Robust rapid-setting antibacterial liquid bandages

Abstract

Bandaging is a steadfast but time-consuming component of wound care with limited technical advancements to date. Bandages must be changed and infection risk managed. Rapid-set liquid bandages are efficient alternatives but lack durability or inherent infection control. We show here that antibacterial zinc (Zn) and copper (Cu) species greatly enhance the barrier properties of the natural, waterproof, bio-adhesive polymer, shellac. The material demonstrated marked antibacterial contact properties and, in ex-vivo studies, effectively locked-in pre-applied therapeutics. When challenged in vivo with the polybacterial bovine wound infection 'digital dermatitis', Zn/Cu-shellac adhered rapidly and robustly over pre-applied antibiotic. The bandage self-degraded, appropriately, over 7 days despite extreme conditions (faecal slurry). Treatment was well-tolerated and clinical improvement was observed in animal mobility. This new class of bandage has promise for challenging topical situations in humans and other animals, especially away from controlled, sterile clinical settings where wounds urgently require protection from environmental and bacterial contamination.

Figure 1

In vitro characterization of liquid bandages. (a) E. coli concentration (log CFU/mL) after 24 h incubation on a range of barrier surfaces in a dynamic contact killing assay. The dotted line represents the assay’s limit of detection (LOD) of 1.7 log CFU/mL. (b) Copper and zinc release from barriers into the culture medium (lysogeny broth) during the contact killing assay as determined by inductively coupled plasma optical emission spectroscopy. (c) A combined plot of contact killing ability (log CFU/mL) and total metal release (the sum of copper and zinc), with colour coded outcomes. Ideal material characteristics (antibacterial contact killing with minimal metal release) is indicated by the green region and was best achieved by material CAZ (star symbol). Control (i.e. barrier free) results are denoted by the letter ‘L’. (d) Exemplification of barrier formation upon application of CAZ to a polyethylene surface. Helium ion microscopy images of (e) surface (scale bar, 200 µm) and (f) cross section (scale bar, 50 µm), respectively, of the CAZ barrier. Error bars represent experimental standard deviations.

Figure 2

Barrier degradation and antibiotic locking. (a) Mass losses of barriers upon exposure to increasing amounts of simulated slurry for dried materials without (shellac) or with (CAZ) the presence of antimicrobial metal ions in their formulation (n = 3). (b) Ex vivo losses of antibiotic spray (quantified by loss of its dye, Patent Blue V) in simulated slurry (75 mMol/kg ammonium carbonate; n = 4) in the absence or presence of the CAZ barrier, with statistical analysis via two-tailed Mann–Whitney U test. Error bars represent experimental standard deviations.

Figure 3

In vivo proof of principle testing in farm animals with digital dermatitis. (a, b) Digital dermatitis lesion (c) with antibiotic applied (d) immediately followed by CAZ barrier to form a bandage on day 0. The subsequent images show the exact same region (e) on day 2, (f) day 4 and (g, h) day 7. (i) Barrier integrity, assessed by the blind scoring of (coded) images after CAZ application (Day 0) and then at days 2 and 7. Dark blue represents effective barrier coverage; light blue is clear residual barrier and white means no obviously visible barrier. (j) Mobility scores on day 0 and after 7 days (n = 7), with statistical analysis by single tail Wilcoxon matched-paired test.