ZnO-based nanomaterials are a subject of increasing interest within current research, because of their multifunctional properties, such as piezoelectricity, semi-conductivity, ultraviolet absorption, optical transparency, and photoluminescence, as well as their low toxicity, biodegradability, low cost, and versatility in achieving diverse shapes. Among the numerous fields of application, the use of nanostructured ZnO is increasingly widespread also in the biomedical and healthcare sectors, thanks to its antiseptic and antibacterial properties, role as a promoter in tissue regeneration, selectivity for specific cell lines, and drug delivery function, as well as its electrochemical and optical properties, which make it a good candidate for biomedical applications. Because of its growing use, understanding the toxicity of ZnO nanomaterials and their interaction with biological systems is crucial for manufacturing relevant engineering materials. In the last few years, ZnO nanostructures were also used to functionalize polymer matrices to produce hybrid composite materials with new properties. Among the numerous manufacturing methods, electrospinning is becoming a mainstream technique for the production of scaffolds and mats made of polymeric and metal-oxide nanofibers. In this review, we focus on toxicological aspects and recent developments in the use of ZnO-based nanomaterials for biomedical, healthcare, and sustainability applications, either alone or loaded inside polymeric matrices to make electrospun composite nanomaterials. Bibliographic data were compared and analyzed with the aim of giving homogeneity to the results and highlighting reference trends useful for obtaining a fresh perspective about the toxicity of ZnO nanostructures and their underlying mechanisms for the materials and engineering community.
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