*Nanomaterials* **2019**, *9*, 1449

#### *6.3. Antimicrobial Materials*

The tendency to use metal compounds, including the ZnO-based ones, inside polymer matrices allowed creating new multifunctional materials with antibacterial and antifungal properties [113] to be used for a wide range of sectors, including photocatalytic materials for the degradation/removal of polluting species [114,115], materials for water treatment/separation [116], antiseptic and antibacterial membranes for the biomedical sector, food packaging, special self-cleaning fabrics [117], super-hydrophobic and antibacterial surfaces, and many others [118]. The confinement/anchoring of the nanostructures inside or on the surface of the polymers allows reducing the toxicity, optimizing the useful active concentrations, and creating a synergic effect between the properties of the different phases of the composite material obtained [119]. The antibacterial properties of ZnO can also be used for food storage and preservation; among the various solutions, one of the most promising involves the creation of an active antibacterial food packaging in which the material in contact with food is able to modify its characteristics and the environment that surrounds it [120,121]. The incorporation of ZnO inside polymeric matrices allows obtaining an active food packaging able to provide the proper antibacterial properties and to increase the mechanical and thermal properties of the packaging [122]. Figure 8 summarizes the properties of these new antibacterial ZnO–polymeric materials, the main antibacterial action mechanisms, and applications in which these materials are intended.

**Figure 8.** Properties, mechanisms of action, and applications of new ZnO-based antimicrobial materials.

Electrospinning proved to be an effective and promising technique for the construction of these new antibacterial tissues with multifunctional properties, as described in the examples below. Wang et al. [123] created hierarchical nanofibers of electrospun polyamide-6 (PA-6) subsequently subjected to atomic layer deposition (ALD) and a hydrothermal method for the deposition and growth of ZnO "water lily"- and "caterpillar"-like NRs. They then studied the antibacterial properties against *S. aureus* and found that the caterpillar-like NRs had better antibacterial activities, as indicated by the larger diameter of the inhibition zone; however, further studies are needed to understand the contributions of ALD cycles and the hydrothermal reaction period to the antibacterial properties.

The photocatalytic and optical properties of ZnO can be exploited to enhance the overall antibacterial effect. Prone and co-workers [124] recently developed mats with coaxial and uniaxial fibers of PCL and Zn-based NPs by electrospinning and studied their antibacterial properties toward *E. coli* and *S. aureus* under the action of UV-A light. They used different concentrations of ZnO NPs in the 9–25 wt.% range and selected this range because no significant inhibition of planktonic growth and biofilm bacteria was previously found at concentrations below 9%. During the electrospinning process, they studied the effect caused by the addition of ZnO NPs on the surface charge density of the jet and found that, as the concentration of ZnO increased, the stretching forces exerted under the action of the electric field increased, with a consequent reduction in diameter of the fibers. The Energy-dispersive X-ray spectroscopy (EDS) results demonstrated homogeneity in the distribution of NPs within the fibers, an important aspect to guarantee the uniformity of the antibacterial properties. Moreover, in the case of coaxial fibers, the NPs were mainly concentrated in the outer layer, due to the lower polarization of the jet's inner core, an advantageous aspect to increase the antibacterial surface extension; in the uniaxial fibers, the NPs were instead mainly confined inside. The authors also demonstrated that the presence of ZnO NPs reduced the hydrophobicity of the tissue compared to the use of pristine PCL fibers; moreover, the ZnO NPs facilitated the degradation of PCL, reducing its crystallinity. The turbidity test showed that the nanocomposite exerted an inhibitory action of the planktonic growth caused mainly by the release of Zn2<sup>+</sup> ions and by the photocatalytic oxidation process. In fact, if the tissue was illuminated with UV-A for 15 min before the inoculation of the bacteria, there was an increase in the photocatalytic production of ROS by the ZnO NPs, especially in the case of coaxial fibers.

