Due to the morbidity and lethality of pulmonary diseases, new biomaterials and scaffolds are needed to support the regeneration of lung tissues, while ideally providing protective effects against inflammation and microbial aggression. In this study, we investigated the potential of nanocomposites of poly(vinylidene fluoride-co-trifluoroethylene) [P(VDF-TrFE)] incorporating zinc oxide (ZnO), in the form of electrospun fiber meshes for lung tissue engineering. We focused on their anti-inflammatory, antimicrobial, and mechanoelectrical character according to different fiber mesh textures (i.e., collected at 500 and 4000 rpm) and compositions: (0/100) and (20/80) w/w% ZnO/P(VDF-TrFE), plain and composite, respectively. The scaffolds were characterized in terms of morphological, physicochemical, mechanical, and piezoelectric properties, as well as biological response of A549 alveolar epithelial cells in presence of lung-infecting bacteria. By virtue of ZnO, the composite scaffolds showed a strong anti-inflammatory response in A549 cells, as demonstrated by a significant decrease of interleukin (IL) IL-1α, IL-6, and IL-8 expression in 6 h. In all the scaffold types, but remarkably in the aligned composite ones, transforming growth factor β (TGF-β) and the antimicrobial peptide human β defensin-2 (HBD-2) were significantly increased. The ZnO/P(VDF-TrFE) electrospun fiber meshes hindered the biofilm formation by Staphylococcus aureus and Pseudomonas aeruginosa and the cell/scaffold constructs were able to impede S. aureus adhesion and S. aureus and P. aeruginosa invasiveness, independent of the scaffold type. The data obtained suggested that the composite scaffolds showed potential for tunable mechanical properties, in the range of alveolar walls and fibers. Finally, we also showed good piezoelectricity, which is a feature found in elastic and collagen fibers, the main extracellular matrix molecules in lungs. The combination of all these properties makes ZnO/P(VDF-TrFE) fiber meshes promising for lung repair and regeneration. Impact statement Airway tissue engineering is still a major challenge and an optimally designed scaffold for this application should fulfill a number of key requirements. To help lung repair and regeneration, this study proposes a nondegradable scaffold, with potential for tuning mechanical properties. This scaffold possesses a strong anti-inflammatory character, and is able to hinder microbial infections, sustain epithelial cell growth, and provide physiological signals, like piezoelectricity. The development of such a device could help the treatment of pulmonary deficiency, including the ones induced by inflammatory phenomena, primary and secondary to pathogen infections.
Keywords: A549 cells; P. aeruginosa; S. aureus; human beta defensin; nanocomposite; piezoelectric.