Sulfated Polysaccharides in Wound Healing: From Bioactive Materials Design to Regenerative Therapeutics

Sulfated polysaccharides (SPs) are emerging as a versatile class of bioactive macromolecules for wound healing, owing to their intrinsic roles in cell signaling, immunomodulation, tissue repair, and host defense. As wound healing is a dynamic and tightly coordinated process, particularly in chronic and refractory wounds, a central question is how SP-based biomaterials can be engineered to modulate the wound microenvironment with spatiotemporal precision. Natural and engineered SPs offer distinct advantages, including structural diversity, inherent bioactivity, and tunable physicochemical properties. Mechanistically, SPs regulate key aspects of repair through macrophage polarization, sequestration and presentation of heparin-binding proteins and growth factors, antimicrobial activity, and extracellular matrix (ECM) remodeling. Recent advances have enabled SP-based platforms in the form of hydrogels, microneedles, microspheres, and nanofibrous scaffolds, which provide biochemical and mechanical cues to orchestrate inflammation resolution, angiogenesis, infection control, and tissue regeneration. This Review outlines the sources, structural features, and engineering strategies of SPs, highlights the transition from natural to engineered systems, and discusses recent progress and translational challenges in SP-based wound therapeutics.