Fiber Stretch and Reorientation Modulates Mesenchymal Stem Cell Morphology and Fibrous Gene Expression on Oriented Nanofibrous Microenvironments
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Because differentiation of mesenchymal stem cells (MSCs) is enacted through the integration of soluble signaling factors and physical cues, including substrate architecture and exogenous mechanical stimulation, it is important to understand how micropatterned biomaterials may be optimized to enhance differentiation for the formation of functional soft tissues. In this work, macroscopic strain applied to MSCs in an aligned nanofibrous microenvironment elicited cellular and nuclear deformations that varied depending on scaffold orientation. Reorientation of aligned, oriented MSCs corresponded at the microscopic scale with the affine approximation of their deformation based on macroscopic strains. Moreover, deformations at the subcellular scale corresponded with scaffold orientation, with changes in nuclear shape depending on the direction of substrate alignment. Notably, these deformations induced changes in gene expression that were also dependent on scaffold and cell orientations. These findings demonstrate that directional biases in substrate microstructure convey direction-dependent mechanosensitivity to MSCs and provide an experimental framework in which to explore the mechanistic underpinnings of this response.
KeywordsMechanobiology Electrospinning Biomaterials Microenvironment
This work was supported with funding from the National Institutes of Health (R01 EB02425, R01 AR056624), the Penn Center for Musculoskeletal Disorders, and the Human Frontiers in Science Program.
- 13.Driscoll, T. D., N. L. Nerurkar, N. T. Jacobs, D. M. Elliott, and R. L. Mauck. Shear mechanics of electrospun scaffold for annulus fibrosus tissue engineering. J. Mech. Behav. Biomed. Mater. (in press).Google Scholar
- 27.Mow, V. C., and R. Huiskes. Basic Orthopaedic Biomechanics and Mechanobiology. Philadelphia, PA: Lippincott Williams & Wilkins, 1991.Google Scholar
- 32.Nerurkar, N. L., R. L. Mauck, and D. M. Elliott. Modeling interlamellar interactions in angle-ply biologic laminates for annulus fibrosus tissue engineering. Biomech. Model Mechanobiol. doi: 10.1007/s10237-011-0288-0, 2011.
- 34.Nesti, L. J., W. J. Li, R. M. Shanti, Y. J. Jiang, W. Jackson, B. A. Freedman, T. R. Kuklo, J. R. Giuliani, and R. S. Tuan. Intervertebral disc tissue engineering using a novel hyaluronic acid-nanofibrous scaffold (HANFS) amalgam. Tissue Eng. Part A 14(9):1527–1537, 2008.PubMedCrossRefGoogle Scholar