Ex Vivo Porcine Dermal Model as a Bridge Between in Vitro and in Vivo Screening for Anti-Biofilm Efficacy

Reported here is the development and implementation of an ex vivo porcine dermal model of mature biofilm compatible for evaluation of an array of wound care therapies. The major advantages of this model system are the use of a natural porcine skin matrix and the relatively high throughput format of the assays in determining the effect of wound care technologies on biofilm prevention and/or the eradication of existing biofilm.

Microbial biofilms play an important role in the prolonged inflammation state of wounds, and the in vitro models are in general poor predictors of the treatment efficacy in vivo. The ex vivo model described here presents a significantly higher challenge compared to in vitro biofilm models grown on abiotic surfaces. This model also allows for screening of an array of test article formats, from solutions to semi-solid and solid dressings. We describe here several different formats of the model that vary in both the size of the “wound” and the explant itself.

Efficacy of two different topical wound care formulations: a) nitric oxide (NO)-releasing semi-solid dressing, and b) peptide-based polyurethane wound dressing, is compared in a series of studies, from in vitro to ex vivo to in vivo biofilm models to show the difference in the relative efficacy depending on the model. For example, while 0.5% solution of NO technology reduced overall Pseudomonas aeruginosa biofilm load by ≥6 logs, the semi-solid formulations at 2% load of the active had similar efficacy in one version of the ex vivo model (7/16” diameter) or up to four log reduction using the larger ex vivo model (2x2” in size). These data illustrate the relevance of this model in optimizing formulations prior to moving to animal studies.