The novel controlled and localized delivery of drug molecules to target tissues using an external electric stimulus makes electro-responsive drug delivery systems both feasible and desirable, as well as entailing a reduction in the side effects. Novel micro-scaffold matrices were designed based on poly(lactic acid) (PLA) and graphene oxide (GO) via electrospinning. Quercetin (Q), a natural flavonoid, was loaded into the fiber matrices in order to investigate the potential as a model drug for wound dressing applications. The physico-chemical properties, electrical triggering capacity, antimicrobial assay and biocompatibility were also investigated. The newly fabricated PLA/GO/Q scaffolds showed uniform and smooth surface morphologies, without any beads, and with diameters ranging from 1107 nm (10%PLA/0.1GO/Q) to 1243 nm (10%PLA). The in vitro release tests of Q from the scaffolds showed that Q can be released much faster (up to 8640 times) when an appropriate electric field is applied compared to traditional drug-release approaches. For instance, 10 s of electric stimulation is enough to ensure the full delivery of the loaded Q from the 10%PLA/1%GO/Q microfiber scaffold at both 10 Hz and at 50 Hz. The antimicrobial tests showed the inhibition of bacterial film growth. Certainly, these materials could be loaded with more potent agents for anti-cancer, anti-infection, and anti-osteoporotic therapies. The L929 fibroblast cells cultured on these scaffolds were distributed homogeneously on the scaffolds, and the highest viability value of 82.3% was obtained for the 10%PLA/0.5%GO/Q microfiber scaffold. Moreover, the addition of Q in the PLA/GO matrix stimulated the production of IL-6 at 24 h, which could be linked to an acute inflammatory response in the exposed fibroblast cells, as a potential effect of wound healing. As a general conclusion, these results demonstrate the possibility of developing graphene oxide-based supports for the electrically triggered delivery of biological active agents, with the delivery rate being externally controlled in order to ensure personalized release.

Skin diseases are commonly treated with antihistamines, antibiotics, laser therapy, topical medications, local vitamins, or steroids. Since conventional treatments for wound healing (skin allografts, amnion, xenografts, etc.) have disadvantages such as antigenicity of the donor tissue, risk of infection, or lack of basement membrane, skin tissue engineering has become a popular new approach. The current study presents the design and fabrication of a new wound-dressing material by the addition of Juglone (5-hydroxy-1,4-naphthoquinone) to a 25% Polycaprolactone (PCL) scaffold. Juglone (J) is a significant allelochemical found in walnut trees and, in this study is used as a bioactive material. The effects of different amounts of J (1.25, 2.5, 5, 7.5, and 10 mg) on the biocompatibility, mechanical, chemical, thermal, morphological, and antimicrobial properties of the 3D-printed 25% PCL scaffolds were investigated. The addition of J increased the pore diameter of the 25% PCL scaffold. The maximum pore size (290.72 ± 14 µm) was observed for the highest amount of J (10 mg). The biocompatibility tests on the scaffolds demonstrated biocompatible behavior from the first day of incubation, the 25% PCL/7.5 J scaffold having the highest viability value (118%) among all of the J-loaded scaffolds. Drug release of J into phosphate buffered saline (PBS) at pH 7.4 showed that J was completely released from all 25% PCL/J scaffolds within 7 days of incubation.

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Juglone (5-hydroxy-1,4-naphthoquinone) (J) is a naphthoquinone structured allelochemical that is mostly found in the roots, leaves, nut-hulls, bark, and wood of walnut (Juglans regia). In this study, the biocompatibility, mechanical, thermal, chemical, morphological, and antimicrobial properties of the poly(lactic acid) (PLA) (w/v)/J (10, 20, 30 mg) electrospun scaffolds were investigated. Based on the results of the study, it was shown that juglone addition increased the antimicrobial properties of the scaffolds against the Staphylococcus aureus (S. aureus) and Escherichia coli (E. coli), compared to the neat PLA film after 24 h of contact time. According to the tensile test results, the addition of J made the scaffolds more flexible but decreased the mechanical strength. The cytotoxicity properties of the J-added scaffolds demonstrated a toxic behavior on the first day of incubation. However, with an increase in the J ratio, the fibroblast cell metabolic activity increased for all incubation periods.

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