Functionalized Carboxymethyl Chitosan Derivatives in Wound Healing

Wound healing biomaterials need to reduce inflammation, deliver growth factors, inhibit microorganisms, and perform gas-permeable wound dressings. In these respects, carboxymethyl chitosan (CMCS) and its derivatives present numerous advantages as they are naturally antibacterial and have anti-inflammatory properties, and are cytocompatible with fibroblasts and keratinocytes of skin tissue. However, CMCS materials were used in carefully designed physical forms and formulations with other macromolecules and bioactive molecules because of the versatility of skin defects and the complexity of chronic wound therapies. Adhesive gel forms of CMCS-based materials showed promising results as they would adhere and cover the wound surface tightly. In addition, they help in tissue regeneration by fast biodegradation that matches the wound healing process. In preparation of CMCS-based adhesives, carboxyl-activated carbodiimide crosslinkers, and aldehyde-oxidized polysaccharides, like dextran and alginate, were successfully used. Self-healing hydrogels are a new type of wound dressing material that was prepared with Schiff base and disulfide functionalized oligomers and polymers that can make reversible covalent bonds with CMCS chains. Due to their scavenging of ROS species, anti-inflammatory properties, and therefore, increasing wound regeneration, bioactive ingredients of traditional medicine were combined with CMCS hydrogels and hence showed promising results. However, direct wound healing was achievable by careful and timely delivery of growth factors (e.g., EGF, FGF, and VEGF) within the CMCS gel matrix, and often required the use of micro- and nanoparticles-based delivery systems. Lastly, the blending of CMCS with different macromolecules was the most studied topic as the literature survey showed. Composites of CMCS improved the mechanical performances of wound dressing materials and attributed multiple functions including antimicrobial, antioxidative, angiogenic, and wound regenerating properties.