3-D Cell Compression Device

3-D Cell Compression Device undeformed deformed

Trapezoidal Input

Trapezoidal Input

undeformed deformed

Fig. 5. In vitro injury devices for shear and compression injuries. Neural cells cultured in a 3-D configuration were subjected to either shear or compression injury with a prescribed strain magnitude and rate. This experimental model provides control over bulk material deformation, while local strains may vary due to cellular orientation within the matrix.

impact in these regions may make the cells more susceptible to death and/or dysfunction during the secondary phase of injury.

Although in vivo models can provide a more anatomically accurate representation of the structural and functional damage associated with human CNS injury, in vitro models allow for more thorough investigation of tissue tolerances because biomechanical insult parameters can be more precisely controlled and manipulated. In a recent study, the effects of both shear and compression modes of impact were investigated (Fig. 5). This is an example of how strain estimations derived from finite element analysis (FEA) can be applied to simplified culture environments to isolate components of the heterogeneous mechanical response (Fig. 6). Briefly, mixed cultures consisting of neurons and astrocytes were plated in a 3-D matrix and subjected to either shear or compressive loading (0.50 strain at strain rates of 1, 10, or 30s_1). Both types of loading resulted in significant increases in membrane permeability in a strain rate dependent manner, with no differences in the density or percentage of permeabilized cells based on mode of deformation. However, the degree of permeability marker uptake per permeabilized cell, potentially a gauge of local cellular strain/stress concentrations, was greater following shear deformation (Fig. 7). Interestingly, the density of dead cells was also significantly greater following shear deformation (5-7 fold increase) compared to compression (2-fold increase), suggesting that there is a correlation between the degree of membrane permeability and the extent of cell death. This study agrees with previous work demonstrating that shear deformation is the primary mode of tissue failure (Holbourn, 1943; Sahay et al., 1992).

Although this study evaluated cellular responses based on different modes of bulk deformation, local cellular strains are heterogeneous, and may be a function of cell orientation with respect to the bulk strain field (amongst other factors) (LaPlaca et al., 2005; Cullen and LaPlaca, 2006). We have demonstrated that neuronal response to loading depends on cell orientation, and hence local cellular strain, where maximal neurite loss occurred at shear-dominated strain regimes (LaPlaca et al., 2005). Ongoing in vitro studies are aimed at defining the biomechanical parameters (deformation mode, rate, and magnitude) that lead to structural

Finite element modeling of strain propagation following a focal insult (controlled cortical impact) in a rat.

in vivo simulations in vitro

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