2.2.4. Silver Nanoparticles

Silver proved its bactericidal activities against many bacteria since 1000 B.C. Now silver is used as an antiseptic, antibacterial, and antitumor agent [299]. Because of their strong antibacterial activity against both Gram-positive and Gram-negative bacterial strains, silver nanoparticles were widely used for fabricating antibacterial nanocomposite-based scaffolds and coated implants [235,237]. Furthermore, silver may be combined with different materials such as CNT [300], chitosan, HA [301], and manganite [302] to get a specific function. Ag-doped or coated implants allow reducing the number of bacterial infections without interfering with bone cell growth in the body (Figure 16 [303]). The antimicrobial activity of Ag has been reported against *Escherichia coli* [304], *Candida albicans* [11], *Vibrio cholera* [305], and *Staphylococcus aureus* [306].

**Figure 16.** Schematic diagram representing mechanisms of action of Ag nanoparticles for antibacterial action (adapted with permission from Elsevier © 2018 [303]). (**A**) AgNP diffusion and uptake into the bacterial cell. (**B**) Destabilization of ribosomes. (**C**) Enzyme interaction. (**D**) Interruption of electron transfer chain. (**E**) Reactive oxygen species (ROS). (**F**) DNA damage. (**G**) Cell death.

In addition to antibacterial activity, Ag nanoparticles promote wound healing, reduce scar formation, and reduce inflammation [307]. Silver nanoparticles have many applications as antimicrobial agents when combined with different biological substances [308]. A micrometer-sized surface-enhanced Raman spectroscopy (SERS) substrate, core–shell microparticles composed of solid carbonate core coated with silver nanoparticles, and polyhedral multishell fullerene-like structure were developed for biomedical applications [309]. Soft poly(vinyl alcohol) (PVA) hydrogel films containing silver particles prepared on solid biodegradable poly(l-lactic acid) (PLLA) exhibit both antibacterial and reduced cell adhesion properties [310]. Biocompatible maleimide-coated silver nanoparticles (Ag NPs) can be used as co-cross-linkers for the preparation of a nanocomposite gelatin-based hydrogel. Covalently bound Ag nanoparticles support swelling and drug release properties of composite hydrogel without producing toxicity [311]. In situ fabricated Ag NPs (4-19 nm) and immobilized on titanium by using a plasma immersion ion implantation process motivated osteoblast differentiation in rat bone marrow stem cells (BMSCs) [312]. Patrascu et al. [313] fabricated collagen/hydroxyapatite-silver nanoparticles (COLL/HA-Ag)-based antiseptic composite for biomedical applications.
