Glycyrrhizic acid-containing Gastrodia elata polysaccharide/chitosan hydrogel promotes macrophage M2 polarization and accelerates aging skin wound healing.

Abstract

The treatment of senescent wounds has been a hot topic of research, as the presence of chronic inflammation in senescent skin leads to diminished wound healing. While ongoing inflammation also impairs wound healing and leads to complications. As a kind of Chinese herbal medicine with the same source of food and medicine, Gastrodia elata has good biosafety and bioactivity. We discovered that hydrogel systems derived from Gastrodia elata polysaccharide (GEP) exhibit excellent stability and biosafety, suitable for application as a hydrogel dressing for skin wounds. We incorporated glycyrrhizic acid (GLY), an active component, into a GEP-prepared hydrogel. A senescent mouse model was established by in vivo injection of D-galactose. The hydrogel was administered continuously for 21 days after causing dorsal skin injury in mice. The results showed that the hydrogel had good swelling and degradation properties as well as anti-inflammatory, antioxidant and haemostatic activities, which could reduce lipopolysaccharide (LPS)-induced macrophage inflammation and accelerate wound healing by promoting the polarization of macrophages from the M1 phenotype to the M2 phenotype. Further mechanistic studies demonstrated that the glycyrrhizic acid microsphere-loaded hydrogel (GM-Gel) suppresses STAT3 phosphorylation and Bax/Caspase-3 expression, thereby inhibiting M1 polarization. In conclusion, GEP hydrogel is a promising biomaterial for the treatment of chronic wounds as it can significantly promote healing of aging skin wounds by inhibiting macrophage inflammation and accelerating wound repair.