Tannic acid-loaded chitosan-RGD-alginate scaffolds for wound healing and skin regeneration

Abstract Hydrogels have drawn much attention in the field of tissue regeneration and wound healing owing to the application of biocompatible peptides to tailor structural features necessitating optimal tissue remodeling performance. In the current study, polymers and peptide were explored to develop scaffolds for wound healing and skin tissue regeneration. Alginate (Alg), chitosan (CS), and arginine-glycine-aspartate (RGD) were used to fabricate composite scaffolds crosslinked with tannic acid (TA), which also served as a bioactive. The use of RGD transformed the physicochemical and morphological features of the 3D scaffolds and TA crosslinking of the scaffolds improved their mechanical properties, specifically tensile strength, compressive Young’s modulus, yield strength, and ultimate compressive strength. The incorporation of TA as both a crosslinker and a bioactive allowed for 86% encapsulation efficiency and burst release of 57% of TA in 24 h, accompanied by an 8.5% steady release per day of up to 90% over 5 d. The scaffolds increased mouse embryonic fibroblast cell viability over 3 d, progressing from slightly cytotoxic to non-cytotoxic (cell viability >90%). Wound closure and tissue regeneration evaluations in a SpragueDawley rat wound model at predetermined wound healing time points highlighted the superiority of the Alg-RGD-CS and Alg-RGD-CS-TA scaffolds over the commercial comparator product and control. The scaffolds’ superior performance included accelerated tissue remodeling performance from the early to the late stages of wound healing, indicated by the lack of defects and scarring in scaffold-treated tissues. This promising performance supports the design of wound dressings that can act as delivery systems for the treatment of acute and chronic wounds.