Human Fibroblast Migration in Three-Dimensional Collagen Gel in Response to Noninvasive Electrical Stimulus. I. Characterization of Induced Three-Dimensional Cell Movement

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Abstract
Cell adhesion and motility is one of the important biological processes involved in cell growth, differentiation, inflammatory response, and wound healing, and in engineered tissue constructs. Because cellular behaviors can be influenced by the local electrical environment within tissues, induced cell orientation, adhesion, and migration by exogenous electrical stimulus have been extensively examined on two-dimensional (2D) substrates. Similar cellular responses in 3D matrix have not been well documented, however. We have therefore used the 3D collagen gel as a model to characterize human fibroblast movement in response to noninvasive DC electrical stimulus. Cell movements were compared by plating the cells on 2D substrates and embedding them into the reconstituted 3D collagen gel. Our results indicate that 3D cell movement is regulated by both electrical stimulus strength and collagen concentration. For example, a small noninvasive electrical stimulus (0.1 V/cm) was found to be sufficient to induce 3D cell migration, and a collagen concentration of 0.58 mg/mL appeared to represent the optimal scaffold network environment. The same electrical stimulus did not induce significant 2D cell movement, however. Typical cell migration was best analyzed by assuming both directed and random movement and that, in response to an electrical stimulus of 0.1 V/cm, the cell migration rate was 0.23 µm/min and the random motility coefficient was 0.07 µm2/min. Because regulation of cell adhesion and migration is often desired in tissue engineering, the ability to apply physical stimulus and to control 3D cell movement may provide an alternative methodology for regulation of engineered tissue constructs.