Regioselective sulfated chitosan produces a biocompatible and antibacterial wound dressing with low inflammatory response.

The aim of current study is to tailor chitosan derivate which is water-soluble while presents original biological features of chitosan. For this purpose, the 6-O chitosan sulfate (CS) with naked amine groups was synthesized via regioselective modification of chitosan (C) during which both crosslinking capacity and antibacterial properties of the C were remained intact. This was achieved by sulfation the C under controlled acidic conditions using chlorosulfonic acid/sulfuric acid mixture. Subsequently, a chemically crosslinked hydrogel of the CS was used as a wound dressing substrate. The modified sulfate groups retained the biocompatibility of C and showed antibacterial effects against gram-positive and gram-negative bacteria. In addition, the presence of sulfate groups in the CS chemical structure improved its anticoagulant activity compared to the unmodified C. Both in vitro and in vivo enzyme-linked immunosorbent assay (ELISA) measurements showed that CS had a higher potential to bind and scavenger anti-inflammatory cytokines, including IL-6 and transforming growth factor-β (TGF-β), both of which play critical roles in the early stage of the wound healing process. After treatment of full-thickness wounds with CS hydrogels, the macrophage cells (c.a. 6 × 104 cells) expressed significantly more M2 phenotype markers compared to the C group (4.2 × 104 cells). Furthermore, the CS hydrogel induced better re-epithelialization and vascularization of full-thickness wounds in mice compared to the C hydrogel during 30 days.