## 4 Discussion  
Chronic wounds result from a widespread group of pathologies, including, among others, ulcers from diabetic, vascular and pressure diseases [28]. Such wounds still represent a healthcare challenge around the globe by affecting several millions of people, as they remain unhaeled for months or years. Even if the underlying pathologies play a key role in wound establishment and perpetuation, chronic wounds possess some common features, defined as \"_prolonged or excessive inflammation, persistent infections, formation of drug-resistant microbial biofilms, and the inability of dermal and/or epidermal cells to respond to reparative stimuli_\" [28]. The possibility of modulating the inflammatory processes and improving the self-defense towards microorganisms can thus facilitate a more efficient regeneration operated by skin cells. Dressings are usually applied at the wound site to enable protection, homeostasis and absorb exudate if needed [29]. The modern wound dressings also aim to facilitate the reparatory processes by releasing growth factors or providing material-intrinsic antimicrobial properties [30]. Bioresorbable natural-origin materials offer remarkable opportunities in this field; in fact, if these biomaterials are spun into micrometric or submicrometric fibers, a structure similar to the fibrous components of ECM is provided for the neighboring cells to repair a wound [16]. To this purpose, biomaterial scaffolds stimulating immunomodulatory and antimicrobial activity in the skin cells, would offer a relevant alternative to current treatments. We hypothesized that the polyphenols present in OLE could provide a beneficial role in skin immunomodulation and that their presence in a fibrous dressing could promote their function by means of a better controlled local release to the cells within/from a three-dimensional (3D) structure. We considered a novel family of polyesters, i.e., PHAs, as a bio-based polymer source to produce ultrafine fiber nonwovens via electrospinningning. Previous studies with plain PHAs confirmed the good electro-spinability of these polymers [31; 32; 33]. In this study, by using identical solvents and solution parameters, two types of fiber mesh were obtained: one based on commercial PHBIV and one based on a blend of two laboratory-produced PHAs, i.e., PHB/PHOHD, which were previously tested under distinct electrospinningning modalities and apparatus [31; 32; 33]. Both of them were loaded with the same amount of OLE and used for in vitro tests performed using human dermal keratinocytes (HaCaT cells). We observed that the presence of OLE differently affected the final architecture of two PHA formulations, by favoring the formation of beads and molten fibers in particular in the PHB/PHOHD nonwovens. In electrospun manufacts, beads are considered as morphological defects due to nonoptimal electrospinningning conditions, as the fiber diameter is not consistent along fiber length [34]. Beads result to strongly depend on surface tension, and solvents or additives can help to reduce this phenomenon [35]. However, it has been reported that in case of fibrous meshes loaded with bioactive agents, beaded structures can act as mini-reservoirs of the drug, thus enabling a better tunable delivery [36]. Similar to other parts of the olive tree, OLE contains considerable amounts of polyphenols [37]; among them, oleuprein is the key phenolic compound found in unprocessed olive fruits and also in leaves, where it reaches about 60-90 mg/g (dry weight) [38]. The well-known antioxidant activity of oleuprein is manifold: it directly relies on its chemical structure owning an ortho-diphenolic group able to scavenge reactive oxygen species (ROS) via hydrogen donation and to stabilize oxygen radicals via an intramolecular hydrogen bond. In addition, oleuprein provides an indirect antioxidant activity by stimulating the expression of intracellular antioxidant enzymes and increasing the level of nonenzymatic antioxidant molecules [38].