Silver nanoparticles (AgNPs) might overcome the limitations of standard silver compounds. Due to their increased surface-to-volume ratio, AgNPs are more potent at reduced concentrations, thus lowering their toxicity. Pure silver nanoparticles can modulate anti-inflammatory cytokine release, in order to promote rapid wound closure without increasing scarring [7]. By inducing the differentiation of myofibroblasts from normal fibroblasts, AgNPs promote wound contractility, thus accelerating the healing process [21]. Moreover, AgNPs stimulate epidermal re-epithelialization through the proliferation and relocation of keratinocytes [21]. However, Szmyd et al. reported that higher concentrations of AgNPs decrease keratinocyte viability, metabolism, as well as migration and differentiation of these cells, through the activation of caspase 3 and 7 (proteases involved in programmed cell death) and dose-dependent DNA damage [22]. In order to reduce side effects, silver nanoparticles can be used in low doses along with antimicrobial drugs to achieve increased efficiency. This nanomaterial proved a high bacteria-killing performance against Gram negative pathogens and promoted wound healing [24]. Similar results have been reported by Holban et al. who coated polyester-nylon dressings with AgNPs which interfered with bacterial colonization as well as biofilm synthesis, while maintaining a low toxicity profile [25].

The main anti-bacterial mechanism of AgNPs is creating sulfuric bonds with either bacterial cell membrane proteins or thiol groups of various enzymes, especially those involved in the respiratory chain, thus leading to apoptosis [21]. Moreover, since DNA contains sulfurous and phosphorous bonds, AgNPs can interfere with DNA synthesis during cell division, thus inhibiting bacterial multiplication [21].

Moreover, silver nanoparticles were used for numerous clinical trials in the therapy of wounds, especially burns and chronic wounds (i.e., diabetic ulcers) [27]. Currently, there are some commercially available dressings containing AgNPs. Such example is Acticoat©-wound dressing containing AgNPs with average size of 15 nm. The proved properties of Anticoat© are: wound healing, infection reduction on the site of the wound, and pain reduction, aspects observed in most tested patients. However, this coating is still under investigation for the therapy of burns. Recent clinical trials concluded that Anticoat© may be efficient in avoiding infections in burns when applied together with silver sulphadiazine and chlorhexidine digluconate cream [28].

Gold nanoparticles (AuNPs) represent a solid option when it comes to wound therapy due to their chemical stability and capacity of absorbing near infrared light, while, at the same time, being relatively easy to synthetize [17]. Moreover, by tuning the surface plasmon resonance, AuNP gels gain thermoresponsiveness, as described by Arafa et al., who demonstrated their antibacterial and healing properties both in vitro and in vivo, backed by histopathologic examinations [10]. AuNPs can either directly target the bacterial cell wall, or they can bind to bacterial DNA, blocking the double-helix from uncoiling during replication or transcription, thus exerting bactericidal and bacteriostatic properties. 

Zinc oxide nanoparticles (ZnONPs) represent a reliable antibacterial agent, by inducing bacterial cell membrane perforations. Moreover, when incorporated in hydrogel-based wound dressings [7], the overall contact time is increased, promoting keratinocyte migration, thus improving re-epithelialization [21]. In addition, in a recent study, a microporous chitosan hydrogel/ZnONPs dressing presented a high capacity of absorbing wound exudates and enabled the formation of hemostatic blood clots, while also displaying antibacterial properties with little cytotoxicity [16].

However, the intrinsic high toxicity of these material limit their usage in wound healing therapies [7]. For example, high concentrations of ZnONPs are associated with mitochondrial dysfunction in keratinocytes, causing the release of lactate dehydrogenase. Moreover, ZnONPs produce reactive oxygen species, while also inhibiting the expression of superoxide dismutase and glutathione peroxidase genes in human keratinocytes, inducing cell membrane oxidative stress and apoptosis. In addition, it has been described that ZnONPs generate carcinogenic transformations [32].

In a skin wound mouse model, ZnONPs achieve successful wound closure and aesthetic wound healing, suggesting their capability as an effective antimicrobial tissue adhesive [34].

Nanomaterials can also act as carriers for therapeutic agents, controlling their release. Nitric oxide exhibits a crucial role in inflammatory pathways, cellular growth, angiogenesis and extracellular matrix deposition and remodeling. In addition, nitric oxide exhibits wide spectrum antibacterial properties, while also interfering with biofilm synthesis. As a result, many studies have tried to produce a delivery system with high loading capacity, controlled release and reduced cytotoxicity [7]. Nitric oxide-releasing poly(lactic-co-glycolic acid)-polyethylenimine nanoparticles were designed to provide prolonged nitric oxide release, antibacterial efficacy against methicillin-resistant Staphylococcus aureus and Pseudomonas aeruginosa, as well as accelerated wound closure in vivo [51].

Curcumin, the dynamic component of the nutritional spice turmeric, also presented interest due to its antibiotic and antioxidant properties, as well as stimulating the production of granulation tissue. A recent study attempted to increase curcumin’s poor solubility by encapsulating it into a saline-hydrogel nanoparticle vector, and the results demonstrated in vitro efficacy against methicillin-resistant Staphylococcus aureus and enhanced wound closure activity [53]. Ghaffari et al. stated that both gel and ointment preparations containing curcumin-Ampicillin solid lipid nanoparticles exhibited antibacterial effects, while also increasing wound closure rate compared to control and placebo groups, both in vitro and in vivo, without additional toxicity [54]. In addition, in a mouse model experiment, Moradi et al. studied the associated effect of pulse photo-bio-modulation with curcumin loaded super-paramagnetic iron oxide nanoparticles and reported accelerated wound healing and an important reduction in Staphylococcus aureus colonies [55].