Recent advances in fucoidan for stem cell protection and regenerative tissue repair.

Fucoidan, a structurally heterogeneous family of sulfated fucose-rich polysaccharides predominantly sourced from brown seaweeds, has emerged as a compelling bioactive macromolecule in regenerative medicine owing to its anti-inflammatory, antioxidant, and pro-survival properties toward stem and progenitor cells. Fucoidan's sulfated backbone imparts a strong negative charge, enabling interactions with growth factors, cell receptors, and extracellular matrix proteins. This modulates key signalling pathways (PI3K/Akt, MAPK, Nrf2/HIF-1α, NF-κB), regulating stem cell survival, proliferation, and differentiation under stress. Advances in macromolecular design have enabled the integration of fucoidan into injectable hydrogels, three-dimensional scaffolds, nanoparticle systems, and liposomal carriers that replicate extracellular matrix function and support controlled delivery of angiogenic and neurotrophic factors. These constructs promote neuroprotection and axon regeneration in spinal cord injury, enhance pro-angiogenic stem cell recruitment in ischemia, support bone and cartilage formation via mesenchymal stem cell differentiation, and accelerate wound healing. Despite these advances, clinical translation is limited by source-dependent variability, a lack of standardized characterization, poor oral bioavailability, issues with dose optimization, and unclear regulatory pathways. This review links fucoidan's chemistry to its stem cell-mediated regenerative effects, surveys biomaterial applications across four tissues, assesses translational barriers, and proposes a structure-guided roadmap for clinically viable designs.