A novel soft tissue model for biomaterial-associated infection and inflammation
Sara
Svensson1, 2*,
Margarita
Trobos1, 2*,
Maria
Hoffman1, 2*,
Birgitta
Norlindh1, 2*,
Sarunas
Petronis2, 3*,
Jukka
Lausmaa2, 3*,
Felicia
Suska1, 2 and
Peter
Thomsen1, 2*
-
1
Institute of Clinical Sciences, Sahlgrenska Academy, University of Gothenburg, Department of Biomaterials, Sweden
-
2
University of Gothenburg, BIOMATCELL VINN Excellence Center of Biomaterials and Cell Therapy, Sweden
-
3
SP Technical Research Institute of Sweden, Chemistry, Materials and Surfaces - Medical Device Technology, Sweden
Introduction: Biomaterial-associated infection is an important complication of medical devices that often requires removal of the implant for successful healing. The mechanisms of bacterial persistence and how the host immune cells are affected by the presence of a colonized biomaterial are incompletely understood. The exploration of novel infection control strategies would be enabled by the development of experimental models allowing the quantitative determination of host-bacteria interactions in vivo. This study describes a soft tissue model for the investigation of bacteriological, morphological and molecular events taking place on the implant surface and in the surrounding exudate and tissue[1].
Materials and Methods: Smooth and nanostructured Ti disks with or without noble metal chemistry (Ag, Au, Pd) and sham sites were inoculated with a dose of 106 CFU Staphylococcus epidermidis (ATCC 35984) subcutaneously on the back of rats. Implant and sham sites were analysed after 4 h, 24 h and 72 h with respect to the number of viable bacteria and the number, viability and gene expression (TNF-α, IL-6, IL-8, IL-10, TLR2, TLR4, elastase) of host cells. The tissue response and the location of S. epidermidis in the interface tissue, were evaluated by histology and FISH, respectively. Non-infected rats were controls. Data was statistically evaluated in PASW/Statistics 18.0 and different tests were applied depending on the type of comparison (n=7-8). The study was approved by the local ethical committee for laboratory animals (Dnr 254/11).
Results and Discussion: The results revealed distinct differences between infected and control sites, e.g. in the number, type and viability of host cells surrounding the implant. Host cells at infected sites showed significantly higher gene expression activity of genes related to inflammation, bacterial recognition and tissue degradation than control sites. In the tissue, bacterial cells were primarily located in close proximity to the implant, both extra- and intracellularly (Fig 1).
Cytospin preparations of the exudate showed that both mono- and polymorphonuclear cells contained bacterial cells within the cytoplasm (Fig 2).
Comparisons between materials revealed elevated cell recruitment, higher neutrophil presence and higher pro-inflammatory gene expression in host cells surrounding noble metal coated Ti, which was in addition associated with a lower number of viable bacteria at 24 h (Fig 3).
Interestingly, all implant surfaces harboured less bacteria (ten fold) than the surrounding exudate at all time points. In addition, S. epidermidis still persisted at both material and sham sites after 72 h, indicating a need for longer-term studies.
Conclusion: This model allows detailed analysis of early events in inflammation and infection associated to biomaterials in vivo, leading to insights into host defence mechanisms in biomaterial-associated infections.
BIOMATCELL Vinn Excellence Center of Biomaterials and Cell Therapy; Swedish Research Council (grant (K2015-52X-09495-28-4); Hjalmar Svensson Research Foundation; IngaBritt and Arne Lundberg Foundation; Felix Neubergh Foundation
References:
[1] Svensson S et al. Biomaterials 2015; 41:106-121
Keywords:
Gene Expression,
Infection,
in vivo,
Implant
Conference:
10th World Biomaterials Congress, Montréal, Canada, 17 May - 22 May, 2016.
Presentation Type:
Poster
Topic:
Device-related infections
Citation:
Svensson
S,
Trobos
M,
Hoffman
M,
Norlindh
B,
Petronis
S,
Lausmaa
J,
Suska
F and
Thomsen
P
(2016). A novel soft tissue model for biomaterial-associated infection and inflammation.
Front. Bioeng. Biotechnol.
Conference Abstract:
10th World Biomaterials Congress.
doi: 10.3389/conf.FBIOE.2016.01.01642
Copyright:
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Received:
27 Mar 2016;
Published Online:
30 Mar 2016.
*
Correspondence:
Dr. Sara Svensson, Institute of Clinical Sciences, Sahlgrenska Academy, University of Gothenburg, Department of Biomaterials, Göteborg, Sweden, sara.svensson@biomaterials.gu.se
Dr. Margarita Trobos, Institute of Clinical Sciences, Sahlgrenska Academy, University of Gothenburg, Department of Biomaterials, Göteborg, Sweden, margarita.trobos@biomaterials.gu.se
Dr. Maria Hoffman, Institute of Clinical Sciences, Sahlgrenska Academy, University of Gothenburg, Department of Biomaterials, Göteborg, Sweden, maria.hoffman@biomaterials.gu.se
Dr. Birgitta Norlindh, Institute of Clinical Sciences, Sahlgrenska Academy, University of Gothenburg, Department of Biomaterials, Göteborg, Sweden, birgitta.norlindh@biomaterials.gu.se
Dr. Sarunas Petronis, University of Gothenburg, BIOMATCELL VINN Excellence Center of Biomaterials and Cell Therapy, Göteborg, Sweden, Sarunas.Petronis@sp.se
Dr. Jukka Lausmaa, University of Gothenburg, BIOMATCELL VINN Excellence Center of Biomaterials and Cell Therapy, Göteborg, Sweden, jukka.lausmaa@sp.se
Dr. Peter Thomsen, Institute of Clinical Sciences, Sahlgrenska Academy, University of Gothenburg, Department of Biomaterials, Göteborg, Sweden, peter.thomsen@biomaterials.gu.se