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Research

ASSESSING THE ROLE OF IMPLANT-ASSOCIATED IMMUNE RESPONSE ON THE DEVELOPMENT OF INFECTION IN VIVO

8th Combined Meeting Of Orthopaedic Research Societies (CORS)



Abstract

Summary

An in vivo model of implant infection was developed to assess immune response. Titanium and PEEK implants were tested in the presence of an osteotomy and Staphylococcus aureus contamination. Immune response differed yet the outcome of contamination did not.

Introduction

The presence of an implant increases infection risk by reducing the number of bacteria required to cause an infection. The nature or magnitude of this risk may be influenced by the implant material. A model of implant associated osteomyelitis was developed based upon the MouseFixTM model and the development of infection and immune responses associated with either titanium or PEEK implants was investigated.

Methods

MouseFixTM titanium plates with or without Staphylococcus aureus contamination were used with a femoral osteotomy in C57bl/6 and BALB/c mice (ethical permission: 2012/15). C57bl/6 mice receiving titanium implants were sacrificed at seven time-points over 35 days after surgery (n=6 per group). In addition, PEEK implants in C57bl/6 mice and both titanium and PEEK implants in BALB/c mice were assessed at 1, 3 and 7 days. Bacteria from the implant, bone and soft-tissue were quantified. Cytokine levels in the bone, soft tissue and spleen were assessed. Lymph node cells were characterised for cytokine production by flow cytometry.

Results

Bacterial contamination led to the development of chronic osteomyelitis. The bacterial counts showed an increase at day 1 followed by an initial decrease at early time-points in all conditions. However, after day 21 the bacterial load increased again. The materials caused differences in bacterial counts at day 3. In non-infected bone, IL-4, IL-6, IL-17A and KC production was elevated. In the local lymph node there was an increase of CD3+IL4+ cells. Infected bone presented a decrease in IL-4 levels, an early increase of IL-6 and IL-10 and a late increase in IL-17 and KC; additionally, CD3+IFN-gamma+ cells were increased at early time-points and after day 21. CD3+IL-17+ cells were increased between days 7 and 21. IL-4 and IL-10 producing lymphocytes were also elevated after day 14. When comparing the materials, PEEK stimulated an increase in IL-4 and a decrease in IL-17 type response compared to titanium.

Discussion

Our results suggest a Th2-type response in uninfected and a Th17-type response in infected animals. The use of different materials altered the immune response but not the outcome of contamination.