Preparation and evaluation of microfluidic magnetic alginate microparticles for magnetically templated hydrogels

Our aim is to develop a hydrogel-based scaffold containing porous microchannels that mimic complex tissue microarchitecture and provide physical cues to guide cell growth for scalable, cost-effective tissue repair. These hydrogels are patterned through the novel process of magnetic templating where magnetic alginate microparticles (MAMs) are dispersed in a hydrogel precursor and aligned in a magnetic field before hydrogel crosslinking and subsequent MAM degradation, leaving behind an aligned, porous architecture. Here, a protocol for fabricating uniform MAMs using microfluidics was developed for improved reproducibility and tunability of templated microarchitecture. Through iron quantification, we find that this approach allows control over magnetic iron oxide loading of the MAMs. Using Brownian dynamics simulations and nano-computed tomography of templated hydrogels to examine MAM chain length and alignment, we find agreement between simulated and measured areal densities of MAM chains. Oscillatory rheology and stress relaxation experiments demonstrate that magnetically templated microchannels alter bulk hydrogel mechanical properties. Finally, in vitro studies where rat Schwann cells were cultured on templated hydrogels to model peripheral nerve injury repair demonstrate their propensity for providing cell guidance along the length of the channels. Our results show promise for a micro-structured biomaterial that could aid in tissue repair applications.