Abstract
The potential of sheep in preclinical models for bone infection research – a systematic review
Introduction: Reliable animal models are critical for preclinical research and should closely mimic the disease.
With respect to route of infection, pathogenic agent, disease progression, clinical signs, and histopathological
changes. Sheep have similar bone micro- and macrostructure as well as comparable biomechanical
characteristics to humans. Their use in bone research is established, however their use in bone infection research
is limited. This systematic review will summarise the key features of the available bone infection models using
sheep, providing a reference for further development, validation, and application.
Method: This systematic review was designed according to the PRISMA guidelines and registered with
PROSPERO. Quality was assessed using SYRICLE’s risk of bias tool adapted for animal studies. PubMed, MEDLINE,
Web of Science and EMBASE were searched until March 2022. 1921 articles were screened by two independent
reviewers, and 25 were included for analysis.
Result: Models have been developed in nine different breeds. Staphylococcus aureus was used in the majority of
models, typically inoculating 108 colony forming unitsin tibial or femoral cortical defects. Infection was
established with either planktonic or biofilm adherent bacteria, with or without foreign material implanted. Most
studies used both radiological and microbiological analyses to confirm osteomyelitis.
Conclusion: There is convincing evidence supporting the use of sheep in bone infection models of clinical
disease. The majority of sheep studied demonstrated convincing osteomyelitis and tolerated the infection with
minimal complications. Furthermore, the advantages of comparable biology and biomechanics may increase the
success for translating in vivo results to successful therapies.
Introduction: Reliable animal models are critical for preclinical research and should closely mimic the disease.
With respect to route of infection, pathogenic agent, disease progression, clinical signs, and histopathological
changes. Sheep have similar bone micro- and macrostructure as well as comparable biomechanical
characteristics to humans. Their use in bone research is established, however their use in bone infection research
is limited. This systematic review will summarise the key features of the available bone infection models using
sheep, providing a reference for further development, validation, and application.
Method: This systematic review was designed according to the PRISMA guidelines and registered with
PROSPERO. Quality was assessed using SYRICLE’s risk of bias tool adapted for animal studies. PubMed, MEDLINE,
Web of Science and EMBASE were searched until March 2022. 1921 articles were screened by two independent
reviewers, and 25 were included for analysis.
Result: Models have been developed in nine different breeds. Staphylococcus aureus was used in the majority of
models, typically inoculating 108 colony forming unitsin tibial or femoral cortical defects. Infection was
established with either planktonic or biofilm adherent bacteria, with or without foreign material implanted. Most
studies used both radiological and microbiological analyses to confirm osteomyelitis.
Conclusion: There is convincing evidence supporting the use of sheep in bone infection models of clinical
disease. The majority of sheep studied demonstrated convincing osteomyelitis and tolerated the infection with
minimal complications. Furthermore, the advantages of comparable biology and biomechanics may increase the
success for translating in vivo results to successful therapies.
| Original language | English |
|---|---|
| Publication date | 2024 |
| Publication status | Published - 2024 |
| Event | Annual Meeting of the European Orthopaedic Research Society, 2024 - Aalborg, Denmark Duration: 18 Sep 2024 → 19 Sep 2024 Conference number: 32 |
Conference
| Conference | Annual Meeting of the European Orthopaedic Research Society, 2024 |
|---|---|
| Number | 32 |
| Country/Territory | Denmark |
| City | Aalborg |
| Period | 18/09/2024 → 19/09/2024 |