Tuning hydrogel properties and Schwann cell behavior through microchannel size control in magnetically templated hydrogels

Abstract

Peripheral nerve injury is a common condition and the development of materials that enhance Schwann cell migration to aid in regeneration is critical as the body has a limited ability to repair transected nerves. While various techniques have introduced 2D and 3D physical cues in biomaterials to promote Schwann cell infiltration, developing cell-scale tubular channels (<50 µm in diameter) with disease relevant lengths and high areal densities (>100 channels per mm²) remains an area of active interest. Here, we utilized a patterning technique called magnetic templating that utilizes size-tunable sacrificial magnetic porogens to form aligned microporous structures in of varying diameters inside hydrogels. The role of microstructure size on hydrogel physical properties and the influence of channel size on hydrogel mechanics and Schwann cell behavior was evaluated. Microchannel morphology, assessed by fluorescence microscopy, closely followed the structure of the sacrificial porogen chains, visualized via nano computed tomography. Porogens cleared within 7 days and their size had a minor influence on the mechanical properties. Smaller porogens led to higher areal channel densities but resulted in shorter channel lengths. Lastly, in vitro experiments suggest Schwann cells organized into tubular structures within smaller diameter channels but displayed mixed morphologies (stretched, clumped, round) in the larger channels. This work demonstrates that magnetic templating enables formulation of hydrogels with aligned microchannels of tunable size with the potential to guide cellular organization.