Dynamic hydrogel mechanics in organoid engineering: From matrix design to translational paradigms

Evidence from laboratory and animal studies provides groundwork for understanding mechanisms and potential before human studies continue.

• Level A · Stronger Clinical Evidence
• Level B · Emerging clinical evidence with positive signals
• Level C · Early human research exploring benefits
• Level D · Scientific groundwork from lab and animal studies
• Emerging · Emerging topic under active research

Abstract (original English)

The extracellular matrix (ECM) serves as a dynamic biomechanical regulator of cellular behavior, yet conventional 3D culture systems, such as Matrigel, lack the spatiotemporal control required to dissect mechanotransductive mechanisms in organoids. This review systematically explores the synthesis of mechanically tunable hydrogels-spanning stiffness and viscoelasticity-and their transformative applications in organoid research. By integrating natural, synthetic, and hybrid polymers, these hydrogels enable precise recapitulation of tissue-specific ECM mechanics, overcoming limitations of batch variability and static properties. We categorize hydrogel design strategies, emphasizing crosslinking paradigms (physical vs. chemical) and dynamic bond engineering, which permit real-time modulation of mechanical cues. Applications across developmental organoids (intestinal, hepatic, renal, neural) reveal stiffness-dependent morphogenesis, where optimal mechanical niches enhance maturation via YAP/Notch signaling. Tumor organoid models (breast, pancreatic, colorectal) further demonstrate how matrix stiffening drives malignancy through mechanosensitive pathways, such as epithelial-mesenchymal transition and drug resistance. Emerging viscoelastic hydrogels, tailored via alginate molecular weight or decellularized ECM, replicate dynamic tissue mechanics, advancing cartilage and cerebellar or

Evidence level

Evidence from laboratory and animal studies provides groundwork for understanding mechanisms and potential before human studies continue.

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