Hydrogel nanofiber-based 3D cell cultures and organoids.

Hydrogel-based nano- and microfibers integrate the biomimetic functionality of hydrogels with the topological architecture of fibers, enabling a realistic emulation of the native extracellular matrix for various biomedical applications. Recent advances in nanofiber fabrication and stem cell engineering have positioned nanofibrous hydrogel scaffolds as compelling synthetic alternatives to conventional Matrigel for disease modeling and translational medicine. In this article, we examine hydrogel nanofiber architectures as a distinct class of material-structure systems. We first outline key design methodologies and strategies for modulating mechanical properties and hierarchical scaffold architecture. We then discuss recent studies elucidating how the physicochemical properties of nanofibers regulate mechanotransduction and cellular behaviors, offering a versatile toolbox for advanced in vitro models. By bridging the gap between material synthesis, fabrication, and functional biological maturation, this article provides a roadmap for the development of next-generation translational three-dimensional cell culture platforms.