Spatial and Functional Roles of Syndecans in Skin Wound Healing

Wound healing is a complex, multi-phase process involving hemostasis, inflammation, proliferation, and tissue remodeling. Syndecans (SDCs), a family of transmembrane heparan sulfate proteoglycans, serve as co-receptors for growth factors, cytokines, and ECM components, playing critical roles in cell adhesion, migration, proliferation, and angiogenesis. Among them, SDC-1 and SDC-4 are key regulators of skin wound healing. Due to their distinct spatial and temporal expression across various cell types—such as epithelial cells, fibroblasts, and immune cells—SDCs are well-positioned to coordinate regenerative responses. This review focuses on the spatial regulation of SDCs during skin wound healing, highlighting their roles in epidermal and dermal repair, modulation of intracellular signaling, and remodeling of the wound microenvironment. Overall, SDCs are emerging as central modulators of skin wound healing, with promising implications for regenerative medicine in the skin and beyond.