Hydrogel innovations for 3D organoid culture

Abstract Organoids are functional cell-tissue complexes that mimic structural and functional characteristics of organs in vitro in three dimensions (3D). Mimicking the natural extracellular matrix (ECM) environment is critical for guiding stem cell fate within organoid cultures. Current organoid cultures predominantly utilize animal- or tumor-derived ECMs such as dECMs and Matrigel. However, these materials introduce batch variability and uncertainty in composition, which hinders reproducibility. In contrast, naturally derived and synthetic hydrogels with excellent biocompatibility offer precise and adjustable compositions, along with tunable mechanical properties, thereby providing robust support for organoid development and maturation. We explore innovative hydrogel designs tailored specifically for organoid cultures, emphasizing the influence and meticulous control of functional hydrogels on organoid formation, differentiation, and maturation processes. Furthermore, the review highlights the potential of functionalized hydrogel scaffolds to advance both research and industrial applications in tissue and organ engineering. As research progresses, investigations will further concentrate on improving the adjustable properties, expanding their scope of application, and more biologically compatible gelation strategies of hydrogels.