Zinc oxide nanoparticles (ZnO NPs) are known for their antibacterial, antioxidant, and anti-inflammatory activities. Moreover, ZnO NPs can stimulate cell migration, re-epithelialization, and angiogenesis. All these attributes are highly relevant to wound healing. Local administration of ZnO NPs to the wound can be achieved through electrospun nanofibers. We hypothesized that the use of poly(lactide-co-glycolic acid) (PLGA)/silk fibroin (SF) nanofiber-based delivery of ZnO would maintain the bioavailability of NPs on the wound area and synchronization with the unique structural features of electrospun nanofibers, could stimulate wound closure, re-epithelialization, collagen deposition, cellular migration, and angiogenesis. In this study, we fabricated PLGA/SF (PS) nanofibrous (NF) membranes with and without ZnO NPs and extensively characterized them for various physicochemical and biological attributes. Scanning electron microscopy (SEM) revealed smooth fibers and ZnO concentration-dependent increase in the fiber diameter. Transmission electron microscopy (TEM) also confirmed the encapsulation of ZnO NPs in the polymer matrix. The successful loading of ZnO was further confirmed by X-ray diffraction. Furthermore, mechanical testing revealed a ZnO concentration-dependent increase in the tensile strength. Moreover, biocompatibility was evaluated through in vitro cell culture. A mild anti-oxidant activity was also noted mainly due to the presence of silk fibroin. In vitro antibacterial tests revealed a ZnO concentration-dependent increase in antibacterial activity and PLGA/SF/3% ZnO (PSZ3) remained completely active against E. coli and S. aureus. More importantly, NF membranes were evaluated for their in vivo wound healing potential. The PSZ3 NF membrane not only facilitated the early wound closure but also remarkably enhanced the quality of wound healing confirmed through histopathological analysis. Re-epithelialization, granulation tissue formation, collagen deposition, and angiogenesis are some of the key parameters significantly boosted by ZnO loaded composite NF membranes. Based on extensive characterization and biological evaluation, the PSZ3 NF membrane has turned out to be a potential candidate for wound healing applications.

Diabetic wounds remain a serious clinical challenge whereas current therapies have limited effects on reducing the high disability and morbidity. Impaired vascularization is closely associated with delayed healing of diabetic wounds and liraglutide (Lira), a GLP-1R receptor agonist, has been reported to promote the angiogenic ability of endothelial cells. However, its application is hindered owing to the unsustainable drug concentration. In this study, we prepared a poly (lactic-co-glycolic acid)/gelatin (PLGA/Gel) nanofibrous mat scaffold to sustain the release of Lira for skin tissue engineering through 1-ethyl-3-(3-dimethylaminopropyl) carbodiimide/N-hydroxy sulfosuccinimide (EDC/NHS), a green cross-linking-graft integration method. The incorporation of Lira into PLGA/Gel increased the pore size, hydrophilicity, elasticity and degradation properties of nanofibrous mats, which were advantageous to wound healing. In addition, the effects on diabetic wound healing, vascularization and its underlying mechanism were evaluated. The results revealed that PLGA/Gel/Lira remarkably improved the healing efficiency of diabetic dermal wounds characterized by shortened wound closure time, increased blood vessel density, and elevated collagen deposition and alignment. In vitro, Lira reversed the inhibitory effects on proliferation, migration, tube differentiation, and VEGF secretion of endothelial cells induced by high glucose (HG). As for the underlying mechanism, Lira specifically decreased the level of miR-29b-3p, targeting the AKT/GSK-3β/β-catenin pathway to regulate the biological function of endothelial cells. In conclusion, for the first time this study combined PLGA/Gel with Lira to take advantage of their synergistic effects to promote vascularization, a promising strategy to accelerate diabetic wound repair.

Aim: In this study, we attempted to regulate the preparation of Alg-CS-Flu three-dimensional scaffolds via a facile freeze-drying method combined with amidation. Materials and methods: Three-dimensional porous flurbiprofen-grafted alginate (Alg)–chitosan (CS) scaffolds were successfully prepared by a facile freeze-drying method combined with amidation for skin tissue engineering applications. Alg-CS composite was first used to load flurbiprofen (Flu), which is a kind of anti-inflammatory non-steroidal molecule. The Flu-loaded Alg/CS composite solution, through freeze-drying and 1-ethyl-3(3-(dimethylamino)propyl) carbodiimide/N-hydroxysuccinimide crosslinking to form an Alg-CS-Flu scaffold, exhibited a uniform and porous morphology that was characterized using scanning electron microscopy. The Alg-CS-Flu as-prepared scaffold was also characterized using Fourier-transform infrared spectroscopy, water contact angle, thermal properties, and stress-strain testing. Results: The results reveal that Flu was successfully grafted onto the surfaces of the Alg-CS-Flu scaffold, which showed good hydrophilicity and appropriate mechanical properties. Furthermore, cell viability, cell morphology from cells cultured in vitro, and hematoxylin-eosin staining after the graft was subcutaneously embedded in mice for 7 d demonstrated that the Alg-CS-Flu scaffold had no unfavorable effects on the adhesion and proliferation of fibroblasts, as well as a good anti-inflammatory property. Conclusion: The developed Alg-CS-Flu scaffold is proposed as a promising material or skin tissue engineering application.