Engineering three-dimensional (3D) cell-dense tissues with a well-organized structure remains a challenge in tissue engineering. In this study, highly oriented fibrous bundles, consisted of composite fibers of poly(L-lactide-co- glycolide)/superparamagnetic iron oxide nanoparticles, were fabricated using an electrospinning technique. The magnetic properties of the fabricated fibrous bundles were examined by a vibrating sample magnetometer and a superconducting quantum interference device; the results demonstrate that the fabricated fibrous bundles revealed superparamagnetic behavior without magnetic hysteresis. After seeding C2C12 myoblasts on the fibrous bundles, cells were grown along the direction of the underlying fibers (cell rods), an aligned pattern similar to those in native skeletal muscle tissues. When treated with the differentiation medium, myoblasts were fused together and formed multinucleated myotubes. As soon as applying an external magnetic field, the cell rods can spontaneously response to the magnetic control and self-assemble into 3D tissues with a highly ordered architecture. These findings demonstrate that the magnetically susceptible fibrous bundles not only can serve as a functional unit providing the topographic cue for cell orientation, but also can be magnetically manipulated for the creation of 3D cell-dense constructs. This technique may be applied to various cell types and scaffold configurations, thus advancing the design of engineered tissues that more closely replicate native tissues.
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