Abstract
Organoid culture systems have emerged as powerful platforms for studying development, disease modeling, and regenerative medicine. However, current models primarily rely on spontaneous self-organization within biomimetic matrices such as Matrigel, which lack precise control over biomechanical cues. Recent advances in mechanobiological engineering highlight the critical role of matrix-derived physical and mechanical properties-such as adhesion presentation, stiffness, viscoelasticity, and geometry-in directing organoid morphogenesis and functional maturation. This review explores how translating in vivo biomechanics into in vitro organoid culture strategies can overcome existing limitations, enhance reproducibility, and enable the development of physiologically relevant organoid systems.