A chlorogenic acid-loaded hyaluronic acid-based hydrogel facilitates anti-inflammatory and pro-healing effects for diabetic wounds

The impaired wound healing of diabetic patients is a major healthcare issue worldwide. Current therapeutic strategies usually fail due to the complex biological processes within diabetic wounds such as chronic inflammation, damaged blood vasculature, and immature collagen remodeling. Therefore, emerging treatments are urgently required. Chlorogenic acid (CGA, a phenolic compound found in human dietary products) has demonstrated a number of health-improving properties, including anti-oxidant, anti-inflammatory, antimicrobial, anti-diabetic, and lipid-lowing functions. In this study, the capacity of CGA for promoting diabetic wound healing was assessed using in vitro and ex vivo experimental approaches. Consequently, CGA significantly achieved the anti-inflammatory activity, re-epithelializing effect, and pro-angiogenic function. A hyaluronic acid-based hydrogel (HA, it has been previously developed in our laboratories) was subsequently used in vivo for local administration of CGA to the full-thickness wounds of diabetic mice. The resulting formulation (CGA-HA) significantly improved the healing effects relative to a commercial wound dressing (INTRASITE Gel), which was accompanied with the reduction of inflammation, enhancement of re-epithelialization and angiogenesis, and maturation of collagen remodeling. Our study confirms the potential of CGA-HA in the clinical application for diabetic wound healing.