Large animal contusion models of spinal cord injury are an essential precursor to developing and evaluating treatment options for human spinal cord injury. Reducing variability in these experiments has been a recent focus as it increases the sensitivity with which treatment effects can be detected while simultaneously decreasing the number of animals required in a study. Here, we conducted a detailed review to explore if head and neck positioning in a cervical contusion model of spinal cord injury could be a factor impacting the biomechanics of a spinal cord injury, and thus, the resulting outcomes. By reviewing existing literature, we found evidence that animal head/neck positioning affects the exposed level of the spinal cord, morphology of the spinal cord, tissue mechanics and as a result the biomechanics of a cervical spinal cord injury. We posited that neck position could be a hidden factor contributing to variability. Our results indicate that neck positioning is an important factor in studying biomechanics, and that reporting these values can improve inter-study consistency and comparability and that further work needs to be done to standardize positioning for cervical spinal cord contusion injury models.

Non-human primate (NHP) spinal cord injury experiments exhibit high intersubject variability in biomechanical parameters even when a consistent impact protocol is applied to each subject. Optimizing impact parameters to reduce this variability through experiments is logistically challenging in NHP studies. Finite element models provide a complimentary tool to inform experimental design without the cost and complexity of live animal studies. A morphologically variable virtual population (N = 10) of NHPs quantified the interaction of morphological variability and different impact conditions in a unilateral cervical contusion, including impactor size (4 and 5 mm) and mediolateral alignment over the cord midline (0.5 and 1 mm). We explored the effect of these conditions on the magnitude and intersubject variability of impact force and cord lateral slippage. The study demonstrated that a 1-mm mediolateral alignment maximized peak forces and minimized lateral slippage. A 5-mm impactor was beneficial in increasing peak forces, whereas a 4-mm impactor reduced lateral slippage. Comparatively, intersubject variability in peak forces and lateral slippage were minimized with a 0.5-mm mediolateral alignment. The study highlights that impact parameters selected based on peak forces may not be beneficial in reducing variability. The study also showed that morphology was an important contributor to variability. Integrating morphology variability through a virtual population in an injury simulation to investigate mechanistic research questions will more effectively capture the heterogeneity of experiments and provide better insights for effective experimental design.