Preclinical in vivo models of fracture-related infection: a systematic review and critical appraisal.

A fracture-related infection (FRI) is an important complication that can lead to an increase in morbidity, mortality and economic costs. Preclinical in vivo models are critical in the evaluation of novel prevention and treatment strategies, yet it is important that these studies recapitulate the features of an FRI that make it such a clinical challenge. The aim of this systematic review was to survey the available preclinical models of FRIs and assess which of the key FRI-specific parameters are incorporated in these models. A comprehensive search was performed on July 1st 2017 in PubMed, Embase and Web of Science. Overall, 75 preclinical studies were identified, 97.3 % (n = 73) of which use Staphylococcus aureus as the causative microorganism. The most common mode for creation of bone instability is an osteotomy (n = 30; 40 %), followed by the creation of a defect (n = 26; 34.7 %). An actual fracture is created in only 19 studies (25.3 %). 12 (16 %) of the models include a time gap between bacterial inoculation and fixation to mimic the time-to-treatment in clinical open fracture scenarios. This systematic review reveals that animal models used in translational research on prevention and treatment of FRIs rarely incorporate all key clinical features in one model and that there is an over-representation of S. aureus in comparison to actual clinical epidemiology. To improve the relevance of these studies, existing preclinical models should be adapted or new models developed that better recapitulate the clinical condition of FRI.

Clinical management and innovation in fracture non-union.

INTRODUCTION: With the introduction and continuous improvement in operative fracture fixation, even the most severe bone fractures can be treated with a high rate of successful healing. However, healing complications can occur and when healing fails over prolonged time, the outcome is termed a fracture non-union. Non-union is generally believed to develop due to inadequate fixation, underlying host-related factors, or infection. Despite the advancements in fracture fixation and infection management, there is still a clear need for earlier diagnosis, improved prediction of healing outcomes and innovation in the treatment of non-union. AREAS COVERED: This review provides a detailed description of non-union from a clinical perspective, including the state of the art in diagnosis, treatment, and currently available biomaterials and orthobiologics.Subsequently, recent translational development from the biological, mechanical, and infection research fields are presented, including the latest in smart implants, osteoinductive materials, and in silico modeling. EXPERT OPINION: The first challenge for future innovations is to refine and to identify new clinical factors for the proper definition, diagnosis, and treatment of non-union. However, integration of in vitro, in vivo, and in silico research will enable a comprehensive understanding of non-union causes and correlations, leading to the development of more effective treatments.