title: Optimized polymeric film-based nitric oxide delivery inhibits bacterial growth in a mouse burn wound model.
abstract: Nitric oxide (NO) has many biological roles (e.g. antimicrobial agent, promoter of angiogenesis, prevention of platelet activation) that make NO releasing materials desirable for a variety of biomedical applications. Localized NO release can be achieved from biomedical grade polymers doped with diazeniumdiolated dibutylhexanediamine (DBHD/N2O2) and poly(lactic-co-glycolic acid) (PLGA). In this study, the optimization of this chemistry to create film/patches that can be used to decrease microbial infection at wound sites is examined. Two polyurethanes with different water uptakes (Tecoflex SG-80A (6.2±0.7wt.%) and Tecophilic SP-60D-20 (22.5±1.1wt.%)) were doped with 25wt.% DBHD/N2O2 and 10wt.% of PLGA with various hydrolysis rates. Films prepared with the polymer that has the higher water uptake (SP-60D-20) were found to have higher NO release and for a longer duration than the polyurethane with the lower water uptake (SG-80A). The more hydrophilic polymer enhances the hydrolysis rate of the PLGA additive, thereby providing a more acidic environment that increases the rate of NO release from the NO donor. The optimal NO releasing and control SG-80A patches were then applied to scald burn wounds that were infected with Acinetobacter baumannii. The NO released from these patches applied to the wounds is shown to significantly reduce the A. baumannii infection after 24h (∼4 log reduction). The NO release patches are also able to reduce the level of transforming growth factor-β in comparison to controls, which can enhance re-epithelialization, decrease scarring and reduce migration of bacteria. The combined DBHD/N2O2 and PLGA-doped polymer patches, which could be replaced periodically throughout the wound healing process, demonstrate the potential to reduce risk of bacterial infection and promote the overall wound healing process.
authors: Department of Chemistry, University of Michigan, Ann Arbor, MI, USA.
authors: Elizabeth J
authors: EJ
authors: Brisbois
authors: Department of Surgery, University of Michigan Medical Center, Ann Arbor, MI, USA.
authors: Jill
authors: J
authors: Bayliss
authors: Department of Environmental Health Sciences, University of Michigan, Ann Arbor, MI, USA.
authors: Jianfeng
authors: J
authors: Wu
authors: Department of Surgery, University of Michigan Medical Center, Ann Arbor, MI, USA.
authors: Terry C
authors: TC
authors: Major
authors: Department of Environmental Health Sciences, University of Michigan, Ann Arbor, MI, USA.
authors: Chuanwu
authors: C
authors: Xi
authors: Department of Surgery, University of Michigan Medical Center, Ann Arbor, MI, USA.
authors: Stewart C
authors: SC
authors: Wang
authors: Department of Surgery, University of Michigan Medical Center, Ann Arbor, MI, USA.
authors: Robert H
authors: RH
authors: Bartlett
authors: Department of Surgery, University of Michigan Medical Center, Ann Arbor, MI, USA. Electronic address: hhanda@umich.edu.
authors: Hitesh
authors: H
authors: Handa
authors: Department of Chemistry, University of Michigan, Ann Arbor, MI, USA. Electronic address: mmeyerho@umich.edu.
authors: Mark E
authors: ME
authors: Meyerhoff
mesh_terms: D000151:Acinetobacter Infections / Q000628:therapy*; D040981:Acinetobacter baumannii / Q000254:growth & development*; D000818:Animals; D000900:Anti-Bacterial Agents / Q000737:chemistry / Q000494:pharmacology; D001458:Bandages; D002056:Burns / Q000382:microbiology / Q000628:therapy*; D016503:Drug Delivery Systems; D005260:Female; D019344:Lactic Acid / Q000737:chemistry; D008567:Membranes, Artificial; D051379:Mice; D009569:Nitric Oxide / Q000737:chemistry / Q000494:pharmacology; D011100:Polyglycolic Acid / Q000737:chemistry; D000077182:Polylactic Acid-Polyglycolic Acid Copolymer; D011140:Polyurethanes / Q000737:chemistry
chemical_list: D000900:Anti-Bacterial Agents; D008567:Membranes, Artificial; D011140:Polyurethanes; D000077182:Polylactic Acid-Polyglycolic Acid Copolymer; D011100:Polyglycolic Acid; D009569:Nitric Oxide; D019344:Lactic Acid
keywords: Antimicrobial; Burn wounds; Diazeniumdiolates; Nitric oxide; Poly(lactic-co-glycolic acid)