A Magneto-Responsive Hydrogel System for the Dynamic Mechano-Modulation of Stem Cell Niche

The biophysical microenvironment of cells dynamically evolves during embryonic development, leading to defined tissue specification. A versatile and highly adaptive magneto-responsive hydrogel system composed of magnetic nanorods (MNRs) and a stress-responsive polymeric matrix is developed to dynamically regulate the physical stem cell niche. The anisotropic magnetic/shape factor of nanorods is utilized to maximize the strains on the polymeric network, thus regulating the hydrogel modulus in a physiologically relevant range under a minimal magnitude of the applied magnetic fields below 4.5 mT. More significantly, the pre-alignment of MNRs induces greater collective strains on the polymeric network, resulting in a superior stiffening range, over a 500% increase as compared to that with randomly oriented nanorods. The pre-alignment of nanorods also enables a fast and reversible response under a magnetic field of the opposite polarity as well as spatially controlled heterogeneity of modulus within the hydrogel by applying anisotropic magnetic fields. The mechano-modulative capability of this system is validated by a mechanotransduction model with human-induced pluripotent stem cells where the locally controlled hydrogel modulus regulates the activation of mechano-sensitive signaling mediators and subsequent stem cell differentiation. Therefore, this magneto-responsive hydrogel system provides a platform to investigate various cellular behaviors under dynamic mechanical microenvironments.