Electrically Triggered Drug Delivery from Novel Electrospun Poly(Lactic Acid)/Graphene Oxide/Quercetin Fibrous Scaffolds for Wound Dressing Applications
Alexa-Maria Croitoru,
Yasin Karaçelebi,
Elif Saatcioglu,
Eray Altan,
Songul Ulag,
Huseyin Kıvanc Aydoğan,
Ali Sahin,
Ludmila Motelica,
Ovidiu Oprea,
Bianca-Maria Tihauan,
Roxana-Cristina Popescu,
Diana Savu,
Roxana Trusca,
Denisa Ficai,
Oguzhan Gunduz,
Anton Ficai
Affiliations
Alexa-Maria Croitoru
Department of Science and Engineering of Oxide Materials and Nanomaterials, Faculty of Applied Chemistry and Materials Science, University Politehnica of Bucharest, Gh. Polizu St. 1-7, 060042 Bucharest, Romania
Yasin Karaçelebi
Center for Nanotechnology & Biomaterials Application and Research (NBUAM), Department of Bioengineering, Faculty of Engineering, Marmara University, 34722 Istanbul, Turkey
Elif Saatcioglu
Center for Nanotechnology & Biomaterials Application and Research (NBUAM), Department of Metallurgical and Materials Engineering, Faculty of Technology, Marmara University, 34722 Istanbul, Turkey
Eray Altan
Center for Nanotechnology & Biomaterials Application and Research (NBUAM), Department of Metallurgical and Materials Engineering, Faculty of Technology, Marmara University, 34722 Istanbul, Turkey
Songul Ulag
Center for Nanotechnology & Biomaterials Application and Research (NBUAM), Department of Metallurgical and Materials Engineering, Institute of Pure and Applied Sciences, Marmara University, 34722 Istanbul, Turkey
Huseyin Kıvanc Aydoğan
Department of Electrical and Electronics Engineering, Faculty of Engineering, Marmara University, 34722 Istanbul, Turkey
Ali Sahin
Genetic and Metabolic Diseases Research and Investigation Center, Department of Biochemistry, Faculty of Medicine, Marmara University, 34722 Istanbul, Turkey
Ludmila Motelica
Department of Science and Engineering of Oxide Materials and Nanomaterials, Faculty of Applied Chemistry and Materials Science, University Politehnica of Bucharest, Gh. Polizu St. 1-7, 060042 Bucharest, Romania
Ovidiu Oprea
Department of Science and Engineering of Oxide Materials and Nanomaterials, Faculty of Applied Chemistry and Materials Science, University Politehnica of Bucharest, Gh. Polizu St. 1-7, 060042 Bucharest, Romania
Bianca-Maria Tihauan
Research and Development Department, The National Institute for Research & Development in Food Bioresources, Dinu Vintila St. 6, 021102 Bucharest, Romania
Roxana-Cristina Popescu
“Horia Hulubei” National Institute for Research & Development in Physics and Nuclear Engineering, Reactorului, No. 30, 077125 Magurele, Romania
Diana Savu
“Horia Hulubei” National Institute for Research & Development in Physics and Nuclear Engineering, Reactorului, No. 30, 077125 Magurele, Romania
Roxana Trusca
Department of Science and Engineering of Oxide Materials and Nanomaterials, Faculty of Applied Chemistry and Materials Science, University Politehnica of Bucharest, Gh. Polizu St. 1-7, 060042 Bucharest, Romania
Denisa Ficai
Department of Science and Engineering of Oxide Materials and Nanomaterials, Faculty of Applied Chemistry and Materials Science, University Politehnica of Bucharest, Gh. Polizu St. 1-7, 060042 Bucharest, Romania
Oguzhan Gunduz
Center for Nanotechnology & Biomaterials Application and Research (NBUAM), Department of Metallurgical and Materials Engineering, Faculty of Technology, Marmara University, 34722 Istanbul, Turkey
Anton Ficai
Department of Science and Engineering of Oxide Materials and Nanomaterials, Faculty of Applied Chemistry and Materials Science, University Politehnica of Bucharest, Gh. Polizu St. 1-7, 060042 Bucharest, Romania
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.
