Research Progress on Functional Hydrogels for Regulating Stem Cell Fate and Tissue Regeneration

Functional hydrogels provide hydrated, tunable, and biomimetic matrices for regulating stem cell behavior during tissue regeneration. Their physicochemical properties can be designed to approximate native extracellular matrices, including stiffness, viscoelasticity, degradability, porosity, adhesive ligand presentation, growth factor retention, ionic conductivity, and responsiveness to biochemical or physical stimuli. Recent studies have shifted hydrogel design from passive cell delivery toward dynamic regulation of stem cell fate, endogenous cell recruitment, paracrine signaling, immune modulation, and tissue-specific remodeling. Hydrogel-mediated control of stem cells is mainly achieved through integrin-dependent adhesion, cytoskeletal tension, YAP/TAZ and focal adhesion signaling, lineage-specific morphogen delivery, extracellular vesicle retention, macrophage polarization, angiogenesis, and matrix remodeling. These mechanisms are increasingly applied in bone, cartilage, intervertebral disc, neural, cardiovascular, cutaneous, corneal, and reproductive tissue repair. This review summarizes recent progress in the construction of functional hydrogels, microenvironmental biomimicry, molecular regulation of stem cell fate, and tissue regeneration applications. The discussion emphasizes evidence from 2021 to 2026 and focuses on design principles that connect material properties with stem cell responses and regenerative outcomes.