Synthetic Matrices for Intestinal Organoid Culture: Implications for Better Performance

Organoids are three-dimensional (3D) self-renewing and self-organizing clusters of cells that imitate an organ's structure and function, making them an important tool in various fields ranging from regenerative medicine to drug discovery. Organoids can be developed ex vivo by isolating adult stem cells from an organ-specific tissue (e.g., intestine, brain, and lung) and allowing the stem cells to grow and differentiate in an appropriate growth media with some structural support elements. A 3D extracellular matrix (ECM) hydrogel, a network of highly hydrophilic cross-linked polymer chains, provides essential support and cues for ex vivo organoid growth. Commercially available hydrogel matrices (for example, Matrigel and collagen) are primarily derived from animal tissues. Notably, these animal-derived hydrogel matrices are not suitable for controlled modifications and pose risks of immunogen and pathogen transfer, thus diminishing their clinical application. These limitations of animal-derived hydrogel matrices can, however, be overcome using synthetic hydrogel matrices based on polymers such as polyethylene glycol, nanocellulose, alginate, hyaluronic acid, and polylactic-co-glycolic acid. This review highlights some of the current approaches and advantages of developing synthetic ECM-mimic hydrogels, focusing primarily on intestinal organoid culture.