Anitha et al. [125] manufactured ZnO nanoparticle-embedded cellulose acetate (CA) fibrous membranes by electrospinning and tested their optical, antibacterial, and water-repellent properties. Also, in their work, the technique of electrospinning proved to be effective in avoiding the agglomeration of the particles and maximizing the active antibacterial surface. According to the results of other studies, the antibacterial action was stronger against *S. aureus* than toward *E. coli*, probably due to the different structural nature of the bacteria cell walls, which, in the case of *S. aureus*, is presented as a multilayer porous membrane of peptidoglycan and is, thus, more susceptible to intracellular transition of nanoparticles. However, antibacterial activity against *Klebsiella pneumoniae* (*K. pneumonia*) was not reported. With regard to the wettability tests, the results of the contact-angle measurements indicated that the properties of the CA passed from hydrophilic to hydrophobic due to the ZnO impregnation. The material was suitable for use as an antibacterial hydrophobic surface without the need for further surface treatments.

Kim et al. [126] developed, by electrospinning, polyurethane (PU) nanofibers coated with polydopamine (Pdopa) using a deep coating method and subsequently put them into a ZnO NP solution as a seed layer for the hydrothermal growth of ZnO NRs. The NR film obtained adhered firmly to the surface of the PU fibers, and the results showed excellent photocatalytic and antibacterial performances under the action of light-emitting diode (LED) devices with low UV intensity. The photocatalytic activity was investigated by monitoring the degradation of a blue methylene (MB) solution by measuring the absorbance via a UV–visible spectrophotometer. The authors speculated that this material, thanks in part to its high reusability and durability, may be suitable for developing antifungal photocatalytic membranes or for degrading organic pollutants and purifying wastewater.

Malwal and Gopinath [127] synthesized CuO–ZnO composite nanofibers using electrospinning and subsequent calcination for water treatment applications; they then measured their antibacterial properties, absorption kinetics, absorption isotherm, and diffusion characteristics. The combination of antibacterial and absorption properties made this material suitable for water treatment and purification processes.

Liu and co-workers [128] fabricated electrospun nanofibers starting from ethylcellulose/gelatin solutions containing various concentrations of ZnO NPs. The presence of ZnO as a filler allowed increasing the hydrophobicity of the tissue, the water stability, and the antibacterial action toward *E. coli* and *S. aureus*, especially after UV irradiation. The authors stated that, thanks to these properties, the material could potentially be used in food packaging. Table 4 offers a summary of these results.


**4.**MainresultsofrecentstudiesonZnO-basednanomaterialsandZnO–polymericcompositenanomaterialsforsustainability

#### **7. Conclusions**

The toxicity of Zno NStr strongly depends on their physical, chemical, and morphological (shape, size) properties. Toxicity is typically concentration- and time-dependent, and there is a threshold value below which the use of ZnO nanostructures does not appear to compromise cell viability. This value is lower for smaller, spherical, and higher-aspect-ratio ZnO NPs, while it increases for nanostructures such as ZnO NRs. In fact, as the nanostructures become smaller and more reactive, with a high surface-to-volume ratio, the cell uptake increases. Solubility at different pH and aggregation phenomena are other parameters that influence cytotoxicity. Among the main causes, the production of ROS, zinc ion release, breakdown of the cell membrane, impairment of mitochondrial functions, DNA damage, and the activation of apoptosis and necrosis processes were highlighted. The selectivity of ZnO NStr toward malignant and non-malignant cell lines makes them interesting for cancer therapy applications. The in vivo studies, although they are still limited, and although the administration of nanostructures is at higher concentrations than the clinical ones, confirmed the results obtained in vitro and showed that the most compromised organs are the kidneys, liver, spleen, pancreas, lungs, reproductive system, and the brain. In conclusion, it is necessary to carry out a careful study of the doses and times of administration of the nanostructures, as well as choosing the most suitable shape and size according to the target application, for an effective and safe use of these nanomaterials. Electrospinning is able to create macroscopic textile materials and coatings that inherit the properties of the constituent ZnO NStr. Clearly, the optimum in terms of concentration and type has to be determined vs. performance in terms of biological targets by means of rational design tools such as applied statistics and experiment design. Applications in wound healing and antibacterial barriers enabled by electrospinning promise to be particularly disruptive.

**Author Contributions:** The contributions of all the authors are equal.

**Funding:** This research received no external funding.

**Conflicts of Interest:** The authors declare no conflicts of interest.

#### **References**


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