Iron‐Chelated Silk Microfibers as a Novel Magneto‐Responsive Architecture for In Situ Aligning Biomaterial Scaffolds

Abstract Magnetically functionalized biomaterials represent an exciting prospect in the development of stimuli‐responsive tissue engineering scaffolds. Magneto‐responsive properties are traditionally imparted to scaffold systems via integration of iron oxide‐based magnetic nanoparticles (MNPs), yet poor understanding of long‐term MNP toxicity presents a significant translational challenge. Given the demonstrated iron‐binding capacity of silk fibroin (SF), passive chelation of ferric iron ions is explored herein as an alternative, MNP‐free approach for magnetic functionalization of silk fibroin (SF)‐based biomaterials. SF microfibers treated with aqueous ferric chloride (FeCl 3 ) exhibit significantly increased iron content relative to the nascent protein. Coupled with the absence of detectable chlorine traces and inorganic iron oxide species, the ferric oxidation state of the iron detected within the FeCl 3 ‐treated microfibers suggests that iron is incorporated, without reduction, at innate oxygen‐containing ligands in SF. On exposure to an external magnetic field, these ferric iron‐chelated SF microfibers (Fe 3+ ‐mSF) display paramagnetic magnetization behaviors that facilitate field‐parallel alignment. Both magnetization and directional uniformity increase with iron exposure during FeCl 3 treatment, suggesting the observed magnetic response of Fe 3+ ‐mSF is derived from the chelated iron. This work is the first to investigate the magneto‐responsive properties and biocompatibility of ferric iron‐chelated SF, highlighting a novel, MNP‐free mechanism for synthesizing magnetically functionalizedscaffolds.