Effect of Dual Growth Factor Delivery Using Poly(lactic-co glycolic acid) Mesh on Neovascularization
Skin flaps have the crucial issue that skin necrosis can occur due to tissue ischemia in the distal parts of flaps. To prevent tissue necrosis, skin flaps need to be supplied with sufficient blood perfusion through quick vascularization in the ischemic area. In this study, we fabricated poly(lactic-co-glycolic acid) (PLGA) meshes that had shaped random or alignments using electrospinning and modified the surface of the PLGA mesh, using 3,4-dihydroxy-L-phenylalanine (L-DOPA), for drug delivery. We carried out X-ray photoelectron spectroscopy and contact angle analysis to confirm the L-DOPA coating on the surface of PLGA meshes. Then, we loaded vascular endothelial growth factor (VEGF) and fibroblast growth factor 2 (FGF2) on the PLGA meshes for quicker angiogenesis through synergistic effect of the two growth factors. We investigated whether dual growth factor-loaded PLGA meshes on skin flaps promoted angiogenesis during 7-day treatment. When implanted into ICR mice models for skin flaps, the PLGA random mesh led to a result value of significantly smaller than the PLGA aligned mesh in skin flap necrosis and the epidermal thickness with the PLGA random mesh was much thicker than other groups in the necrotic area. Furthermore, coadministration of the two growth factors with the PLGA random meshes resulted in significantly higher blood vessel density than PLGA aligned mesh by ingrowth of host vessels at the edge of the skin flap. These results indicated that dual growth factor-loaded PLGA meshes could contribute to reducing the necrosis by dual growth factor delivery and geometric cues.
dual growth factor delivery, mouse skin flap, poly(lactic-co-glycolic acid) (PLGA) mesh