Therapeutics and Clinical Risk Management (Dec 2020)
Bacterial Biofilm Components Induce an Enhanced Inflammatory Response Against Metal Wear Particles
Abstract
Ulrike Dapunt,1 Birgit Prior,2 Jan Philippe Kretzer,3 Thomas Giese,4 Yina Zhao1 1Center for Orthopedics, Trauma Surgery and Spinal Cord Injury, Heidelberg University Hospital, Heidelberg 69118, Germany; 2Department of Anesthesiology, Heidelberg University Hospital, Heidelberg 69120, Germany; 3Laboratory of Biomechanics and Implant Research, Center for Orthopedics, Trauma Surgery and Spinal Cord Injury, Heidelberg University Hospital, Heidelberg 69118, Germany; 4Institute for Immunology, Heidelberg University, Heidelberg 69120, GermanyCorrespondence: Ulrike DapuntCenter for Orthopedics, Trauma Surgery and Spinal Cord Injury, Heidelberg University Hospital, Schlierbacher Landstrasse 200a, Heidelberg 69118, GermanyTel + ± 49-6221-56-25000Email [email protected]: Aseptic implant loosening is still a feared complication in the field of orthopaedics. Presumably, a chronic inflammatory response is induced by wear particles, which leads to osteoclast generation, bone degradation and hence loosening of the implant. Since it has been demonstrated in the literature that most implants are in fact colonized by bacteria, the question arises whether aseptic implant loosening is truly aseptic. The aim of this study was to investigate a possibly enhanced inflammatory response to metal wear particles in the context of subclinical infection.Patients and Methods: Tissue samples were collected intra-operatively from patients undergoing implant-exchange surgery due to aseptic loosening. Histopathological analysis was performed, as well as gene expression analysis for the pro-inflammatory cytokine Interleukin-8. By a series of in vitro experiments, the effect of metal wear particles on human monocytes, polymorphonuclear neutrophiles and osteoblasts was investigated. Additionally, minor amounts of lipoteichoic acid (LTA) and the bacterial heat shock protein GroEL were added.Results: Histopathology of tissue samples revealed an accumulation of metal wear particles, as well as a cellular infiltrate consisting predominately of mononuclear cells. Furthermore, high expression of IL-8 could be detected in tissue surrounding the implant. Monocytes and osteoblasts in particular showed an increased release of IL-8 after stimulation with metal wear particles and in particular after stimulation with bacterial components and wear particles together.Conclusion: We were able to show that minor amounts of bacterial components and metal wear particles together induce an enhanced inflammatory response in human monocytes and osteoblasts. This effect could significantly contribute to the generation of bone-resorbing osteoclasts and hence implant-loosening.Keywords: aseptic loosening, metal wear particles, biofilm, implant-associated infection, Interleukin-8
