_Applied_  
_sciences_  
_Article_  
**Immunomodulatory Activity of Electrospun**  
**Polyhydroxyalkanoate Fiber Scaffolds Incorporating Olive**  
**Leaf Extract**  
**[PERSON] 1,2, [PERSON] 3,4,5, [PERSON] 3,5, [PERSON] 1,6,6, [PERSON] 6,7,8, [PERSON] 3,5, [PERSON] 8, [PERSON] 9, [PERSON] 6,7, [PERSON] 5, [PERSON] 3,4,5, [PERSON] 5,6 and [PERSON] 2,7 \begin{tabular}{p{34.1 pt} p{34.1 pt}}  & Doctoral School in Life Sciences, University of Siena, 53100 Siena, Italy; \\  & [EMAIL_ADDRESS] (J.G.D.I.O.); j.espostiossi@[EMAIL_ADDRESS] (J.E.S.) \\  & 2 Cardiovascular Research Laboratory, Department of Surgical, Medical and Molecular Pathology and Critical Care Medicine, University of Pisa, 56126 Pisa, Italy; [EMAIL_ADDRESS] \\  & 3 Consorzio Interuniversitario Nazionale per la Scienza e Tecnologia dei Materiali (INSTM), 50121 Florence, Italy; [EMAIL_ADDRESS] (A.F.); [EMAIL_ADDRESS] (B.A.); [PERSON].); [EMAIL_ADDRESS] (G.D.) \\  & 4 Department of Experimental Medicine, University of Campania \"[PERSON]\", 80138 Naples, Italy \\  & 5 Department of Civil and Industrial Engineering, University of Pisa, 56122 Pisa, Italy; [EMAIL_ADDRESS] \\  & 6 Department of Pharmacy, University of Pisa, 56126 Pisa, Italy; [EMAIL_ADDRESS] (M.D.); [EMAIL_ADDRESS] (M.M.) \\  & 7 Interdepartmental Research Center \"Nutraceuticalutics and Food for Health\", University of Pisa, 56100 Pisa, Italy \\  & 8 Centre for Textile Science and Engineering, Department of Materials, Textiles and Chemical Engineering, University of Gent, 9000 Gent, Belgium; [PERSON]] \\  & 9 Department of Materials Science \& Engineering, Kroto Research Institute, University of Sheffield, Sheffield S10 2 TG, UK; [EMAIL_ADDRESS] \\  & \multicolumn{1}{p{34.1 pt}}{Correspondence: [EMAIL_ADDRESS]} \\  & & \\ \end{tabular}   
**Featured Application: We produced polyhydroxyalkanoate (PHA) ultrafine fiber meshes incorporating olive leaf extract (OLE), which is rich in polyphenols entitled with antioxidant activity. The unique PHA chemistry, small size and surface topography of electrospun fibers, together with OLE, showed immunomodulatory properties towards skin keratinocytes in vitro. OLE/PHA fiber meshes showed promise for application as tissue engineering dressings in chronic wound repair. **  
**Abstract:** 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 polyhydroxyalkanoate (PHAs), namely, poly(hydroxybutrate-co)hydroxyalerate (PHBW) and polyhydroxybutrate/poly(hydroxyoctanote-co-hydroxycleaned) (PHB/PHOHD), to produce fiber meshes via electrospinning: OLE/PHBW 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 pro-inflammatory 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 antibacterial properties, which is essential in wound healing and tissue regeneration. extraction can be water based, and the electrospinning process usually is performed at room temperature [9; 16; 21; 22; 23]. In this study, after characterization of polyphenol content in OLE, two types of PHA fiber meshes incorporating OLE were produced via electrospinningning and proposed as wound dressings.