Polyethylene Glycol Microgel-Based Magnetically Templated Hydrogel Scaffolds with 3D Aligned Microchannels for Nerve Repair

Hydrogels are promising materials for tissue repair applications mainly due to their high-water content and tunability for promoting cell growth. Our lab is attempting to develop a degradable polyethylene glycol (PEG)-based hydrogel scaffold with microchannels that mimic the properties of nerve tissue and can be used as a scaffold for nerve cell growth. Previously, our group has fabricated magnetically templated hydrogels using a combination of natural polymers. Hyaluronic acid and collagen have been used as the bulk hydrogel for magnetic alginate microparticles (MAMs) as the sacrificial template for microchannels. Although results hinted at the capability of the magnetic templating technique, the hydrogel possessed limited biodegradability and had channels spanning only a few millimeters. Thus, we sought to develop a scaffold with controllable degradability and reduced pre-hydrogel solution viscosity to enable better MAM alignment.

Initially we introduced polyethylene glycol-diacrylate (PEG-da) microgels in a pre-hydrogel solution to achieve an optimum yield stress for holding MAMs in place. Pre-hydrogels were first placed in a magnetic field to align the MAMs, creating columns of microparticles in solution. The hydrogels were then fabricated by UV polymerization of polyethylene glycol-norbornene and polyethylene glycol-dithiol (PEG-DT) through thiol-ene click chemistry in the presence of aligned MAMs. Once the UV initiated cross-link occurred, the hydrogels were placed in an ethylenediaminetetraacetic acid solution to remove remaining MAMs, leaving behind microchannels for cell migration. Optimum conditions to support alignment corresponded to 5% w/v microgels, however MAM clearance from these hydrogels was poor compared to our previous hydrogel composition. We hypothesized that this reduced clearance rate is due to excess polymer needed to crosslink around MAMs and PEG-da microgels.

To address slow MAM clearance, the project has turned towards the creation of a hydrogel through a photocrosslinked system of microgels formed via extrusion fragmentation. Polyethylene glycol-norbornene and PEG-DT undergo UV polymerization in a syringe to form a bulk hydrogel before extrusion through successively smaller needles to form irregularly shaped microgels. These microgels contain excess functional groups that can undergo a secondary cross-link to form a complete hydrogel. MAMs are inserted in a microgel solution, aligned, and degraded as before, generating channels for cell growth. Finally, mechanical testing of the hydrogels will be performed to ensure they mimic the mechanical properties of nerve tissue before in vitro studies are performed and channel imaging will be performed with fluorescent dyes to quantify length.