Critically sized skin flaps used to treat skin defects often suffer from necrosis due to insufficient blood supply. Hence there is an urgent need to improve the survival rate of skin flaps by promoting local angiogenesis. The delivery of growth factor loaded microcarriers have shown promise in enhancing defect repair, however, their rapid clearance from the defect site limits their regenerative potential. Thus, it is critical to develop microcarriers which can promote the sustained release of bioactive factors to effectively stimulate tissue repair. This study aimed to develop a stromal cell-derived factor 1 (SDF-1) loaded microcarrier coated with Matrigel (MC@SDF-1@Mat) to promote skin flap repair. SEM imaging showed that the surface of the microcarrier was coated by a porous Matrigel film. The drug release experiment showed that the Matrigel-coated microcarriers enhanced the sustained release of the model drug methylene blue when compared to uncoated group. MC@SDF-1@Mat significantly promoted the proliferation, migration, and angiogenesis of HUVECs via CCK-8, wound healing assay, and tube formation assay, respectively. Moreover, the murine random skin flap model was further established and treated. It was found that the flap necrosis area in the MC@SDF-1@Mat treated group was significantly reduced. H&E and Masson staining showed the histological structure and collagen organization exhibited a normal phenotype in the MC@SDF-1@Mat treated group. Additionally, CD31 immunohistochemical analysis showed that the MC@SDF-1@Mat treated group exhibited the greatest degree of neovascularization. In conclusion, our SDF-1 functionalized gelatin-based hydrogel microcarrier has potential clinical applications in promoting skin flap repair and drug delivery.
Keywords: SDF-1; drug delivery; microcarrier; skin flap repair; vascularization.