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A collaborative study, which includes contributions from the Nuffield Department of Orthopaedics, Rheumatology and Musculoskeletal Sciences (NDORMS) researchers Aaron Crowther and supervisor Dario Carugo, explores new ways to model bladder biology and infection, allowing evaluation of antimicrobial therapies under physiologically relevant conditions.

Bacteria on P-FLO Organoid under Flow Conditions
Microscopy image of bacterial cells after exposure to flow (using the P-FLO device) on the bladder microtissue model

Urinary tract infections (UTIs) remain a major global health challenge, with high recurrence rates and growing antimicrobial resistance contributing to an estimated 260,000 deaths annually. Current laboratory susceptibility tests often fail to predict real-world treatment outcomes, underscoring the need for physiologically relevant infection models.

A recent study led by Beyond Antibiotics researcher, Dr Ramon Garcia Maset, in collaboration with Dr Aaron Crowther, Postdoctoral Research Assistant in Antimicrobial Interventions at NDORMS and Mr Davide De Grandi, who were co-supervised by Prof Jennifer Rohn at University College London and Dr Dario Carugo, Associate Professor of Biostimulation and Immunological Engineering at the Botnar Institute, deploys innovative models as platforms to better replicate the bladder environment:

  • 3D-UHU – a three-dimensional urothelial microtissue model
  • P-FLO – a novel mesofluidic system incorporating realistic flow dynamics

The team showed that microenvironmental complexity and mechanical forces significantly influenced the behaviour of uropathogenic E. coli and the effectiveness of antibiotics and bacteriophages. While nitrofurantoin showed strong activity in standard assays, it was less effective in advanced models. Similarly, bacteriophage therapy and combination treatments demonstrated variable performance depending on physiological conditions and flow dynamics.

 

Read the full story in the Nuffield Department of Orthopaedics, Rheumatology and Musculoskeletal Sciences website.