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Nanomaterials 2018, 8, 681 2 of 25 applications [14–16]. AgNPs are a class of zero-dimensional materials with distinctive morphologies, having a size ranging from 1 nm to 100 nm [17]. As to the methods of obtaining AgNPs, different strategies were successfully used, thanks to the intrinsic versatility of silver metal and silver-based compounds, including physical [18,19], chemical [20,21], physicochemical [22,23], and biological synthesis approaches [24,25]. However, given the facile and safe process, reduced economic implications, and repeatability and reproducibility of experimental results, the method most used in the preparation of AgNPs is represented by the chemical reduction of silver salts by sodium citrate or sodium borohydrate [26,27]. In addition to their intrinsic antimicrobial-related applications, AgNPs were thoroughly explored thanks to their beneficial size-related physicochemical effects exhibited in novel electronic, magnetic, catalytic, and optical materials [28,29]. Special interest is oriented toward improving the stability of AgNPs, since a particular limitation of their antimicrobial-related use arises from their instability in bacteria-rich environments, and consequently, diminution or deprivation of their anti-pathogenic activity. In order to improve the stability of AgNPs in solution, many inorganic and organic [30,31], synthetic and natural [32,33], and biotic and abiotic materials were used as capping agents [34]. Though the precise anti-pathogenic mechanism of silver nanoparticles remains to be clarified, it is postulated that nanosilver-based systems exert their antimicrobial effects through the following phenomena: (a) microbial membrane damage, caused by the physicochemically guided attachment of AgNPs on the cell surface, and subsequent structural and functional alterations (such as gap formation, membrane destabilization, membrane piercing, and cytoplasm leakage); and (b) microbial sub-cellular structure damage, caused by the release of free Ag+ ions and subsequent reactive oxygen species (ROS) generation or essential macromolecule (proteins, enzymes, and nucleotides) inactivation [35–37]. Still, the most remarkable mechanistic mode of AgNP-based antimicrobial effects is represented by their adhesion to microbial cells, ROS and free-radical generation, microbial wall piercing and penetration inside cells, and modulation and modification of microbial signal-transduction pathways [38]. Metallic silver ions are strong antimicrobials themselves, but they are easily isolated by phosphate and chloride functions, proteins, and different cellular components [39]. The intrinsic biocide or biostatic activity of AgNPs is strongly influenced by different physicochemical features, including morphology, size, oxidation and dissolution states, surface charge, and surface coating [37,40]. The effectiveness of nanosilver-based biomaterials as promising antimicrobial agents was experimentally assessed against a wide range of medically relevant planktonic and sessile pathogenic microorganisms, including bacteria [41,42], viruses [43,44], fungi, and yeasts [45,46]. The impressive antimicrobial activity of AgNPs is a solid starting point for the design, development, and implementation of new and performance-enhanced nanosilver-based biomedical products, such as anticancer agents, drug-delivery platforms, orthopedic materials and devices [47], bandages, antiseptic sprays, and catheters [48]. As a consequence of the impressive applicability of AgNPs in the fields of nanotechnology, biomedicine, and environment, there is a continuous need for the development of cost-effective methods for the synthesis of AgNPs [49]. The translation of silver-based nanotechnology to clinical applications requires not only the development of safe, simple, eco-friendly, and cost-effective methods for the synthesis of silver nanoparticles, but also a thorough understanding of the related physicochemical particularities, in vitro and in vivo effects, biodistribution, safety control mechanisms, pharmacokinetics, and pharmacodynamics of AgNPs [48]. 2. Antibacterial Characteristics of Silver Nanoparticles Silver nanoparticles attracted tremendous interest in the biomedical field, thanks to their attractive and unique nano-related properties, including their high intrinsic antimicrobial efficiency and non-toxic nature. Among the manifold potential applications of AgNPs in this particular domain, impressive attention and efforts were lately directed toward their promising implications in wound dressing, tissue scaffold, and protective clothing applications [50,51]. Some essential aspects relatedPDF Image | Biomedical Applications of Silver Nanoparticles
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