Scalability: Producing consistent and reproducible chips is labor-intensive and costly, making scalability for industrial use a significant challenge.
  • Standardization and Regulatory Approval: Standardizing these systems and achieving regulatory approval are major hurdles that must be overcome for widespread adoption.

Future Perspectives and Integration Potential

The future of in vitro modeling lies in integrating organoids with organ-on-a-chip technology, paving the way for advancements in personalized medicine and pharmacogenomics. These hybrid models could enable more accurate disease modeling, drug screening, and the development of targeted therapies using patient-derived cells. However, the field still faces challenges and need to focus on common perspectives:
  • Material Research Advancements: Developing new culture media, ECM-mimicking hydrogels, and advanced materials is essential for creating physiologically accurate in vitro models. These materials provide the necessary structural and biochemical cues for proper cell differentiation and function.
  • Deep Learning and Artificial Intelligence: Leveraging computer vision and automated image analysis can accelerate research and improve reproducibility. These technologies help interpret complex datasets, addressing time-consuming aspects and enhancing the effectiveness of organ-on-a-chip systems.
  • Global Collaboration and Standardization: Collaborative international efforts can reduce costs, increase accessibility, and drive the standardization needed for clinical and commercial applications. Establishing validation criteria and regulatory frameworks is crucial for the successful translation of these technologies.

Organoids-on-a-Chip: Bridging the Gap

The concept of Organoids-on-a-chip represents a groundbreaking approach to overcoming the limitations of traditional organoids and organ-on-a-chip systems. By integrating organoids into microfluidic platforms, researchers can provide a more physiologically relevant microenvironment with controlled perfusion, mechanical stimuli, and biochemical gradients. This integration allows for better modeling of organ-specific functions, such as vascularized tissues, and facilitates the study of organ-organ interactions in a dynamic setting. Organoids-on-a-chip platforms are poised to transform drug testing and disease research by offering higher reproducibility, enhanced scalability, and the ability to capture complex physiological processes. The development of these hybrid systems could mark a significant step forward in creating in vitro models that closely mimic human organs, bringing us closer to personalized and precision medicine.

organoids on chip
Adapted image from: Human organoids-on-chips for biomedical research and applications, Hui Wang et al. Theranostics, 10.7150/thno.90492

Conclusion

Organoids and organ-on-a-chip systems represent complementary approaches to advancing biomedical research. Organoids excel in capturing the genetic and histological features of human tissues, making them ideal for personalized medicine and cancer research. In contrast, organ-on-a-chip devices provide a dynamic, perfused environment that mimics organ functions, offering insights into drug efficacy and toxicity. By addressing the limitations of each technology and exploring their integration, researchers can unlock new possibilities for understanding human biology and developing more effective therapies. A concerted effort toward standardization is essential for maximizing the potential of these technologies, ultimately paving the way for a future where personalized and precision medicine becomes the norm.

Modular Microfluidic range

Designed to be flexible and scalable, ideal for both Research and Development.
References
More about microfluidics
Check our premium instruments range
Get the latest microfluidics news


    I hereby agree than Elveflow uses my personal data

    Contact
    How can we help you?
    Quoteor technical request Job application Job
    application
    Collaboration or partnerships Collaborations
    or partnerships
    Customer support Customer
    support
    Others questions Other

      Get a quote




      We will answer within 24 hours

      By filling in your info you accept that we use your data.

      Contacting for
      a job application?
      We are happy that you are interested in Elveflow. You can apply to our open jobs or send us your open application on WelcomeToTheJungle. Over here!

        Collaborations




        We will answer within 24 hours

        By filling in your info you accept that we use your data.

          Need customer support?







          I hereby agree that Elveflow uses my personal data

          We will answer within 24 hours

            How can we help you?




            We will answer within 24 hours

            By filling in your info you accept that we use your data.