Role of Animal Models to Advance Research of Bacterial Osteomyelitis

Abstract

Osteomyelitis is an inflammatory bone disease typically caused by infectious microorganisms, often bacteria, which causes progressive bone destruction and loss. The most common bacteria associated with chronic osteomyelitis is Staphylococcus aureus. The incidence of osteomyelitis in the United States is estimated to be upwards of 50,000 cases annually and places a significant burden upon the healthcare system. There are three general categories of osteomyelitis: hematogenous; secondary to spread from a contiguous focus of infection, often from trauma or implanted medical devices and materials; and secondary to vascular disease, often a result of diabetic foot ulcers. Independent of the route of infection, osteomyelitis is often challenging to diagnose and treat, and the effect on the patient's quality of life is significant. Therapy for osteomyelitis varies based on category and clinical variables in each case. Therapeutic strategies are typically reliant upon protracted antimicrobial therapy and surgical interventions. Therapy is most successful when intensive and initiated early, although infection may recur months to years later. Also, treatment is accompanied by risks such as systemic toxicity, selection for antimicrobial drug resistance from prolonged antimicrobial use, and loss of form or function of the affected area due to radical surgical debridement or implant removal. The challenges of diagnosis and successful treatment, as well as the negative impacts on patient's quality of life, exemplify the need for improved strategies to combat bacterial osteomyelitis. There are many in vitro and in vivo investigations aimed toward better understanding of the pathophysiology of bacterial osteomyelitis, as well as improved diagnostic and therapeutic strategies. Here, we review the role of animal models utilized for the study of bacterial osteomyelitis and their critically important role in understanding and improving the management of bacterial osteomyelitis.

In vitro and in vivo assessment of caprine origin Staphylococcus aureus ST398 strain UTCVM1 as an osteomyelitis pathogen

“…A secondary benefit of this model was the ability to investigate initial clearance of ST398 via local antimicrobial-laden implant placement. This model, based upon previously published literature ( Sodnom-Ish et al, 2021 ), and fulfilling the main tenants of an animal model of osteomyelitis ( Billings and Anderson, 2022 ), had a success rate of 50% in rats inoculated with SA but not treated with any antibiotic and 20% of rats challenged with SA and a low dose of antibiotic. Success was defined as clinical osteomyelitis lesions and positive SA recovery.…”

“…This may include an in vivo dose curve of ST398 in comparison to a more widely characterized sequence type, such as USA300 or UAMS1 to add clarity regarding the interspecies potential of ST398 to establish osteomyelitis. It is suggested that this occur either in rats or rabbits, as rabbits are well-suited to dose-curves and pathogenesis investigation ( Billings and Anderson, 2022 ). Once established, there may be value in investigating for intracellular bacteria from harvested bone, whether that is through TEM or in vivo monitoring techniques to evaluate viability of bone cells.…”

“…Briefly, the procedure operated under the premise of creating bone trauma, introducing a high dose of planktonic bacteria locally, and placing foreign material within traumatized bone to provide a nidus for bacterial colonization. This procedure fulfills the main tenants of osteomyelitis induction in animal models ( Guarch-Pérez et al, 2021 ; Billings and Anderson, 2022 ). All procedures were performed in a biosafety cabinet in adherence to BSL-2 safety protocols.…”

“…Bacterial inoculums were prepared for cell culture by growing each of the three bacterial strain types overnight in 5mL of tryptic soy both (TSB) at 35°C with aeration (Bow et al, 2020;Sodnom-Ish et al, 2021;Billings and Anderson, 2022). Bacteria were harvested by centrifugation (10 minutes at 4300 X g), washed twice in 5mL of Hank's balanced salt solution (HBSS) and resuspended in Minimum Essential Media a (a-MEM) (Thermo Fisher Scientific) with 10% fetal bovine serum (FBS) as described by Tucker et al (2000).…”

Application of Direct Electric Current in a Model of Osteomyelitis in Rats

“…Рост числа высокоэнергетических травм в гражданских условиях, а также в условиях боевых действий, ведет к росту числа случаев использования металлических имплантатов в ортопедо-травматологической практике [1]. Одним из наиболее опасных осложнений, связанных с хирургической установкой ортопедических устройств (устройства для фиксации переломов, протезы суставов), является остеомиелит, который вызывается инфекционными микроорганизмами и приводит к прогрессирующему разрушению и потере костной ткани [2]. Несмотря на совершенствование технологий лечения, количество таких осложнений продолжает неуклонно расти [3; 4], что требует дальнейшей разработки эффективных способов профилактики и ликвидации остеомиелитического процесса.…”