In past studies, cultivating various types of micro-organs has relied on a supportive gel called Matrigel, which forms the 3D scaffolds that allow different types of cells to develop into organoids.
“Matrigel matrix gel is the gold standard for organoid culture, but it has limitations.” First, Matrigel matrix gel is very expensive, and second, it is derived from mouse tumor cells, which won’t work well if you’re considering downstream clinical applications because of its unknown biological components. Additionally, the use of commercially available matrices may introduce biological variability from batch to batch.
Although Matrigel is a relatively widely used substrate for organoid culture, it is not suitable for all types of organoid culture.
(i) Organoid cultures requiring highly controlled environments or precise three-dimensional structures Matrigel, as a natural matrix, provides a suitable growth environment for a wide range of cells, but its composition is complex and difficult to control precisely. For organoids that require precise mimicry of the in vivo microenvironment, such as mimicking tumor microenvironments or complex vascular networks, researchers may prefer to use synthetic matrices with well-defined and adjustable compositions.
(ii) Immune system or nervous system organoids Immune system organoids require precise cell-cell interactions and specific growth factors, which Matrigel may not be able to provide. Nervous system organs, on the other hand, need to mimic neuronal growth and synapse formation, which may require specific extracellular matrix proteins and signaling molecules that may not be adequate in Matrigel.
(iii) High mechanical stress environments Organs such as the heart and liver are subjected to significant mechanical stresses in vivo, such as blood flow impacts. the mechanical properties of Matrigel may not be able to mimic these stresses, and therefore the study of organoids of this type may require the use of synthetic materials with specific stiffness and elasticity.
(iv) Hierarchical structures Tissues such as skin have a hierarchical structure that requires different cell types to interact with each other in specific layers. matrigel may not be able to provide sufficient structural support to maintain this hierarchical structure, and thus more complex culture systems or synthetic matrices may be required to mimic these properties.
(v) Specific Matrix Composition or Physical Properties Organoid tissues, such as bone tissue, that require specific stiffness and composition, cannot be provided with the required physical and chemical properties by Matrigel. Researchers may need synthetic matrices to better mimic the bone tissue environment by adjusting its composition and physical properties.
(vi) Long-term stability and synthetic organoids Degradation of Matrigel may affect the stability of organoids in long-term culture. Synthetic matrices provide long-term stability and controllability for long-term experiments. In addition, the homogeneity and reproducibility of synthetic matrices make them ideal for constructing synthetic organoids.
(vii) Other 1. Animal Origin Issues: Matrigel may not be an appropriate choice for studies seeking to avoid animal-derived materials. The use of human-derived or synthetic materials can avoid potential immune reactions and ethical issues.2. Gene editing or drug screening: Animal-derived proteins in Matrigel may interfere with the delivery of gene editing tools or drug activity. The use of synthetic matrices with well-defined compositions can reduce these interferences and improve the accuracy of experiments.