title: A novel soft tissue model for biomaterial-associated infection and inflammation - bacteriological, morphological and molecular observations.
abstract: Infection constitutes a major risk for implant failure, but the reasons why biomaterial sites are more vulnerable than normal tissue are not fully elucidated. In this study, a soft tissue infection model was developed, allowing the analysis of cellular and molecular responses in each of the sub-compartments of the implant-tissue interface (on the implant surface, in the surrounding exudate and in the tissue). Smooth and nanostructured titanium disks with or without noble metal chemistry (silver, gold, palladium), and sham sites, were inoculated with Staphylococcus epidermidis and analysed with respect to number of viable bacteria, number, viability and gene expression of host cells, and using different morphological techniques after 4 h, 24 h and 72 h. Non-infected rats were controls. Results showed a transient inflammatory response at control sites, whereas bacterial administration resulted in higher recruitment of inflammatory cells (mainly polymorphonuclear), higher, continuous cell death and higher gene expression of tumour necrosis factor-alpha, interleukin-6, interleukin-8, Toll-like receptor 2 and elastase. At all time points, S. epidermidis was predominantly located in the interface zone, extra- and intracellularly, and lower levels were detected on the implants compared with surrounding exudate. 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.
authors.affiliation: BIOMATCELL VINN Excellence Center of Biomaterials and Cell Therapy, Box 412, 405 30 Gothenburg, Sweden; Department of Biomaterials, Sahlgrenska Academy at University of Gothenburg, Box 412, 405 30 Gothenburg, Sweden.
authors.forename: Sara
authors.initials: S
authors.lastname: Svensson
authors.affiliation: BIOMATCELL VINN Excellence Center of Biomaterials and Cell Therapy, Box 412, 405 30 Gothenburg, Sweden; Department of Biomaterials, Sahlgrenska Academy at University of Gothenburg, Box 412, 405 30 Gothenburg, Sweden.
authors.forename: Margarita
authors.initials: M
authors.lastname: Trobos
authors.affiliation: BIOMATCELL VINN Excellence Center of Biomaterials and Cell Therapy, Box 412, 405 30 Gothenburg, Sweden; Department of Biomaterials, Sahlgrenska Academy at University of Gothenburg, Box 412, 405 30 Gothenburg, Sweden.
authors.forename: Maria
authors.initials: M
authors.lastname: Hoffman
authors.affiliation: BIOMATCELL VINN Excellence Center of Biomaterials and Cell Therapy, Box 412, 405 30 Gothenburg, Sweden; Department of Biomaterials, Sahlgrenska Academy at University of Gothenburg, Box 412, 405 30 Gothenburg, Sweden.
authors.forename: Birgitta
authors.initials: B
authors.lastname: Norlindh
authors.affiliation: BIOMATCELL VINN Excellence Center of Biomaterials and Cell Therapy, Box 412, 405 30 Gothenburg, Sweden; SP Technical Research Institute of Sweden, Box 857, 501 15 Borås, Sweden.
authors.forename: Sarunas
authors.initials: S
authors.lastname: Petronis
authors.affiliation: BIOMATCELL VINN Excellence Center of Biomaterials and Cell Therapy, Box 412, 405 30 Gothenburg, Sweden; SP Technical Research Institute of Sweden, Box 857, 501 15 Borås, Sweden.
authors.forename: Jukka
authors.initials: J
authors.lastname: Lausmaa
authors.affiliation: BIOMATCELL VINN Excellence Center of Biomaterials and Cell Therapy, Box 412, 405 30 Gothenburg, Sweden; Department of Biomaterials, Sahlgrenska Academy at University of Gothenburg, Box 412, 405 30 Gothenburg, Sweden.
authors.forename: Felicia
authors.initials: F
authors.lastname: Suska
authors.affiliation: BIOMATCELL VINN Excellence Center of Biomaterials and Cell Therapy, Box 412, 405 30 Gothenburg, Sweden; Department of Biomaterials, Sahlgrenska Academy at University of Gothenburg, Box 412, 405 30 Gothenburg, Sweden. Electronic address: peter.thomsen@biomaterials.gu.se.
authors.forename: Peter
authors.initials: P
authors.lastname: Thomsen
mesh_terms: D000818:Animals; D001672:Biocompatible Materials / Q000009:adverse effects*; D048430:Cell Shape / Q000187:drug effects; D002470:Cell Survival / Q000187:drug effects; D015169:Colony Count, Microbial; D004195:Disease Models, Animal; D005260:Female; D005786:Gene Expression Regulation / Q000187:drug effects; D007249:Inflammation / Q000473:pathology*; D008422:Materials Testing; D018625:Microscopy, Atomic Force; D049329:Nanostructures / Q000648:ultrastructure; D056951:Photoelectron Spectroscopy; D010865:Pilot Projects; D019736:Prostheses and Implants; D017207:Rats, Sprague-Dawley; D013203:Staphylococcal Infections / Q000382:microbiology* / Q000473:pathology*; D013212:Staphylococcus epidermidis / Q000187:drug effects* / Q000254:growth & development / Q000648:ultrastructure; D013499:Surface Properties
chemical_list: D001672:Biocompatible Materials
keywords: Animal model; Bacteria; Infection; Inflammation; Nanotopography