4.5 Article

Electrospun wound dressings containing bioactive natural products: physico-chemical characterization and biological assessment

Journal

BIOMATERIALS RESEARCH
Volume 25, Issue 1, Pages -

Publisher

SPRINGERNATURE
DOI: 10.1186/s40824-021-00223-9

Keywords

Electrospinning; Drug delivery; Nanofibers; Alkannin; Shikonin; Skin tissue engineering; Wound dressings; Wound healing

Funding

  1. project 'MICROMETABOLITE' from the European Union's Horizon 2020 research and innovation programme, under the Marie Sklodowska-Curie grant [721635]
  2. MICROMETABOLITE

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Current research focuses on skin tissue engineering for managing chronic wounds, aiming to develop scaffolds that promote cell growth, offer protection, and deliver drugs. Polymeric nanofibers containing A/S derivatives were fabricated successfully, with CA fiber mats showing favorable properties for cell attachment and migration. A/S ester derivatives and dimeric A/S enhanced cell proliferation, while shikonin and alkannin exhibited toxicity. Alkannin, shikonin, and acetyl-shikonin demonstrated potent antibacterial properties compared to other compounds.
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(epsilon-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 mu M and alkannin only at 1 mu M. 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.

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