We describe a neuro-optical microfluidic platform for studying injury and subsequent regeneration of individual mammalian axons. This platform consists of three components integrated on an inverted microscope, which include a compartmentalized neuronal culture microfluidic device, a femtosecond laser to enable precise axotomy, and a custom built mini cell culture incubator for continuous long term observation of post injury events. We demonstrate the unique capabilities of the platform by injuring individual central and peripheral nervous system axons and monitoring the post injury sequence of events from initial degeneration to subsequent regeneration. This platform will enable study and understanding of neuronal response to injury that is currently not possible with conventional cell culture platform and tools.
This purpose of this study was to replicate foot-ankle injuries seen in the military and derive human injury probability curves using the human cadaver model. Lower legs were isolated below knee from seventeen unembalmed human cadavers and they were aligned in a 90-90 posture (plantar surface orthogonal to leg). The specimens were loaded along the tibia axis by applying short-time duration pulses, using a repeated testing protocol. Injuries were documented using pre- and post-test X-rays, computed tomography scans, and dissection. Peak force-based risk curves were derived using survival analysis and accounted for data censoring. Fractures were grouped into all foot-ankle (A), any calcaneus (B), and any tibia injuries (C), respectively. Calcaneus and/or distal tibia/pilon fractures occurred in fourteen tests. Axial forces were the greatest and least for groups C and B, respectively. Times attainments of forces for all groups were within ten milliseconds. The Weibull function was the optimal probability distribution for all groups. Age was significant (p < 0.05) for groups A and C. Survival analysis-based probability curves were derived for all groups. Data are given in the body of paper. Age-based, risk-specific, and continuous distribution probability curves/responses guide in the creation of an injury assessment capability for military blast environments.
For compression-related injuries, specimen age should be used as a covariate or individual specimen data may be prescaled to derive risk curves. For distraction- or extension-related injuries, however, specimen age need not be used as a covariate in the statistical analysis. The findings from these tests and survival analysis indicate that the age factor modulates human cervical spine tolerance to impact injury.
Quantification of biomechanical tolerance is necessary for injury prediction and protection of vehicular occupants. This study experimentally quantified lumbar spine axial tolerance during accelerative environments simulating a variety of military and civilian scenarios. Intact human lumbar spines (T12-L5) were dynamically loaded using a custom-built drop tower. Twenty-three specimens were tested at sub-failure and failure levels consisting of peak axial forces between 2.6 and 7.9 kN and corresponding peak accelerations between 7 and 57 g. Military aircraft ejection and helicopter crashes fall within these high axial acceleration ranges. Testing was stopped following injury detection. Both peak force and acceleration were significant (p < 0.0001) injury predictors. Injury probability curves using parametric survival analysis were created for peak acceleration and peak force. Fifty-percent probability of injury (95%CI) for force and acceleration were 4.5 (3.9-5.2 kN), and 16 (13-19 g). A majority of injuries affected the L1 spinal level. Peak axial forces and accelerations were greater for specimens that sustained multiple injuries or injuries at L2-L5 spinal levels. In general, force-based tolerance was consistent with previous shorter-segment lumbar spine testing (3-5 vertebrae), although studies incorporating isolated vertebral bodies reported higher tolerance attributable to a different injury mechanism involving structural failure of the cortical shell. This study identified novel outcomes with regard to injury patterns, wherein more violent exposures produced more injuries in the caudal lumbar spine. This caudal migration was likely attributable to increased injury tolerance at lower lumbar spinal levels and a faster inertial mass recruitment process for high rate load application. Published 2017. This article is a U.S. Government work and is in the public domain in the USA. J Orthop Res 36:1747-1756, 2018.
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