Long bone Fractures and Fracture-related infections in Large animal models: A scoping review protocol

Fractures are one of the leading causes of hospital contact. One of the most feared complications is fracture-related infection (FRI), which continues to be a clinical challenge . The incidence of fractures and FRIs is expected to increase in the years to come, concurrently with the increased life expectancy [1]. Clinical studies of FRI are challenging to conduct due to the relatively low incidence rates and heterogeneity of cases [2, 3], highlighting the necessity of clinically representative animal models to optimise preventive measures and treatment before clinical application. Reviews on preclinical animal models of fractures [4] and FRI [5, 6] have previously been conducted. However, these reviews include small animals that comprise most of the identified animal models (i.e. rodents, mice) [5-7] and not larger animals (e.g. pigs, sheep, goats, dogs). However, distinct differences between humans and small animals exist [8, 9]. Consequently, the scope of this review will be long bones in large animals, considering human similarities in terms of anatomy, immune response, pathophysiology in bone structure and healing, as well as clinically relevant osteosynthesis material and antimicrobial therapy (prophylaxis and treatment) [9, 10]. Large animals are in this review defined as the traditional large animal species used for orthopaedic bone research – pigs, sheep, goats and dogs – not including cattle and horses. This comprehensive scoping review will combine the interconnected areas of fractures and fracture-related infections in long bones of large animals, focusing on specific animal species and outcome measures. Thus, this scoping review will add novelty with its specific focus and guidance excluding small animal, non-union, and human studies. The objective is to identify available large animal models investigating long bone fractures and FRIs, highlighting key concepts and potential gaps to guide future research projects[11]. A scoping review approach was chosen as it serves this purpose[12].