Green synthesis of chitosan sulfate using deep eutectic solvent and its application in wound healing

The biomedical potential of chitosan (CS) in wound healing is constrained by poor solubility and processability. Herein, we report a green and efficient route to synthesize water-soluble sulfated chitosan (SCS) with controlled sulfation patterns, using a sulfamic acid-urea deep eutectic solvent (DES). Comprehensive characterization (FTIR, ¹³C and HSQC NMR, HPSEC-MALLS-RI, and elemental analysis) verified tunable sulfation and molecular weights, with zeta potential further delineating the corresponding surface properties. Biological evaluations demonstrated that SCS possesses excellent biocompatibility, promotes cell migration, enhances TGF-β1/VEGF secretion, and facilitates angiogenesis, collagen deposition, and extracellular matrix remodeling. Structure-activity analysis revealed sulfation patterns determined bioactivity, with 6-O-sulfated SCS demonstrating superior wound closure rates (96.2% in 6-O-SCS vs. 88.6% in control group on 12 day post-treatment). This study provides a sustainable approach to SCS production and highlights its therapeutic potential in wound management.