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.
Polymeric biomaterials exhibit excellent physicochemical characteristics as a scaffold for cell and tissue engineering applications. Chemical modification of the polymers has been the primary mode of functionalization to enhance biocompatibility and regulate cellular behaviors such as cell adhesion, proliferation, differentiation, and maturation. Due to the complexity of the in vivo cellular microenvironments, however, chemical functionalization alone is usually insufficient to develop functionally mature cells/tissues. Therefore, the multifunctional polymeric scaffolds that enable electrical, mechanical, and/or magnetic stimulation to the cells, have gained research interest in the past decade. Such multifunctional scaffolds are often combined with exogenous stimuli to further enhance the tissue and cell behaviors by dynamically controlling the microenvironments of the cells. Significantly improved cell proliferation and differentiation, as well as tissue functionalities, are frequently observed by applying extrinsic physical stimuli on functional polymeric scaffold systems. In this regard, the present paper discusses the current state-of-the-art functionalized polymeric scaffolds, with an emphasis on electrospun fibers, that modulate the physical cell niche to direct cellular behaviors and subsequent functional tissue development. We will also highlight the incorporation of the extrinsic stimuli to augment or activate the functionalized polymeric scaffold system to dynamically stimulate the cells.
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