Immunomodulatory activity of electrospun polyhydroxyalkanoate fiber scaffolds incorporating olive leaf extract

Olive tree is a well-known source of polyphenols. We prepared an olive leaf extract (OLE) and characterized it via high performance liquid chromatography (HPLC) analysis. OLE was blended with different polyhydroxyalkanoates (PHAs), namely, poly(hydroxybutyrate-co-hydroxyvalerate) (PHBHV) and polyhydroxybutyrate/poly(hydroxyoctanoate-co-hydroxydecanoate) (PHB/PHOHD), to produce fiber meshes via electrospinning: OLE/PHBV and OLE/ (PHB/PHOHD), respectively. An 80–90% (w/w%) release of the main polyphenols from the OLE/PHA fibers occurred in 24 h, with a burst release in the first 30 min. OLE and the produced fiber meshes were assayed using human dermal keratinocytes (HaCaT cells) to evaluate the expression of a panel of cytokines involved in the inflammatory process and innate immune response, such as the antimicrobial peptide human beta defensin 2 (HBD-2). Fibers containing OLE were able to decrease the expression of the proinflammatory cytokines at 6 h up to 24 h. All the PHA fibers allowed an early downregulation of the pro-inflammatory cytokines in 6 h, which is suggestive of a strong anti-inflammatory activity exerted by PHA fibers. Differently from pure OLE, PHB/PHOHD fibers (both with and without OLE) upregulated the expression of HBD-2. Our results showed that PHA fiber meshes are suitable in decreasing pro-inflammatory cytokines and the incorporation of OLE may enable indirect antibac-terial properties, which is essential in wound healing and tissue regeneration.