Liposome/Exosome Hybrid Loaded with FGF2 mRNA for Diabetic Wound Healing.

Diabetic foot ulcer (DFU) is a severe complication of diabetes, characterized by impaired healing due to chronic inflammation, poor blood vessel growth, and compromised cell function. To improve DFU healing, we create a FGF2 mRNA loaded liposome/exosome hybrid (FGF2-LEH) with dual functions of tissue regrowth and inflammation regulation. The FGF2-LEH was fabricated by incubating FGF2 mRNA with liposomes to form the FGF2-Lipo complex, followed by hybridization with platelet-rich plasma-derived exosomes (PRP-Exos) through freeze-thaw cycle and extrusion. Characterizations demonstrated that the FGF2-LEH had suitable particle size, high encapsulation efficiency, and biosafety. In vitro experiments revealed that FGF2-LEH enhanced the migration and tube formation of human umbilical vein endothelial cells, highlighting its pro-angiogenic potential. In both type 1 and type 2 diabetic mouse models, a single dose of FGF2-LEH greatly accelerated wound healing. After 15 days, the healing rate of the FGF2-LEH group exceeded 96% with improved granulation tissue growth, which was superior to that of control. Histopathological analysis further confirmed that FGF2-LEH promoted CD31+ angiogenesis, increased collagen deposition, and induced macrophages toward M2 polarization, thereby improving anti-inflammatory effect. Taken together, FGF2-LEH combining the advantages of PRP-Exos and FGF2 mRNA provides an approach for DFU treatment with translational potential for clinical application.