APMIS | 2021
Implant‐associated osteomyelitis: Development, characterisation, and application of a porcine model
Abstract
Worldwide, there has been an ongoing increase in the number of bone infections that lead to amputations and lifelong disability, affecting millions of people every year [1,2]. Consequently, bone infections constitute a substantial economic burden in terms of patients, physicians, hospitals and healthcare systems [1,2]. When applied to patients, the term ‘bone infection’ can include prosthetic joint infections (PJIs), fracture-related infections (FRIs), implant-associated osteomyelitis (IAO), chronic osteomyelitis (CO), osteomyelitis in children and diabetic foot osteomyelitis (DFO) [3]. Presently, DFO is the leading cause of lower extremity amputations, and it is estimated that a lower limb is lost every 30 s due to DFO [4,5]. The increased number of bone infections is mainly due to an increase in the size of the elderly population, an increased prevalence of diabetes and an increase in the number of joint prostheses and bone fixation implants being used [1]. The persistence of the problem and the unsatisfactory proportion of positive treatment outcomes implies that the current prophylaxis and treatment strategies are incomplete despite best practice [2]. Therefore, future research must focus on prevention, diagnosis and treatment of bone infections. However, the development of effective new approaches and techniques will depend on preclinical testing and evaluations performed in reliable animal models. In this dissertation, a novel porcine IAO model is presented. The publications referred to (I–IX) describe the development, characterization and application of this model. Chronic bacterial infections are generally caused by biofilm-forming bacteria [6]. Therefore, it is surprising that most reports regarding bacterial biofilms are based on in vitro observations, because these laboratory findings cannot be extrapolated into clinical settings (VIII) [7]. Consequently, there are many problems associated with treating patients who have chronic biofilm-based infections, including bone infections. In addition, the increasing prevalence of antimicrobial resistance means that new treatments for chronic infectious diseases are urgently required [8]. The porcine IAO model has generated new relevant in vivo observations regarding biofilms (II, VI, VIII). In particular, studies have shown that biofilms do not simply involve artificial surface attachment; therefore, the old dogma used to describe biofilms in terms of a ‘race for the surface’ seems to be clinically inadequate (II, VI, VIII). Biofilm formation also affects tissues, and research into both tissue and implant biofilms is equally important for evaluating chronic bone infections. Promising new approaches to prevent biofilm formation in orthopaedic research include the following: 1) modification of implant surfaces to prevent bacterial adhesion, 2) coating of implants so that they can elute high concentrations of antibiotics locally (without causing systemic toxicity), 3) new drugs directed against bacterial adhesion molecules or quorum sensing and 4) the development of vaccines against biofilm-forming bacteria [9]. All of these new technologies for combating osteomyelitis may be tested using the porcine IAO model. During the past 5 years, the porcine IAO model has been applied in several studies [10– 13]. In brief, the model was used as the basis of an EU HORIZON 2020 Research and