Ex vivo porcine vaginal mucosal model of infection for determining effectiveness and toxicity of antiseptics

Abstract

Aims: To develop a semi-high-throughput ex vivo mucosal model for determining efficacy and toxicity of antiseptics. Methods and Results: Explants (5 mm) from freshly excised, porcine vaginal mucosa were infected with methicillin-sensitive Staphylococcus aureus (1 9 10 6 CFU) at the epithelial surface for 2 h. Haematoxylin and eosin staining revealed healthy uninfected tissue and only minor disruptions in tissue infected with methicillin susceptible Staph. aureus (MSSA), which remained in outer epithelial cell layers. After 2 h infection, 10 ll of chlorhexidine digluconate (CHG, 3%), povidone-iodine (PI, 7Á5%), octenidine dihydrochloride (OCT, 0Á1%) or polyhexamethylene biguanide (PHMB, 0Á1%) was applied. Antiseptics significantly reduced MSSA (1-4 log 10 CFU/explants) after 0Á25 h to 4 h. CHG, PHMB and OCT exhibited persistence at 24 h. In broth culture, CHG 0Á012% and PI 0Á625% achieved >6 log 10 reductions at 2 h. PI-based formulations were more efficacious than unformulated PI. PI-based formulations exhibited no significant cytotoxicity on explants using an MTT assay. Conclusions: All antiseptics tested in the mucosal MSSA infection model reduced MSSA. CHG and PI were more potent in broth culture. Significance and Impact of the Study: We developed a semi-high-throughput mucosal model that can identify compounds or formulations with promising antimicrobial and limited cytotoxic properties.

Lactobacillus crispatus inhibits growth of Gardnerella vaginalis and Neisseria gonorrhoeae on a porcine vaginal mucosa model

“…PVM represents a biologically relevant model that cannot only be used to ask fundamental questions about microbial interactions, but also help translate new technologies to clinical use. While it is likely that some host/bacterial interactions are not identical between the porcine and human mucosal epithelia, PVM has proven to be useful in assessing host toxicity of potential antimicrobials and is predictive of clinical efficacy [ 38 , 77 ]. The use of probiotic Lactobacillus spp.…”

Efficacy of Skin and Nasal Povidone-Iodine Preparation against Mupirocin-Resistant Methicillin-Resistant Staphylococcus aureus and S. aureus within the Anterior Nares

“…We tested the antimicrobial activity of two povidone-iodinebased preparations (5%, wt/vol) and 2% mupirocin (Bactroban Nasal [BN]) using a modified version (Fig. 1a) of a previously developed ex vivo full-thickness tissue model of MRSA infection (38). Ex vivo porcine vaginal mucosal (PVM) explants were infected with MRSA (strain Xen30) for 2 h and then treated with antimicrobials for 1 h. Treated and untreated control explants were washed in PBS plus 2% (wt/vol) porcine mucin to mimic mucociliary clearance.…”

“…We previously developed a semihigh-throughput ex vivo PVM infection model for determining efficacy and toxicity of antimicrobial agents that is translational in nature (38). Its use as a substrate for bacterial attachment and nutrition provides an alternative, cost-effective method that more closely mimics in vivo conditions than classic in vitro studies.…”

“…Explants are returned to 37°C and 7% CO 2 Ex vivo porcine vaginal mucosal (PVM) culture. In a previous publication, we describe a novel model for determining the efficacy of antimicrobial agents (38). Briefly, specimens of healthy porcine vaginal mucosa are excised from animals at slaughter in the University of Minnesota Andrew Boss Laboratory of Meat Science.…”

Can We Improve Vaginal Tissue Healing Using Customized Devices: 3D Printing and Biomechanical Changes in Vaginal Tissue

“…The porcine model is an adequate pediatric vaginal model given similar dimensions, vaginal acidity, and cervical mucus production [19]. The porcine vagina accurately represents the human vaginal irritation potential of foreign objects and substances [20]. As a first step in understanding the role of mechanotransduction on vaginal tissue healing, we used 3D printed VDs of increasing diameters to establish changes in the BMP of vaginal tissue as a function of stretch.…”