Sulfated polysaccharide from Gelidium crinale: modulation of angiogenesis and fibrosis in skin repair.

Abstract

Scar tissue formation is a common pathological outcome of skin repair after injury, characterized by excessive collagen deposition and closely associated with inflammation and angiogenesis. This study investigated the effects and related signaling changes of a food-derived sulfated polysaccharide from the red alga Gelidium crinale (GNP) on angiogenesis and scar formation using in vitro and in vivo models. Human umbilical vein endothelial cells (HUVECs) and human keloid fibroblasts (HKFs) were used to evaluate the biological activity of GNP, while an OSA-CMCS self-crosslinking hydrogel was employed as a delivery vehicle to improve local administration in a mouse wound-healing model. GNP significantly inhibited HUVEC migration, invasion, and tube formation, accompanied by reduced expression of angiogenesis-related factors, including PDGF, ANG-II, and HIF-1α, suggesting impaired angiogenic activation. In HKFs, GNP decreased TGF-β1 expression and modulated downstream fibrosis-related signaling, thereby suppressing collagen and fibronectin production. Moreover, incorporation of GNP into the OSA-CMCS hydrogel reduced inflammatory responses, angiogenesis, and collagen deposition in vivo. These findings demonstrate the potential of GNP as a natural anti-scar candidate and provide a promising strategy for the high-value utilization of Gelidium crinale polysaccharides.