Case Studies of a Simulation Workflow to Improve Bone Healing Assessment in Impending Non-Unions.

Background: The healing potential of a fracture is determined by mechanical and biological factors. Simulation-based workflows can help assess these factors to assist in predicting non-unions. The aim of this study was the introduction of two use cases for a novel patient-specific simulation workflow based on clinically available information. Methods: The used software is an extension of the "Ulm Bone Healing model" and was applied in two cases with non-union development after fracture fixation to show its principal feasibility. The clinical and radiographic information, starting from initial treatment, were used to feed the simulation process. Results: The simulation predicted non-union development and axial deviation in a mechanically driven non-union. In the case of a biological non-union, a slow, incomplete healing course was correctly identified. However, the time offset in callus bridging was discordant between the simulation and the distinctly slower healing response in the clinical case. Conclusions: The simulation workflow presented in the two clinical use cases allowed for the identification of fractures at risk for impending non-union immediately after the initial fixation based on available clinical and radiographic information. Further validation in a large non-union cohort is needed to increase the model's precision, especially in biologically challenging cases, and show its validity as a screening instrument.

Advantages and Limitations of Diabetic Bone Healing in Mouse Models: A Narrative Review.

Diabetes represents a major risk factor for impaired fracture healing. Type 2 diabetes mellitus is a growing epidemic worldwide, hence an increase in diabetes-related complications in fracture healing can be expected. However, the underlying mechanisms are not yet completely understood. Different mouse models are used in preclinical trauma research for fracture healing under diabetic conditions. The present review elucidates and evaluates the characteristics of state-of-the-art murine diabetic fracture healing models. Three major categories of murine models were identified: Streptozotocin-induced diabetes models, diet-induced diabetes models, and transgenic diabetes models. They all have specific advantages and limitations and affect bone physiology and fracture healing differently. The studies differed widely in their diabetic and fracture healing models and the chosen models were evaluated and discussed, raising concerns in the comparability of the current literature. Researchers should be aware of the presented advantages and limitations when choosing a murine diabetes model. Given the rapid increase in type II diabetics worldwide, our review found that there are a lack of models that sufficiently mimic the development of type II diabetes in adult patients over the years. We suggest that a model with a high-fat diet that accounts for 60% of the daily calorie intake over a period of at least 12 weeks provides the most accurate representation.

Radiographic, Biomechanical and Histological Characterization of Femoral Fracture Healing in Aged CD-1 Mice.

With a gradually increasing elderly population, the treatment of geriatric patients represents a major challenge for trauma and reconstructive surgery. Although, it is well established that aging affects bone metabolism, it is still controversial if aging impairs bone healing. Accordingly, we investigated fracture healing in young adult (3-4 months) and aged (16-18 months) CD-1 mice using a stable closed femoral fracture model. Bone healing was analyzed by radiographic, biomechanical and histological analysis at 1, 2, 3, 4 and 5 weeks after fracture. Our results demonstrated an increased callus diameter to femoral diameter ratio in aged animals at later time points of fracture healing when compared to young adult mice. Moreover, our biomechanical analysis revealed a significantly decreased bending stiffness at 3 and 4 weeks after fracture in aged animals. In contrast, at 5 weeks after fracture, the analysis showed no significant difference in bending stiffness between the two study groups. Additional histological analysis showed a delayed endochondral ossification in aged animals as well as a higher amounts of fibrous tissue at early healing time points. These findings indicate a delayed process of callus remodeling in aged CD-1 mice, resulting in a delayed fracture healing when compared to young adult animals. However, the overall healing capacity of the fractured femora was not affected by aging.