Hydrogels containing KYNA promote angiogenesis and inhibit inflammation to improve the survival rate of multi-territory perforator Flaps

Abstract

A new spray adhesive (KYNA-PF127) was established through the combination of thermosensitive hydrogel (Pluronic F127) and KYNA, aimed to investigate the effect of KYNA-PF127 on multi-territory perforator flaps and its possible molecular mechanism. 36 SD male rats with 250-300 g were randomly divided into 3 groups (n = 12): control group, blank glue group and KYNA-PF127 group. KYNA-PF127 hydrogel was prepared and characterized for its morphology and properties using scanning electron microscopy. CCK-8 assay, scratch wound assay, transwell assay, tube formation assay and Ki67 staining were used to study the effect of KYNA-PF127 on the proliferation, migration, and tube formation of HUVECs. VEGF and FGF2 were measured by qPCR to evaluate the angiogenesis capacity of HUVECs in vitro. In vivo, the effect of each group on the survival area of the cross-zone perforator flap was evaluated, and angiogenesis was evaluated by HE and immunofluorescence (CD31 and MMP-9). The effect of inflammation on skin collagen fibers was assessed by Masson. Immunohistochemistry (SOD1, IL-1β, TNF-α) was used to evaluate the effects of oxidative stress and inflammatory factors on multi-territory flaps. KYNA-PF127 has good sustained release and biocompatibility at 25% concentration. KYNA-PF127 promoted the proliferation, migration, and angiogenesis of HUVECs in vitro. In vivo, the survival area of multi-territory perforator flaps and angiogenic capability have increased after KYNA-PF127 intervention. KYNA-PF127 could effectively reduce the oxidative stress and inflammation of multi-territory perforator flaps. KYNA-PF127 promotes angiogenesis through its antioxidant stress and anti-inflammatory effects, and shows potential clinical value in promoting the survival viability and drug delivery of multi-territory perforator flaps.