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

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The persistence of bacterial biofilms in chronic wounds delays wound healing. Although Ga3+ can inhibit or kill biofilms, precipitation as Ga(OH)3 has prevented its use as a topical wound treatment. The design of a microfilm construct comprising a polyelectrolyte film that releases noncytotoxic concentrations of Ga3+ over 20 d and a dissolvable micrometer-thick film of polyvinylalcohol that enables facile transfer onto biomedically important surfaces is reported. By using infrared spectroscopy, it is shown that the density of free carboxylate/carboxylic acid and amine groups within the polyelectrolyte film regulates the capacity of the construct to be loaded with Ga3+ and that the density of covalent cross-links introduced into the polyelectrolyte film (amide-bonds) controls the release rate of Ga3+. Following transfer onto the wound-contact surface of a biologic wound dressing, an optimized construct is demonstrated to release ≈0.7 μg cm−2 d−1 of Ga3+ over 3 weeks, thus continuously replacing Ga3+ lost to precipitation. The optimized construct inhibits formation of P. aeruginosa (two strains; ATCC 27853 and PA01) biofilms for up to 4 d and causes pre-existing biofilms to disperse. Overall, this study provides designs of polymeric constructs that permit facile modification of the wound-contacting surfaces of dressings and biomaterials to manage biofilms.

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