Innovations in osteomyelitis research: A review of animal models

Abstract

Infection of bone tissue, or osteomyelitis, has become a growing concern in modern healthcare due in no small part to a rise in antibiotic resistance among bacteria, notably Staphylococcus aureus. The current standard of care involves aggressive, prolonged antibiotic therapy combined with surgical debridement of infected tissues. While this treatment may be sufficient for resolving a portion of cases, recurrences of the infection and associated risks including toxicity with long‐term antibiotic usage have been reported. Therefore, there exists a need to produce safer, more efficacious options of treatment for osteomyelitis. In order to test treatment regimens, animal models that closely mimic the clinical condition and allow for accurate evaluation of therapeutics are necessary. Establishing a model that replicates features of osteomyelitis in humans continues to be a challenge to scientists, as there are many variables involved, including choosing an appropriate species and method to establish infection. This review addresses the refinement of animal models of osteomyelitis to reflect the clinical disease and test prospective therapeutics. The aim of this review is to explore studies regarding the use of animals for osteomyelitis therapeutics research and encourage further development of such animal models for the translation of results from the animal experiment to human medicine.

Antimicrobial Peptides in the Battle against Orthopedic Implant-Related Infections: A Review

“…Therefore, future in vivo studies, with adequate animal models and more realistic scenarios, will allow to assess their potential application in orthopedic surgery. Different osteomyelitis models to assess in vivo performance of titanium implants have been recently reviewed [73,74].…”

“…As mentioned above, for market-oriented research, a complete pre-clinical validation is mandatory to comply with regulatory entities for future market implementation. Standardized assays should be followed as recommended by the FDA ( https://www.accessdata.fda.gov/scripts/cdrh/cfdocs/cfStandards/search.cfm, accessed on 1 September 2021) and EMA (https://www.ema.europa.eu/en/human-regulatory/ overview/data-medicines-iso-idmp-standards-overview, accessed on 1 September 2021), including in vivo validation with appropriate animal models, ranging from mice to dogs or goats [73,74,[140][141][142][143]. Small animal models, e.g., mice, rats, and rabbits, are cheaper and can provide important information in initial studies.…”

“…Small animal models, e.g., mice, rats, and rabbits, are cheaper and can provide important information in initial studies. Bigger models, such as dogs, present very similar bone composition and density to humans, and goats or sheep can be good models to mimic human osteomyelitis since their size allows the use of human implants rather than adapted ones [74].…”

Recent advances in the local antibiotics delivery systems for management of osteomyelitis

“…From the researchers’ overview, to be able to create a multipurpose scaffolding materials for managing different stages of osteomyelitis, many areas has to be tackled. The most important of which is creating reliable osteomyelitis models that imitates features of osteomyelitis conditions in humans’ bones which, continues to be a challenge to scientists (Roux et al., 2021 ). The current animal models employed to assess the efficacy of scaffolds for elimination of infection and regeneration of bone should be fully detailed and reproducible, with well-defined gold standard for the diagnosis of osteomyelitis, there originating sources and stage of infection in order to be able to simulate the clinical scenarios (Reizner et al., 2014 ).…”

Preclinical Testing of Radiopharmaceuticals for the Detection and Characterization of Osteomyelitis: Experiences from a Porcine Model

“…These and more aspects will be discussed in the following sections for the most commonly used animal species in osteomyelitis research: mice, rats, rabbits, pigs, sheep, and dogs. Others have reviewed the disease aspects of osteomyelitis in animals [ 18 , 19 , 20 ], but we will focus on the features that are important for testing tracers.…”