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Unique in vivo tests were conducted through the use of a fistulated ruminant, providing an ideal environment with a diverse and vibrant microbial community. Utilizing such a procedure can be especially invaluable for investigating the performance of antimicrobial materials related to human and animal related infections. In this pilot study, it is shown that the rumen of a fistulated animal provides an excellent live laboratory for assessing the properties of antimicrobial materials. We investigate microbial colonization onto model nanocomposites based on silver (Ag) nanoparticles at different concentrations into polydimethylsiloxane (PDMS). With implantable devices posing a major risk for hospital-acquired infections, the present study provides a viable solution to understand microbial colonization with the potential to reduce the incidence of infection through the introduction of Ag nanoparticles at the optimum concentrations. In vitro measurements were also conducted to show the validity of the approach. An optimal loading of 0.25 wt% Ag is found to show the greatest antimicrobial activity and observed through the in vivo tests to reduce the microbial diversity colonizing the surface.