Athanasios S Arampatzis1,2, Konstantinos N Kontogiannopoulos1,2, Konstantinos Theodoridis3,4, Eleni Aggelidou3,4, Angélique Rat5, Anne Willems5, Ioannis Tsivintzelis6, Vassilios P Papageorgiou1,2, Aristeidis Kritis3,4, Andreana N Assimopoulou7,8. 1. Laboratory of Organic Chemistry, School of Chemical Engineering, Aristotle University of Thessaloniki (AUTh), 54124, Thessaloniki, Greece. 2. Natural Products Research Center of Excellence (NatPro-AUTh), Center of Interdisciplinary Research and Innovation of Aristotle University of Thessaloniki (CIRI-AUTh), 57001, Thessaloniki, Greece. 3. Department of Physiology and Pharmacology, Faculty of Health Sciences, School of Medicine, Aristotle University of Thessaloniki (AUTh), 54124, Thessaloniki, Greece. 4. cGMP Regenerative Medicine Facility, Department of Physiology and Pharmacology, Faculty of Health Sciences, School of Medicine, Aristotle University of Thessaloniki (AUTh), 54124, Thessaloniki, Greece. 5. Laboratory of Microbiology, Department of Biochemistry and Microbiology, Faculty of Sciences, Ghent University, 9000, Ghent, Belgium. 6. Physical Chemistry Laboratory, School of Chemical Engineering, Aristotle University of Thessaloniki (AUTh), 54124, Thessaloniki, Greece. 7. Laboratory of Organic Chemistry, School of Chemical Engineering, Aristotle University of Thessaloniki (AUTh), 54124, Thessaloniki, Greece. adreana@cheng.auth.gr. 8. Natural Products Research Center of Excellence (NatPro-AUTh), Center of Interdisciplinary Research and Innovation of Aristotle University of Thessaloniki (CIRI-AUTh), 57001, Thessaloniki, Greece. adreana@cheng.auth.gr.
Abstract
BACKGROUND: Current research on skin tissue engineering has been focusing on novel therapies for the effective management of chronic wounds. A critical aspect is to develop matrices that promote growth and uniform distribution of cells across the wound area, and at the same time offer protection, as well as deliver drugs that help wound healing and tissue regeneration. In this context, we aimed at developing electrospun scaffolds that could serve as carriers for the bioactive natural products alkannin and shikonin (A/S). METHODS: A series of polymeric nanofibers composed of cellulose acetate (CA) or poly(ε-caprolactone) (PCL) and varying ratios of a mixture of A/S derivatives, has been successfully fabricated and their physico-chemical and biological properties have been explored. RESULTS: Scanning electron microscopy revealed a uniform and bead-free morphology for CA scaffolds, while for PCL beads along the fibers were observed. The average diameters for all nanofibers ranged between 361 ± 47 and 487 ± 88 nm. During the assessment of physicochemical characteristics, CA fiber mats exhibited a more favored profile, while the assessment of the biological properties of the scaffolds showed that CA samples containing A/S mixture up to 1 wt.% achieved to facilitate attachment, survival and migration of Hs27 fibroblasts. With respect to the antimicrobial properties of the scaffolds, higher drug-loaded (1 and 5 wt.%) samples succeeded in inhibiting the growth of Staphylococcus epidermidis and S. aureus around the edges of the fiber mats. Finally, carrying out a structure-activity relationship study regarding the biological activities (fibroblast toxicity/proliferation and antibacterial activity) of pure A/S compounds - present in the A/S mixture - we concluded that A/S ester derivatives and the dimeric A/S augmented cell proliferation after 3 days, whereas shikonin proved to be toxic at 500 nM and 1 μM and alkannin only at 1 μM. Additionally, alkannin, shikonin and acetyl-shikonin showed more pronounced antibacterial properties than the other esters, the dimeric derivative and the A/S mixture itself. CONCLUSIONS: Taken together, these findings indicate that embedding A/S derivatives into CA nanofibers might be an advantageous drug delivery system that could also serve as a potential candidate for biomedical applications in the field of skin tissue engineering.
BACKGROUND: Current research on skin tissue engineering has been focusing on novel therapies for the effective management of chronic wounds. A critical aspect is to develop matrices that promote growth and uniform distribution of cells across the wound area, and at the same time offer protection, as well as deliver drugs that help wound healing and tissue regeneration. In this context, we aimed at developing electrospun scaffolds that could serve as carriers for the bioactive natural products alkannin and shikonin (A/S). METHODS:A series of polymeric nanofibers composed of cellulose acetate (CA) or poly(ε-caprolactone) (PCL) and varying ratios of a mixture of A/S derivatives, has been successfully fabricated and their physico-chemical and biological properties have been explored. RESULTS: Scanning electron microscopy revealed a uniform and bead-free morphology for CA scaffolds, while for PCL beads along the fibers were observed. The average diameters for all nanofibers ranged between 361 ± 47 and 487 ± 88 nm. During the assessment of physicochemical characteristics, CA fiber mats exhibited a more favored profile, while the assessment of the biological properties of the scaffolds showed that CA samples containing A/S mixture up to 1 wt.% achieved to facilitate attachment, survival and migration of Hs27 fibroblasts. With respect to the antimicrobial properties of the scaffolds, higher drug-loaded (1 and 5 wt.%) samples succeeded in inhibiting the growth of Staphylococcus epidermidis and S. aureus around the edges of the fiber mats. Finally, carrying out a structure-activity relationship study regarding the biological activities (fibroblast toxicity/proliferation and antibacterial activity) of pure A/S compounds - present in the A/S mixture - we concluded that A/Sester derivatives and the dimeric A/S augmented cell proliferation after 3 days, whereas shikonin proved to be toxic at 500 nM and 1 μM and alkannin only at 1 μM. Additionally, alkannin, shikonin and acetyl-shikonin showed more pronounced antibacterial properties than the other esters, the dimeric derivative and the A/S mixture itself. CONCLUSIONS: Taken together, these findings indicate that embedding A/S derivatives into CA nanofibers might be an advantageous drug delivery system that could also serve as a potential candidate for biomedical applications in the field of skin tissue engineering.
Authors: Athanasios S Arampatzis; Olga Tsave; Benjamin Kirchweger; Julia Zwirchmayr; Vassilios P Papageorgiou; Judith M Rollinger; Andreana N Assimopoulou Journal: Front Pharmacol Date: 2022-06-08 Impact factor: 5.988