Nanosized Fat Emulsion Injection Modulating Local Microenvironment Promotes Angiogenesis in Chronic Wound Healing

Abstract The current treatment for chronic diabetic wounds is costly for patients and society. The proinflammatory state and impaired vascular condition are the main factors that hamper diabetic wound healing. In this study, fat emulsion (FE), a nanosized product clinically used to provide nutrition and energy to patients through vein injection, is evaluated for its diabetic wound healing capability for the first time. The nanosized FE is mixed with methacrylated hyaluronic acid (HA–MA) hydrogel to form an anti‐inflammatory and angiogenic FE/HA–MA hybrid hydrogel dressing to accelerate the diabetic wound closure. Results of RT‐qPCR analysis and ELISA demonstrate that the FE exerts excellent anti‐inflammatory effects by significantly downregulating the expression of proinflammatory cytokines tumor necrosis factor‐α (TNF‐α) and interleukin‐1β (IL‐1β), both in vitro and in vivo. The endothelial tube formation and scratch assays reveal that the FE promotes angiogenesis and cell migration, respectively, by releasing vascular endothelial growth factor A. The in vivo diabetic wound mouse model confirms an increased blood vessel density, healing rate, tissue epithelialization, and collagen deposition in the FE/HA–MA hybrid hydrogel dressing group compared to the control group. These findings may provide a promising and economic product and strategy for diabetic wound treatment in the clinic.