title: Gallium-Loaded Dissolvable Microfilm Constructs that Provide Sustained Release of Ga(3+) for Management of Biofilms.
abstract: The persistence of bacterial biofilms in chronic wounds delays wound healing. Although Ga(3+) 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 Ga(3+) 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 Ga(3+) and that the density of covalent cross-links introduced into the polyelectrolyte film (amide-bonds) controls the release rate of Ga(3+) . 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 Ga(3+) over 3 weeks, thus continuously replacing Ga(3+) 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.
authors.affiliation: Department of Chemical and Biological Engineering, University of Wisconsin, 1415 Engineering Drive, Madison, WI, 53706, USA.
authors.forename: Maggie
authors.initials: M
authors.lastname: Herron
authors.affiliation: Department of Surgery, School of Medicine, University of Colorado-Denver, 12631 E. 17th Avenue, Aurora, CO, 80045, USA.
authors.forename: Michael J
authors.initials: MJ
authors.lastname: Schurr
authors.affiliation: Department of Ophthalmology and Vision Sciences, School of Medicine, Department of Surgical and Radiological Sciences, School of Veterinary Medicine, University of California-Davis, 1423 Tupper Hall, Davis, CA, 95616, USA.
authors.forename: Christopher J
authors.initials: CJ
authors.lastname: Murphy
authors.affiliation: Department of Surgical Sciences, School of Veterinary Medicine, University of Wisconsin-Madison, 2015, Linden Dr, Madison, WI, 53706, USA.
authors.forename: Jonathan F
authors.initials: JF
authors.lastname: McAnulty
authors.affiliation: Department of Pathobiology, School of Veterinary Medicine, University of Wisconsin-Madison, 2015, Linden Dr, Madison, WI, 53706, USA.
authors.forename: Charles J
authors.initials: CJ
authors.lastname: Czuprynski
authors.affiliation: Department of Chemical and Biological Engineering, University of Wisconsin, 1415 Engineering Drive, Madison, WI, 53706, USA.
authors.forename: Nicholas L
authors.initials: NL
authors.lastname: Abbott
mesh_terms: D001458:Bandages; D018441:Biofilms / Q000187:drug effects*; D018533:Biomass; D003692:Delayed-Action Preparations; D004573:Electrolytes / Q000737:chemistry; D005708:Gallium / Q000494:pharmacology*; D007700:Kinetics; D011142:Polyvinyl Alcohol / Q000737:chemistry; D011550:Pseudomonas aeruginosa / Q000187:drug effects / Q000502:physiology; D012995:Solubility
chemical_list: D003692:Delayed-Action Preparations; D004573:Electrolytes; D011142:Polyvinyl Alcohol; D005708:Gallium
keywords: biofilms; gallium nitrate; microfilms; polymers; wound dressing