Dynamic Hydrogels with Tunable Mechanics for 3D Organoid Derivation

The mechanical properties of the hydrogel play a pivotal role in governing the formation and development of 3D organoids in vitro. However, commonly employed natural hydrogels, such as Matrigel and other extracellular matrix (ECM)-derived products, are characterized by ill-defined and complex compositions, resulting in non-tunable mechanical properties. This limitation poses challenges in controlling organoids' developmental trajectory and 3D morphology. Although numerous synthetic hydrogels with well-defined chemical structures have recently been adopted to study organoids by modulating stiffness, advanced research emphasizes the importance of dynamic mechanical cues, such as dynamic stiffness softening and dynamic viscoelasticity, for optimal organoid derivation. These cues are essential for mimicking the dynamic physiological states of organoids during their growth. Despite their potential, the concept of dynamic hydrogels is often used interchangeably, and a systematic review is lacking to clarify this ambiguity. Furthermore, the mechanisms through which dynamic mechanical cues regulate organoid formation have not been thoroughly reported. This review endeavors to summarize and categorize dynamic hydrogels and reveal the effects of dynamic mechanics on organoid derivation. Additionally, the prospects of dynamic hydrogels in organoid derivation are deliberated to promote a more rational design of synthetic hydrogels, guiding organoid derivation and propelling organoid technology in biomedicine.