Reduction in Wound Bioburden using a Silver‐Loaded Dissolvable Microfilm Construct

Abstract

Silver is a widely used antimicrobial agent, yet when impregnated in macroscopic dressings, it stains wounds, can lead to tissue toxicity and can inhibit healing. Recently, we reported that polymeric nanofilms containing silver nanoparticles exhibit antimicrobial activity at loadings and release rates of silver that are 100x lower than conventional dressings. Here we report fabrication of composite microfilm constructs that provide a facile way to transfer the silver-loaded polymeric nanofilms onto wounds in vivo. The construct is fabricated from a silver nanoparticle-loaded polymeric nanofilm that is laminated with a micrometer-thick soluble film of polyvinylalcohol (PVA). When placed on a moist wound, the PVA dissolves, leaving the silver-loaded nanofilm immobilized on the wound-bed. In vitro, the immobilized nanofilms release <1 μg cm−2/day of silver over 30 days from skin-dermis and they kill 5 log10 CFUs of Staphylococcus aureus in 24 h. In mice, wounds inoculated with 105 CFU S. aureus presented up to 3 log10 less bacterial burden when treated with silver/nanofilms for 3 days, as compared to unmodified wounds. In uncontaminated wounds, silver/nanofilms allow normal and complete wound closure by re-epithelialization. We conclude that dissolvable microfilm constructs may overcome key limitations associated with current uses of silver in wound healing.

Gallium‐Loaded Dissolvable Microfilm Constructs that Provide Sustained Release of Ga3+ for Management of Biofilms

“…Next, we characterized the Ga 3+ release profile from PEMs of (PAH/PAA) 60.5 loaded with 24.5 ± 0.4 µg cm −2 of Ga 3+ , with and without cross-linking. Here we note that the higher loading of Ga 3+ (as compared to that reported earlier in this paper) was used to prolong the release of Ga 3+ over two weeks (the time it takes for in vivo model wound beds, reported previously, [24] to close completely). As seen in Figure 4, the amount of Ga 3+ released from the PEMs without cross-linking and PEMs with cross-linking after 24 h were 22.7 ± 0.4 and 2.5 ± 0.1 µg cm −2 , respectively.…”

“…We hypothesized that the polyeletrolyte multilayers (PEMs) could serve as nanometer-thick reservoirs for spatial confinement and localized delivery of Ga 3+ . We note that previously we reported the use of PEMs loaded with silver nanoparticles to release non-cytotoxic loadings of Ag + ions that killed planktonic bacteria in in vitro [22,23] and in vivo studies [24,25] . In this study, we move to explore ways to manage bacterial biofilms based on the localized delivery of Ga 3+ from PEMs.…”

“…[24] The PEMs were not synthesized directly on the Biobrane because the harsh conditions required to fabricate the PEMs (e.g. low pH (pH 2.5) for Ga(NO 3 ) 3 solution and T ~ 215°C for cross-linking the Ga 3+ -loaded PEMs) will cause damage to the biological components (e.g., collagen) of the dressings.…”

Nano-Engineered Biomaterials for Tissue Regeneration: What Has Been Achieved So Far?

“…Recent in vitro and in vivo work has pointed toward the unprecedented ability of AgNP to reduce inflammatory macrophage and neutrophil infiltration, to inhibit the production of inflammatory cytokines, and to regulate the expression of metalloproteinases (Wright et al, 2002;Bhol and Schechter, 2007;Tian et al, 2007;Wong et al, 2009;Liu et al, 2010;Zhang et al, 2014). Thus, it stands that the incorporation of AgNP in biomaterial dressings is expected not only to add an antimicrobial element to the scaffold but also to further improve wound healing (Lu et al, 2012a;Neibert et al, 2012;Fan et al, 2014;Herron et al, 2014). For example, a chitosan-AgNP dressing by Lu et al significantly increased the healing rate of dermal wounds 10% of the body surface area in a rat model as compared to silver sulfadiazine or chitosan film alone while the percentage of silver dissemination away from the area of injury was lower for AgNP (Lu et al, 2012a).…”

Silver Oxynitrate, an Unexplored Silver Compound with Antimicrobial and Antibiofilm Activity

“…Currently, the wound care industry is replete with Ag-based ointments and wound dressings with claimed efficacy at reducing bacterial bioburden (7,(28)(29)(30)(31)(32). However, only a few antibiofilm products exist.…”