Background 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-derived 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 mechanotransduction pathways in the regulation of BMSC secretion by material surface topography was also investigated. Furthermore, we established a rat model of wound healing, applied ATV-loaded mesh-like membranes (PCL/MAT) seeded with BMSCs on wounds, and assessed their efficacy for promoting wound healing. Results FTIR spectroscopy revealed successful ATV loading in PCL/MAT. Compared with random electrospun fibers (PCL/R) and mesh-like electrospun fibers without drug load (PCL/M), PCL/MAT induced maximum promotion of human umbilical vein endothelial cell (HUVEC) migration. In the PCL/MAT group, the cell sheet scratches were nearly closed after 24 h. However, the cell sheet scratches remained open in other treatments at the same time point. 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 MSC morphology and its paracrine function. In vivo, PCL/MAT seeded with BMSCs significantly accelerated healing and improved neovascularization and collagen reconstruction in the wound area compared to the other treatments. Conclusions The mesh-like topography of fibrous scaffolds combined with ATV release creates a unique microenvironment that promotes paracrine secretion of 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.
Hemorrhage, infection, and frequent replacement of dressings bring great clinical challenges to wound healing. In this work, Flammulina velutipes extract (FV) and hydroxyethyl cellulose (HEC) were chemically cross-linked and freeze-dried to obtain novel HFV cryogels (named HFVn, with n = 10, 40, or 70 corresponding to the weight percentage of the FV content), which were constructed for wound hemostasis and full-thickness skin defect repair. Systematic characterization experiments were performed to assess the morphology, mechanical properties, hydrophilic properties, and degradation rate of the cryogels. The results indicated that HFV70 showed a loose interconnected-porous structure and exhibited the highest porosity (95%) and water uptake ratio (over 2,500%) with a desirable degradation rate and shape memory properties. In vitro cell culture and hemocompatibility experiments indicated that HFV70 showed improved cytocompatibility and hemocompatibility. It can effectively mimic the extracellular matrix microenvironment and support the adhesion and proliferation of L929 cells, and its hemolysis rate in vitro was less than 5%. Moreover, HFV70 effectively induced tube formation in HUVEC cells in vitro. The results of the bacteriostatic annulus confirmed that HFV70 significantly inhibited the growth of Gram-negative E. coli and Gram-positive S. aureus. In addition, HFV70 showed ideal antioxidant properties, with the DPPH scavenging rate in vitro reaching 74.55%. In vivo rat liver hemostasis experiments confirmed that HFV70 showed rapid and effective hemostasis, with effects comparable to those of commercial gelatin sponges. Furthermore, when applied to the repair of full-thickness skin defects in a rat model, HFV70 significantly promoted tissue regeneration. Histological analysis further confirmed the improved pro-angiogenic and anti-inflammatory activity of HFV70 in vivo. Collectively, our results demonstrated the potential of HFV70 in the treatment of full-thickness skin defects and rapid hemostasis.
Background:The Functional electrospun membrane was a promising strategy to promote wound healing, however, the microstructure and drug loading of the membranes still need further improvement. Here, we designed a novel mesh-like electrospun fibrous loaded with atorvastatin and investigated the effect on the paracrine secretion of BMSCs and wound healing.Methods:We fabricated a mesh-like electrospun membrane by using the copper mesh receiver. Physical properties of the membranes were characterized with Scanning Electron Microscopy, Fourier Transform Infrared Spectroscopy, Tensile Strength Analysis and Contrast Angle Test. The drug Release was measured with a concentration curve of certain times. In vitro, we tested the effect of conditioned-medium (CM) from BMSCs on the migration and pro-angiogenic function of endothelial cells and used the real-time polymerase chain reaction (RT-PCR) to investigate the expression of vascular endothelial growth factor (VEGF) and basic fibroblast growth factor (b-FGF) genes in BMSCs. Furthermore, a wound model of rat was established, the atorvastatin loaded mesh-like membranes (PCL/MAT) seeded with BMSCs were used as artificial skin to evaluate the wound-healing efficiency.Results:The Fourier Transform Infrared Spectroscopy reveals the successful loading of atorvastatin in mesh-like membranes (PCL/MAT). Compared with the random electrospun fibrous (PCL/R) and the mesh-like electruspun fibrous without drug-loading (PCL/M), PCL/MAT has the strongest effect on the migration of HUVECs. The scratches were almost closed after 24h of cell migration in the PCL/MAT group, whereas the scratches maintained a distance for the other groups. The effect of the PCL/MAT group was significant on the pro-angiogenic function of endothelial cells with obviously higher tube length than those of the other groups. And all above corresponding to the increased VEGF and b-FGF gene expression of BMSC in the RT-PCR. In vivo, PCL/MAT seeded with BMSCs significantly accelerated the speed of healing, improved the neovascularization and collagen reconstruction in the wound area compared with the other groups.Conclusions:Mesh-like topography of fibrous scaffolds with atorvastatin releasing can provide unique microenvironment that benefiting paracrine of BMSCs and migration and pro-angiogenic function of endothelial cells, thus accelerating wound healing. It's a novel strategy to design electrospun membranes for wound treatment
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