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Updated: May 3, 2026
Animal Model of Implant-Associated Infections in Mice
Published on: June 27, 2025
Real-time quantification of matrix metalloproteinase and integrin αvβ3 expression during biomaterial-associated
S Daghighi1, J Sjollema, R J B Dijkstra
1Department of Biomedical Engineering, W.J. Kolff Institute, University Medical Center Groningen, P.O. Box 196, 9700 AD Groningen, The Netherlands.j.sjollema@umcg.nl.
Abstract:
Biomaterial implants and devices increase the risk of microbial infections due to the biofilm mode of growth of infecting bacteria on implant materials, in which bacteria are protected against antibiotic treatment and the local immune system. Matrix-metalloproteinases (MMPs) and cell surface integrin receptors facilitate transmigration of inflammatory cells toward infected or inflamed tissue. This study investigates the relationship between MMP- and integrin-expression and the clearance of infecting Staphylococcus aureus around implanted biomaterials in a murine model.MMP- and integrin αvβ3-expression were monitored in mice, with and without subcutaneously implanted biomaterial samples, in the absence and presence of bioluminescent S. aureus Xen36. Staphylococcal persistence was imaged longitudinally over time using bioluminescence imaging. The activatable MMPSense®680 and integrin-targeted IntegriSense®750 probes were injected on different days after implantation and their signal intensity and localisation monitored using fluorescence imaging. After sacrifice 7 or 16 days post-implantation, staphylococci from biomaterial samples and surrounding tissues were cultured on agar-plates and presence of host inflammatory cells was histologically evaluated.MMP- and integrin-expression were equally enhanced in presence of staphylococci or biomaterials up to 7 days post-implantation, but their localisation along the biomaterial samples differed. Bacterial clearance from tissue was higher in the absence of biomaterials. It is of clinical relevance that MMP- and integrin-expression were enhanced in presence of both staphylococci and biomaterials, although the immune system in the presence of biomaterials remained hampered in eradicating bacteria during the first 7 days post-implantation.
Insights
Biomaterial implants can lead to Staphylococcus aureus infections, hindering immune response. While matrix metalloproteinases (MMPs) and integrins increase with infection and implants, they don't fully clear bacteria within the first seven days.
Area of Science:
- Biomedical Engineering
- Infectious Diseases
- Immunology
Background:
- Biomaterial implants heighten infection risk from bacteria like Staphylococcus aureus, which form protective biofilms.
- Matrix metalloproteinases (MMPs) and integrin receptors aid inflammatory cell migration to infected tissues.
- Understanding host-pathogen-biomaterial interactions is crucial for combating implant-associated infections.
Purpose of the Study:
- To investigate the relationship between matrix metalloproteinase (MMP) and integrin expression and Staphylococcus aureus clearance around biomaterial implants in a murine model.
- To assess the impact of biomaterials on the host immune response to bacterial infection.
- To evaluate the efficacy of imaging probes for monitoring MMP and integrin activity in vivo.
Main Methods:
- Mice with and without biomaterial implants were infected with bioluminescent Staphylococcus aureus Xen36.
- Longitudinal imaging using bioluminescence tracked bacterial persistence.
- In vivo fluorescence imaging monitored activatable MMP (MMPSense®680) and integrin (IntegriSense®750) probes.
- Bacterial cultures and histological analysis assessed bacterial load and host inflammatory cells post-sacrifice.
Main Results:
- Both MMP and integrin expression were elevated in the presence of Staphylococcus aureus or biomaterials up to 7 days post-implantation.
- The localization of MMP and integrin expression differed along the biomaterial samples.
- Bacterial clearance was more effective in the absence of biomaterials.
- Host inflammatory cells were present, but bacterial eradication was hampered by biomaterials during the initial 7 days.
Conclusions:
- MMP and integrin expression are upregulated during biomaterial-associated Staphylococcus aureus infections.
- Biomaterials impede the host immune system's ability to clear bacteria within the first week post-implantation.
- These findings highlight the clinical challenge of treating implant-associated infections and suggest potential targets for therapeutic intervention.
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