A review of mouse critical size defect models in weight bearing bones

Current and future advances in orthopedic treatment are aimed at altering biological interactions to enhance bone healing. Currently, several clinical scenarios exist for which there is no definitive treatment, specifically segmental bone loss from high-energy trauma or surgical resection — and it is here that many are aiming to find effective solutions. To test experimental interventions and better understand bone healing, researchers employ critical size defect (CSD) models in animal studies. Here, an overview of CSDs is given that includes the specifications of varying models, a discussion of current scaffold and bone graft designs, and current outcome measures used to determine the extent of bone healing. Many promising graft designs have been discovered along with promising adjunctive treatments, yet a graft that offers biomechanical support while allowing for neovascularization with eventual complete resorption and remodeling remains to be developed. An overview of this important topic is needed to highlight current advances and provide a clear understanding of the ultimate goal in CSD research — develop a graft for clinical use that effectively treats the orthopedic conundrum of segmental bone loss.

► Defect sizes used in critical size defect (CSD) models are reviewed.
► Current scaffold designs are discussed, including manufacturing methods and results.
► Current cortical bone grafts are reviewed with regards to CSD models.
► Recent experimental interventions utilized in CSD models are discussed.
► Outcome measures, including μCT, histology, and biomechanical testing are reviewed.