Magnetic particle templating of hydrogels: engineering naturally derived hydrogel scaffolds with 3D aligned microarchitecture for nerve repair

Objective. Hydrogel scaffolds hold promise for a myriad of tissue engineering applications, but often lack tissue-mimetic architecture. Therefore, in this work, we sought to develop a new technology for the incorporation of aligned tubular architecture within hydrogel scaffolds engineered from the bottom-up. Approach. We report a platform fabrication technology-magnetic templating-distinct from other approaches in that it uses dissolvable magnetic alginate microparticles (MAMs) to form aligned columnar structures under an applied magnetic field. Removal of the MAMs yields scaffolds with aligned tubular microarchitecture that can promote cell remodeling for a variety of applications. This approach affords control of microstructure diameter and biological modification for advanced applications. Here, we sought to replicate the microarchitecture of the native nerve basal lamina using magnetic templating of hydrogels composed of glycidyl methacrylate hyaluronic acid and collagen I. Main results. Magnetically templated hydrogels were characterized for particle alignment and micro-porosity. Overall MAM removal efficacy was verified by 96.8% removal of iron oxide nanoparticles. Compressive mechanical properties were well-matched to peripheral nerve tissue at 0.93 kPa and 1.29 kPa, respectively. In vitro, templated hydrogels exhibited approximately 36% faster degradation over 12 h, and were found to guide axon extension from dorsal root ganglia. Finally, in a pilot in vivo study utilizing a 10 mm rat sciatic nerve defect model, magnetically templated hydrogels demonstrated promising results with qualitatively increased remodeling and axon regeneration compared to non-templated controls. Significance. This simple and scalable technology has the flexibility to control tubular microstructure over long length scales, and thus the potential to meet the need for engineered scaffolds for tissue regeneration, including nerve guidance scaffolds.