Cellular Automaton and Finite Element Hybrid Simulation to Predict Axonal Extension Enhancement of Nerve Cell Under Mechanical Stimulation

Author(s):  
Shota Takeda ◽  
Yoshihiro Tomita ◽  
Eiji Nakamachi

In the clinical application, the mechanical stimulation against the damaged brain tissue is adopted as the kinesitherapy for the nerve regeneration. Nevertheless, the fundamental mechanism to repair the damaged nerve cell has not been revealed yet. Recently, the cyclic stretch stimulation has been reported as the efficacious treatment method to enhance the axonal extension for regenerative therapy of injured nerve cell. Therefore, we try to develop a new cellular automaton (CA) finite element (FE) hybrid method to predict the axonal extension and nerve network generation, which can evaluate the effect of stretch stimulation on the cell body, axon and dendrites. In the FE results, the stress concentration occurred at the junction of the axon and cell body. The maximum stress value in the axon was 8.2 kPa which is about twice as large as that of the cell body. CA adopted to predict the morphological evolution of nerve cells under the mechanical stimulation. It was confirmed that the stress affects to accelerate the axonal extension as experimentally suggested. As a result, our CAFE can be employed to simulate the axonal extension and generation of nerve network system under the condition of extra cellular mechanical stimulation.

Author(s):  
Kazuya Matsumoto ◽  
Yusuke Morita ◽  
Eiji Nakamachi

Recently, the electromagnetic and mechanical stimulation have been recognized as the effective extracellular environmental factor to enhance the defected peripheral nerve tissue regeneration. We designed and fabricated a bioreactor device, which can load the uniform AC magnetic field (ACMF) and the uniform tensile strain to stimulate PC12 nerve cell. For ACMF stimulation system, we used the pole piece structure to enable the uniform ACMF and in-situ microscopic observation. We confirmed the uniformity of magnetic field in the experiments. Further, the uniform strain in the stretch stimulation device was confirmed, even a slightly deviation from the designed strain was observed. It was a negligible small error. Next, we validated the effectiveness of PC12 axonal extension enhancement by two stimulation methodologies, ACMF and the cyclic stretch, under individual and combined stimulation conditions. ACMF showed a best enhancement effect on axonal extension, such as 70 μm at 96 h culture period, which rate is larger than the case of control. On the other hand, the stretch stimulation caused the exfoliation of cells. Hybrid stimulation succeeded to inhibit the exfoliation. However, the extensional rate was less than the case of ACMF. These results can be used to fabricate a bioreactor of nerve cell regeneration.


2014 ◽  
Vol 490-491 ◽  
pp. 867-871
Author(s):  
Guo Hui Wang ◽  
Wei Yi Chen

To understand the effect of mechanical stimulation on posterior sclera reinforcement (PSR), the rabbit scleral fibroblasts after PSR were subjected to stretch in vitro and MMP-2 and TIMP-2 expression of scleral fibroblasts were evaluated. Three-week-old rabbits were monocularly performed by eyelid suturation randomly to prepare experimental myopia eye. After 60 days, the experimental myopia eyes were treated by PSR. After 6 months, the posterior pole scleral fibroblasts (normal sclera - group A, sclera after operation - group B and fusion region of sclera and reinforcing band group C) were isolated and cultured in vitro. The cells were subjected to cyclic stretch regimens (sine wave, 3% and 6% elongation amplitude, 0.1Hz, 48h duration) by FX-4000 Tension System. The MMP-2 and TIMP-2 expression of scleral fibroblasts were evaluated by ELISA method. The results show that after cyclic stretch to the scleral fibroblasts of the normal sclera and the sclera after operation, the MMP-2 expression was significantly reduced and the TIMP-2 expression was significantly increased, the MMP-2 and TIMP-2 expression of the scleral fibroblasts of the fusion region after operation was no changed. It was indicated that the mechanical stimulation could regulate the MMP-2 and TIMP-2 expression of scleral fibroblasts and play an important role in the process of treating high myopia with PSR surgery.


2009 ◽  
Vol 131 (6) ◽  
Author(s):  
Omotunde M. Babalola ◽  
Lawrence J. Bonassar

While mechanical stimulation of cells seeded within scaffolds is widely thought to be beneficial, the amount of benefit observed is highly variable between experimental systems. Although studies have investigated specific experimental loading protocols thought to be advantageous for cartilage growth, less is known about the physical stimuli (e.g., pressures, velocities, and local strains) cells experience during these experiments. This study used results of a literature survey, which looked for patterns in the efficacy of mechanical stimulation of chondrocyte seeded scaffolds, to inform the modeling of spatial patterns of physical stimuli present in mechanically stimulated constructs. The literature survey revealed a large variation in conditions used in mechanical loading studies, with a peak to peak strain of 10% (i.e., the maximum amount of deformation experienced by the scaffold) at 1 Hz on agarose scaffolds being the most frequently studied parameters and scaffold. This loading frequency was then used as the basis for simulation in the finite element analyses. 2D axisymmetric finite element models of 2×4 mm2 scaffolds with 360 modulus/permeability combinations were constructed using COMSOLMULTIPHYSICS software. A time dependent coupled pore pressure/effective stress analysis was used to model fluid/solid interactions in the scaffolds upon loading. Loading was simulated using an impermeable frictionless loader on the top boundary with fluid and solid displacement confined to the radial axis. As expected, all scaffold materials exhibited classic poro-elastic behavior having pressurized cores with low fluid flow and edges with high radial fluid velocities. Under the simulation parameters of this study, PEG scaffolds had the highest pressure and radial fluid velocity but also the lowest shear stress and radial strain. Chitosan and KLD-12 simulated scaffold materials had the lowest radial strains and fluid velocities, with collagen scaffolds having the lowest pressures. Parametric analysis showed maximum peak pressures within the scaffold to be more dependent on scaffold modulus than on permeability and velocities to depend on both scaffold properties similarly. The dependence of radial strain on permeability or modulus was more complex; maximum strains occurred at lower permeabilities and moduli, and the lowest strain occurred at the stiffest most permeable scaffold. Shear stresses within all scaffolds were negligible. These results give insight into the large variations in metabolic response seen in studies involving mechanical stimulation of cell-seeded constructs, where the same loading conditions produce very different results due to the differences in material properties.


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