A Computational Model for Investigating the Effects of Strain on Axonal Injuries in a Microfluidic Cell Culture Platform

Background and Aim: Traumatic brain injury and spinal cord injury aredebilitating causes of traumatic death and disability worldwide. Inertialforces that occur during acceleration/deceleration of the brain can leadto the generation of forces exerted on axons causing axons to be injured.Reliable and accurate models that can simulate an applied injury need tobe developed. These models must be capable of applying physiologicallevels of injury and assessing the extent of the injury. Here, we focus onmodels that include stretch injuries. A finite element model was used toprovide quantitative measures for mechanical changes and their effectson the function of the axon.Methods: Our study models an axon in cell culture platform using athree-dimensional geometry (based on experimental works) for axon andplatform, a uniaxial strain device as an injury platform in a finite elementanalysis. By using a microfluidic device like a cell culture environment,we can distinguish and observe a single axon. In order to accuratelypredict the strain applied to an axon, a 2nd order Ogden hyperelasticmodel is used for describing PDMS. A pneumatic pressure is appliedto the cavity under the microchannel layer to produce a uniaxial strainin the axon. Different injected volumes and rate of injection producemagnitudes of strain (11%, 25%, and 42%) and strain rate (260 ms-1, 50ms-1, and 22 ms-1). To assume proper mechanical properties of the axon,we use data from in vivo experiments and results from mathematicalmodels. In order to observe the effects of the fluid in microchannel onthe axon, an FSI model was used. We describe the whole axon as asolid hyperelastic cylinder with an approximate radius of 1.5 μm. Thecommercial finite element software, COMSOL Multiphysics 5.2, is usedfor the simulation.Results: The results from the FSI models showed no significant effect fromfluid on the mechanical response of the axon (strain value was equal to9.33e-3%), thus we did not include this in our future considerations. Itwas shown that the role of flow on the microchannels is just to provide aproper environment for the axon to grow. Results have shown that in highstrain and strain rate values as to be equal to 42% and 22 ms-1, we seethat injury occurs. The model showed a limit for the strain that will causeinjuries in the axon. It is also showed that the rate of strain has also agreat role in causing injuries. Breaking microtubule of axon has the mostimportant role in injuries, due to this reason that mechanical integrity ofaxon comes from microtubule bundlesConclusion: This study aimed to show a basic model for axon and inspectits mechanicals behavior as a basis for future works in regenerativemedicine. There are several important factors (e.g., strain, the rate of strain, axon structure and mechanical properties and the effect ofcell culture fluid in the microchannel) that have been discussed. Thismechanical model can be coupled with a chemical or electrochemicalmodel in order to obtain greater clinical relevance.

Keywords:

Biomechanics , Cell mechanics , Traumatic brain injury , Axon , Strain