A Novel High-Throughput Ex Vivo Ovine Skin Wound Model for Testing Emerging Antibiotics
September 16th, 2022
The protocol describes a step-by-step method to set up an ex vivo ovine wounded skin model infected with Staphylococcus aureus. This high-throughput model better simulates infections in vivo compared with conventional microbiology techniques and presents researchers with a physiologically relevant platform to test the efficacy of emerging antimicrobials.
Overview
This protocol outlines a method for establishing an ex vivo ovine wounded skin model infected with Staphylococcus aureus. This model provides a more physiologically relevant platform for testing the efficacy of new antimicrobials compared to traditional microbiology techniques.
Key Study Components
Area of Science
- Microbiology
- Infectious Diseases
- Pharmacology
Background
- The model simulates in vivo infections more accurately.
- It allows for greater control over drug design and formulation.
- Reduces reliance on purpose-bred animals.
- Facilitates faster clinical translation of topical antimicrobials.
Purpose of Study
- To determine the antimicrobial efficacy of novel formulations.
- To provide a representative wound environment for testing.
- To enable rapid and reproducible results.
Methods Used
- Ex vivo ovine skin model setup.
- Infection with Staphylococcus aureus.
- Aseptic technique for tissue processing.
- Dry heat sterilization of tools at 200 degrees Celsius.
Main Results
- Successful establishment of the wound model.
- Demonstrated antimicrobial efficacy of tested formulations.
- Highlighted challenges such as contamination and dexterity.
- Emphasized the importance of strict aseptic techniques.
Conclusions
- The model is effective for preclinical antimicrobial testing.
- It offers a viable alternative to traditional methods.
- Future studies can build on this model for further research.
Frequently Asked Questions
Executive Industry Relevance
High attrition and escalating costs in antimicrobial discovery demand robust, predictive preclinical models that enable fail-fast, fail-cheap decision-making. The ex vivo ovine skin wound model provides a physiologically relevant, high-throughput platform for evaluating antimicrobial efficacy during lead optimization, reducing reliance on animal studies and accelerating translational timelines. This model directly supports portfolio triage and risk-adjusted advancement of topical anti-infective candidates targeting skin and soft tissue infections.
Strategic Applications in Biopharma R&D
Early Discovery & Target Validation
- Enables interrogation of antimicrobial activity in a tissue-relevant infection context.
- Supports functional validation of lead compounds against clinically relevant pathogens.
- Facilitates mechanistic de-risking by modeling pathogen-tissue interactions.
- Improves predictive confidence for downstream in vivo studies.
Screening & Assay Development
- Provides a reproducible, quantitative platform for high-throughput efficacy screening.
- Standardizes infection and readout conditions for reliable compound comparison.
- Generates colony forming unit (CFU) data to support quantitative assessment of antimicrobial potency.
- Enables rapid iteration and optimization of drug formulations.
Translational & Preclinical Research
- Aligns preclinical testing with disease-relevant tissue environments.
- Reduces and refines animal use by filtering non-viable candidates early.
- Supports continuity from discovery through preclinical validation for topical anti-infectives.
- Facilitates risk-adjusted advancement decisions based on robust ex vivo data.
Pipeline & Workflow Integration
This ex vivo model bridges early discovery and preclinical validation, enabling rapid hypothesis testing and lead prioritization before animal studies.
- Discovery Biology: Supports hypothesis-driven evaluation of antimicrobial mechanisms in a controlled tissue context.
- Screening: Delivers standardized, reproducible, and quantitative efficacy data for compound triage.
- Analytics: Provides CFU-based readouts and histological confirmation of infection for comparative analysis.
- Translational Research: Reduces animal use and aligns preclinical workflows with clinical infection scenarios.
- Enterprise Reuse: Offers a scalable, cost-effective platform adaptable to diverse antimicrobial candidates.
Operational & Enterprise Impact
- Scientific Value: Increases predictive confidence and reduces mechanistic ambiguity in antimicrobial lead selection.
- Operational Value: Enables standardized, high-throughput, and reproducible efficacy testing.
- Strategic Value: Improves go/no-go decisions and capital efficiency by filtering candidates prior to animal studies.
- Portfolio Impact: Supports risk-adjusted prioritization and advancement of topical anti-infective assets.
Implementation Considerations
- Requires expertise in aseptic technique and tissue processing.
- Needs access to tissue culture, microbiology, and analytical infrastructure.
- Demands strict cross-team standardization to minimize contamination and variability.
- Adaptable to various antimicrobial classes and formulations targeting skin infections.
- Contamination control and operator dexterity are critical for reproducibility.
Biopharma FAQs
Chapters in this video
0:05
Introduction
0:53
Sterilization and Preparation of the Head
3:06
Maintenance of Skin Samples
4:18
Infection of Skin Samples
5:27
Determination of the Bacterial Load
6:32
Results: An Ex Vivo Ovine Wounded Skin Model Infected with Staphylococcus aureus
7:42
Conclusion
