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Organoid systems for mimicking functional replicas of the body organs

Current cellular models are often too simplified for a complex screening test. Many of these models rely on 2D culturing of the cells. However, cells in 2D often do not express the same phenotypic behavior as the natural environment in the body. 2D methods can affect cell-cell and cell-matrix interactions. The most widely 3D models are spheroids that are formed by clusters of cells. In spheroids, cells can interact with each other and the surrounding in 3 dimensions. Although the spheroids facilitate 3D communication for the cells, they have their limitations. For example, most spheroids are made of one cell type that is a barrier for models with higher complexity such as heterogeneous tumors.

An organoid is a 3D cellular structure aimed at mimicking a specific organ. Organoids are stem-cell-derived replicas of organs that are capable of self-organizing and recapitulating the structural and functional characteristics of their matching part in the body. Organoids take benefit from the self-renewal, differentiation, and self-organizing behavior of stem cells to assemble a structure to proxy a target organ that makes them promising for reducing the gap between in vitro and in vivo models.

As the science of organoids grows, more advanced technologies are required for designing, Microfluidic fabrication, maintaining, and functionalizing these systems. Microfluidics is capable of addressing some of the major challenges that organoid research is facing.

Microfluidics technology for organoid research

The design parameters for any system are dictated by the desired application. Organoid produced in microfluidic devices, also called organoid-on-chips might be used for a variety of applications including drug toxicity screening, cancer studies, disease modeling, and developmental research. Depending on the desired application, the complexity of the system can differ.

Organoid systems are simplified in vitro versions of organs in the body. They utilize stem cells to produce realistic and sophisticated anatomy. Therefore, engineering the stem cell niche is of importance. The stem cells are regulated via complex signaling mechanisms including the signals from the surrounding cells, and the ECM as well as the mechanical forces. The physiochemistry of the niche such as the pH and oxygen can also be determinant in stem cell fate. Thus, a desirable organoid on a chip system should allow these items to be controlled. Microfluidic technology is well-known for its capacity for controlling the cell culture using a network of microchannels and microchambers as well as embedded bio/pressure/flow sensors. Microfluidic chips for organoid synthesis are compatible with a wide range of biomaterials and biomimetic scaffolds. The cells and the cell clusters have been introduced to these chips inside an extensive list of hydrogels to mimic the ECM. These microchips provide a dynamic environment for the cell culture as opposed to conventional methods where the cell culture is static. The cells can experience flow forces such as shear stress as well as mechanical forces. The mechanical forces can be simulated by stretching or deforming the membranes while the shear stress and its amount are controlled by the fluid flow over the system.

Additionally, organoid-on-chip systems allow Spatio-temporal control of the culture unit. Also, a network of microfluidic channels can be used as perfusion networks to mimic vascularization and allow transport of the growth factors or construct concentration gradients.

The addition of imaging and sensing modalities to the microfluidic chips removes the need for end-point analysis. Researchers can monitor the status of the organoids at any time during the experiment.

Further Reading

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