Magnetic Nanocomposite Hydrogels for Directing Myofibroblast Activity in Adipose‐Derived Stem Cells

Intrinsic and extrinsic mechanical forces influence the growth, morphogenesis, and differentiation of cells during development. As development progresses, interactions between cells and the extracellular matrix (ECM) guide lineage determination by transmitting forces from cell-matrix engagement through focal adhesions, into the cytoplasm, and to the nuclear membrane to directly and indirectly dictate gene expression programs. Researchers have developed a host of dynamic synthetic materials with controllable properties to study how matrix mechanics influence cell behavior. The stiffness of engineered ECM materials have been modulated through either crosslinking density or using external stimuli such as light, temperature, pH, ionic additives, ultrasound and magnetic force. Although these approaches have shown great success in changing matrix properties as well as influencing cell activity, complex chemical modification are invariably necessary, which obviates the ease of translation to diverse laboratory settings. Cell size and morphology are influenced by matrix stiffness. On a stiff surface, cells can adopt robust focal adhesions with an organized cytoskeleton, thereby facilitating a dynamic push and pull, whereas on soft surface, cells fail to develop this contractile network. In addition to cell morphology, stiffness also influences cellular functions such a proliferation and differentiation. An important contractile cell type for tissue engineering is the myofibroblast, which will show diverse adhesive characteristics on stiff and soft substratum. Human mesenchymal stem cells (MSCs) are a promising cell source for vascular tissue engineering, as these fibroblastic stromal cells readily express smooth-muscle actin and can undergo myofibroblast differentiation. MSC lineage specification can be influenced by biochemical and biophysical properties such as substrate stiffness, cell geometry, and matrix protein composition. Furthermore, MSCs show multiple differentiation capacities such as differentiating into myofibroblasts via direct treatment with soluble factors or by mechanical stimulation of the substrate. In this article, we present a simple approach to influence myofibroblast differentiation by incorporating magnetic nanoparticles into hydrogels, where attenuation of a magnetic field leads to substrate stiffening. Nanoscale Fe3O4 was fabricated through a chemical coprecipitation method and polymerized directly within poly(ethylene glycol) dimethacrylate (PEGDM) hydrogels. The physicochemical properties of the nanoparticles and the hydrogel network architecture enabled particle retention within the material. Average cell area changes with the presence of a magnetic field leads to an increase in the fraction of cultured MSCs displaying a myofibroblast phenotype. M. S. Islam, T. G. Molley, Prof. K. A. Kilian School of Materials Science and Engineering The University of New South Wales Sydney, NSW 2052, Australia E-mail: k.kilian@unsw.edu. au J. Ireland, Prof. K. A. Kilian School of Chemistry Australian Centre for Nanomedicine The University of New South Wales Sydney, NSW 2052, Australia Prof. J. J. Kruzic School of Mechanical and Manufacturing Engineering The University of New South Wales Sydney, NSW 2052, Australia