Magnetic Nanofibrous Hydrogels for Dynamic Control of Stem Cell Differentiation

The extracellular matrix in tissue consists of complex heterogeneous soft materials with hierarchical structure and dynamic mechanical properties dictating cell and tissue level function. In many natural matrices, there are nanofibrous structures that serve to guide cell activity and dictate the form and function of tissue. Synthetic hydrogels with integrated nanofibers can mimic the structural properties of native tissue; however, model systems with dynamic mechanical properties remain elusive. Here we demonstrate modular nanofibrous hydrogels that can be reversibly stiffened in response to applied magnetic fields. Iron oxide nanoparticles were incorporated into gelatin nanofibers through electrospinning, followed by chemical stabilization and fragmentation. These magnetoactive nanofibers can be mixed with virtually any hydrogel material and reversibly stiffen the matrix at a low fiber content (≤3%). In contrast to previous work, where a large quantity of magnetic material disallowed cell encapsulation, the low nanofiber content allows matrix stiffening with cells in 3D. Using adipose derived stem cells, we show how nanofibrous matrices are beneficial for both osteogenesis and adipogenesis, where stiffening the hydrogel with applied magnetic fields enhances osteogenesis while discouraging adipogenesis. Skeletal myoblast progenitors were used as a model of tissue morphogenesis with matrix stiffening augmenting myogenesis and multinucleated myotube formation. The ability to reversibly stiffen fibrous hydrogels through magnetic stimulation provides a useful tool for studying nanotopography and dynamic mechanics in cell culture, with a scope for stimuli responsive materials for tissue engineering.