Mesh-like Electrospun Membrane Loaded With Atorvastatin Facilitates Cutaneous Wound Healing And Its Mechanism

Objective Functional electrospun membranes are promising dressings for promoting wound healing.However,their microstructure and drug loading capacity need further improvements.It is the first time to design a novel mesh-like electrospun fiber loaded with atorvastatin(ATV)and investigated its effects on paracrine secretion by bone marrow mesenchymal stem cells(BMSCs)and wound healing in-vivo.Methods We fabricated a mesh-like electrospun membrane using a copper mesh receiver.The physical properties of the membranes were evaluated by SEM,FTIR spectroscopy,tensile strength analysis,and contrast angle test.Drug release was measured by plotting concentration as a function of time.We tested the effects of conditioned media(CM)derived from BMSCs on endothelial cell migration and angiogenesis.We used these BMSCs and performed RT-PCR and ELISA to evaluate the expressions of vascular endothelial growth factor(VEGF)and basic fibroblast growth factor(b-FGF)genes and proteins,respectively.The involvement of FAK and AKT mechano-transduction pathways in the regulation of BMSCs secretion by material surface topography was also investigated.Furthermore,we established a rat model of wound healing,applied ATV-loaded mesh-like membranes(Polycaprolactone mesh-like electruspun fibers loaded with atorvastatin,PCL/MAT)seeded with BMSCs on wounds,and assessed their efficacy for promoting wound healing.Results The SEM showed fibers of each membrane were round and continuous.FTIR spectroscopy revealed successful ATV loading in the electrospun fibers.The mechanical tests revealed that the mesh-like structure makes membrane more flexible with better mechanical properties.Compared with random electrospun fibers and mesh-like electrospun fibers without drug load,the PCL/MAT groups induced maximum promotion of human umbilical vein endothelial cell migration.The PCL/MAT promoted angiogenesis and led to the generation of longer tubes than the other treatments.Finally,the PCL/MAT induced maximum gene expression and protein secretion of VEGF and b-FGF.As for material surface topography effect on BMSCs,FAK and AKT signaling pathways were shown to participate in the modulation of BMSCs morphology and its paracrine function.In vivo,PCL/MAT seeded with BMSCs significantly accelerated healing and improved wound area neovascularization and collagen reconstruction in the wound area compared to the other treatments.Conclusion The mesh-like topography of fibrous scaffolds combined with ATV release creates a microenvironment that promotes paracrine secretion in BMSCs,thereby accelerating wound healing.Hence,drug-loaded mesh-like electrospun membranes may be highly efficacious for wound healing and as artificial skin.It is a promising approach to solve the traumatic skin defect and accelerate recovery,which is essential to developing functional materials for future regenerative medicine.