(335a) Tunable Three-Dimensional Microarchitecture in Magnetically Templated Hydrogels for Tissue Repair Applications

Tissue damage can occur due to traumatic injuries, congenital defects, or disease. While treatment options include autologous or donated tissue grafts, these options come with drawbacks: autologous grafts require multiple surgeries, making them invasive and costly while donated tissue can come with the possibility of immunogenic rejection and long waitlists. A popular strategy towards designing biomaterials for in situ tissue repair is through the inclusion of an organized, porous microarchitecture to: better mimic the organized structure of the extracellular matrix in functional tissues, provide physical guidance for proliferating cells, and improve transport of oxygen and nutrients throughout the scaffold. While there are many fabrication techniques in the literature for patterning materials with complex structure, there is a need for engineered strategies that are scalable, cost-effective, and applicable across different chemistries.

We have developed a novel method for patterning hydrogels with porous architecture: magnetic templating. This process involves dispersing magnetic alginate microparticles (MAMs) in a hydrogel precursor solution, aligning the MAMs in a uniform magnetic field, crosslinking the hydrogel around the MAM chains, and degrading the MAMs, leaving behind an anisotropic scaffold microarchitecture. The MAMs, which consist of magnetic iron oxide nanoparticles embedded in calcium-crosslinked alginate, are fabricated using a microfluidic flow-focusing system for high control over microparticle size and iron oxide loading, two parameters that are highly consequential in MAM chain assembly and the resulting microarchitecture of the templated channels.

Initial work has focused on hyaluronan-based hydrogels templated with 70 µm diameter channels. MAM chain assembly was characterized through nano-computed tomography scans of templated hydrogels and compared to Brownian dynamics simulations of MAM chain formation, finding quantitative agreement between the two in terms of areal density of MAM chains. Low vacuum scanning electron microscopy of templated hydrogels and confocal microscopy images of templated hydrogels backfilled with fluorescein isothiocyanate-dextran were used to confirm the porous nature of the templated channels. Mechanical properties of magnetically templated hydrogels were assessed through small angle oscillatory rheology and indentation, finding that the templating process and incorporation of porous channels lowers bulk mechanical properties. Finally, using peripheral nerve repair as a model application, we evaluated the templated hydrogels’ propensity for cellular infiltration through in vitro culture with rat Schwann cells.

We are currently conducting work to fabricate uniform MAMs of varying diameters, and thus elucidate the effect of MAM diameter on chain assembly/channel formation and importantly, cellular infiltration in vitro. This work will ultimately allow us to better understand what kinds of microarchitectures would be desirable for cellular infiltration and ultimately, for tissue repair applications.