Immunomodulatory Activity of Electrospun Polyhydroxyalkanoate Fiber Scaffolds Incorporating Olive Leaf Extract

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 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 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.

Combination of Two Kinds of Medicated Microparticles Based on Hyaluronic Acid or Chitosan for a Wound Healing Spray Patch

“…This interesting observation prompted us to evaluate the opportunity to create a device capable of promoting cell proliferation in the wound site thanks to the presence of HA and simultaneous cell migration thanks to the presence of Cs [11]. Furthermore, the dual function of Cs would favor both cell migration, but also an important antimicrobial action [14,40], the latter strengthened by the OLE [41] which had previously been shown to have anti-inflammatory activity [19]. In Figure 9, it is observed that the MPHA50MPCs50 mixture-medicated or not-has a significantly higher wound healing activity than all the other mixtures tested, probably because the presence of the two components must be balanced to achieve more effective wound healing.…”

“…Olive leaves extract (OLE) preparation was carried out according to the previously reported procedure from Olea europaea var. Olivastra seggianese cultivar [19]. The leaves from which OLE was extracted were collected at CNR-IVALSA, Follonica (GR), Italy.…”

Scaffold-Mediated Immunoengineering as Innovative Strategy for Tendon Regeneration

“…De La Ossa et al, investigated with randomly oriented electrospun polyhydroxyalkanoate (PHA) scaffolds functionalized with OLE, taking into consideration its polyphenols, more concretely oleuropein, as well as luteolin-7-O-glucoside and aspigenin-7-O-glucoside in lower concentrations. These scaffolds were cultured in vitro with human dermal keratinocytes (HaCaT cells) for a period of 24 h. When released by PHA fiber meshes, OLE has been shown to have diverse immunomodulatory effects in vitro, switching from pro-inflammatory to anti-inflammatory environments by downregulating IL-1, IL-6, IL-8 and TNF-α, and even stimulating defensin in the case of polyhydroxybutyrate (PHB)/poly(hydroxyoctanoate-co-hydroxydecanoate) (PHB/PHOHD) scaffolds [ 162 ].…”

Special Features of Polyester-Based Materials for Medical Applications

“…In an attempt to reduce the effects of adverse antibiotics, modern wound dressings loaded with natural antimicrobial agents such as proanthocyanidins (PCAN) extracted from Pelargonium sidoides [ 161 ], Annona leaf extracts [ 164 ], babassu oil [ 19 ], Hypericum perforatum oil (HPO) [ 21 ], melanin [ 18 ], and arginine and chitosan [ 174 ] were developed. Immunomodulatory properties toward skin keratinocytes in vitro were related in the case of olive leaf extract (OLE) incorporation in poly(hydroxybutyrate-co-hydroxyvalerate) (PHBV) and PHB/poly(hydroxyoctanoate-co-hydroxydecanoate) (PHB/PHOHD) nanofibers, due to the antioxidant activity of oleuropein [ 175 ]. An antibacterial and antibiofilm dressing for wound healing was developed based on L-tryptophan and L-phenylalanine-based poly(ester urea)s electrospun fibers, which aimed at delivery of nitric oxide (NO), promoting proliferation, enhancing collagen, and accelerating wound treatment [ 176 , 177 ].…”