Surgical Classification for Preclinical Rat Femoral Bone Defect Model: Standardization Based on Systematic Review,...

Though surgical techniques profoundly influence in vivo experiments, significant heterogeneity exists in current surgeries for inducing rat femoral bone defects. Such variations reduce the reproducibility and comparability of preclinical studies, and are detrimental to clinical translation. The purposes of this study were: (1) to conduct a systematic review of rat femoral defect models, summarizing and analyzing the surgical techniques; (2) to analyze surgical design and potential pitfalls via 3D anatomy and virtual surgeries for fostering future precision research; and (3) to establish a surgical classification system, for improving the reproducibility and comparability among studies, avoiding unnecessary repetitive experiments. The online database PubMed was searched to identify studies from January 2000 to June 2022 using keywords, including rat, femur, bone defect. Eligible publications were included for a review of surgical methods. Anatomical analysis and virtual surgeries were conducted based on micro-CT reconstruction of the rat femur for further investigation and establishment of a classification system. A total of 545 publications were included, revealing marked heterogeneity in surgical methods. Four major surgical designs were reported for inducing defects from the proximal to distal femur: bone tunnel, cortical window, segmental defect, and wedge-shaped defect. Anatomical analysis revealed potential pitfalls hindering efficient clinical translation. A classification system was established according to the anatomical region, surgical design, and fixation devices. This systematic review in combination with 3D analysis and virtual surgery provides a general overview of current surgical approaches to inducing femoral defects in rats, and establishes a surgical classification facilitating preclinical research of quality and translational value.