Mesh-like electrospun membrane loaded with atorvastatin facilitates cutaneous wound healing by promoting the paracrine function of mesenchymal stem cells

Abstract

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.

Four‐Arm Polymer‐Guided Formation of Curcumin‐Loaded Flower‐Like Porous Microspheres as Injectable Cell Carriers for Diabetic Wound Healing

“…Tissue engineering combined with MSCs and scaffold materials has attracted significant attention owing to its superior safety and efficacy, which facilitate the repair and regeneration of damaged tissues. [ 54 ] In this study, all mice remained alive without exhibiting any signs of illness or unusual behavior for 21 days after administration. Hepatic and renal function parameters were normal on day 21 in the treatment group and were comparable to those in the control group.…”

Translational Challenges in Drug Therapy and Delivery Systems for Treating Chronic Lower Extremity Wounds

“…Membranes can effectively deliver drugs to wounds under drainage pressure and minimize disruption to the wound bed and drug delivery system by requiring less frequent dressing changes. For example, in a recent study, a mesh-like electrospun membrane delivered atorvastatin and bone marrowderived mesenchymal stem cells (MSCs) to rat wound models to demonstrate the effective use of membranes as an engineered skin substitute drug delivery system [149]. However, films and membranes have limitations in absorbing large volumes of wound exudates, making them unsuitable for highly exuding wounds; for these circumstances, the use of a foam or sponge delivery system may be preferred (Table 2).…”

Recycled Synthetic Polymer-Based Electrospun Membranes for Filtering Applications

“…[20]; fibers can be functionalized before, during, and after spinning [2,21]. Electrospun materials could be used in wide application range such as packaging [22], wound healing [23], tissue engineering [24], drug-releasing systems [25], membranes [26], sensors [27], batteries [28], solar cells [29], supercapacitors [30], catalysts [31], environmental remediation [32], protecting clothing [33], and in many others. Due to all the mentioned advantages, electrospinning is the primary choice for fabricating nanomaterials.…”