Cerium Nitrate Stiffens In Vitro Skin Models and Reduces Pseudomonas aeruginosa Pathogenicity and Penetration Through Skin Models.

Abstract

Objective: Cerium nitrate (CeN) plus silver sulfadiazine (SSD) cream has been used for 40-plus years to manage burns. CeN produces a hardened eschar believed to resist bacterial colonization/infection. To evaluate this potential mechanism, we treated in vitro skin models or Pseudomonas aeruginosa with CeN and measured mechanical properties of the models and bacterial virulence, respectively. Approach: We treated three-dimensional-collagen matrix and ex-vivo-burned porcine skin with CeN and evaluated stiffness and P. aeruginosa penetration. In addition, we treated P. aeruginosa with CeN and evaluated the bacteria's motility, skin model penetration, susceptibility to be phagocytized by the human monocytic cell line THP-1, and ability to stimulate this cell line to produce cytokines. Results: CeN treatment of skin models stiffened them and made them resistant to P. aeruginosa penetration. Inversely, CeN treatment of P. aeruginosa reduced their motility, penetration through skin models (ex-vivo-burned porcine skin), and ability to stimulate cytokine production (tumor necrosis factor-α [TNF-α] and interleukin 8 [IL-8]) by THP-1 cells. In addition, CeN-treated Pseudomonas was more readily phagocytized by THP-1 cells. Finally, P. aeruginosa inoculated on CeN-treated ex-vivo-burned porcine skin was more susceptible to killing by a silver dressing. Innovation: In vitro skin models offer a platform for screening drugs that interfere with bacterial penetration into wounded tissue. Conclusion: CeN treatment reduced P. aeruginosa virulence, altered the mechanical properties of ex-vivo-burned porcine skin and collagen matrix, retarded penetration of P. aeruginosa through the skin models, and resulted in increased vulnerability of P. aeruginosa to killing by antimicrobial wound dressings. These data support the use of CeN in burn management.