Iron-Chelated Silk Microfiber/Hydrogel Composites as Injectable, Magnetically Aligned Cell Guidance Scaffolds

In the design of biomaterial scaffolds for traumatic spinal cord injury (SCI), anisotropic composites of magnetically aligning architectures and injectable hydrogels have garnered increasing interest for their combined neuroregenerative and neuroprotective advantages, uniquely supporting both axonal orientation cues and minimally invasive delivery. Herein, ferric iron-chelated silk fibroin microfibers (Fe³⁺-mSF) are explored as a magnetic nanoparticle-free alternative to existing magneto-responsive fiber architectures. Functionalization of nascent mSF via iron chelation exhibited stability at physiological pH, with minimal iron release observed over 7-d and 3-month periods. Mechanically, the addition of Fe³⁺-mSF to an existing injectable, in situ crosslinking hydrogel did not compromise its injectability, gelation kinetics, or low swelling profile. Fe³⁺-mSF cytocompatibility was observed in SH-SY5Y cells (neuronal analog), both when cultured with Fe³⁺-mSF-supplemented media and when cultured within Fe³⁺-mSF/collagen hydrogels, and the addition of Fe³⁺-mSF to a collagen-only hydrogel resulted in a few significant changes in neuroregenerative biomarker expression. Finally, in a proof-of-principle study, magnetically-actuated alignment of Fe³⁺-mSF/hydrogel composites was achieved on the patient bed of a magnetic resonance imaging (MRI) machine, without obvious pulling of the fiber architecture from the hydrogel bulk. It is envisioned that this Fe³⁺-mSF-laden hydrogel system may be used as an injectable, in situ aligning neuroregenerative scaffold.