Magneto-Responsive Silk Microfibers for Neuroregeneration

Magneto-responsive fiber-based architectures represent an exciting prospect in the development of hierarchically ordered tissue engineering scaffolds, facilitating non-invasive, in situ spatiotemporal manipulation and organization of regenerative cues via an externally applied magnetic field. [1] While magneto-responsive fiber architectures are typically fabricated from magnetic nanoparticle (MNP)-doped polymeric solutions, risks of MNP leaching and subsequent cytotoxic intracellular accumulation remain unaddressed. To this end, chelation of paramagnetic ferric iron ions (Fe³⁺) is a promising alternative to MNP-doping. [2] Given its innately fibrous structure, notable capacity for heavy metal chelation, and FDA-approval as a biocompatible, biodegradable, naturally derived biomaterial [3, 4], silk fibroin extracted from <i>Bombyx mori</i> silkworm cocoons offers a unique, unexplored opportunity to fabricate MNP-free magneto-responsive fiber architectures. In this work, passive chelation of ferric iron is explored as an MNP-free alternative in the magnetic functionalization of silk-based biomaterials. Silk fibroin microfibers (mSF) treated with aqueous ferric chloride (FeCl₃) exhibit significantly increased iron content relative to the nascent protein as determined by x-ray photoelectron spectroscopy (XPS). Coupled with the absence of detectable chlorine traces and iron oxide species, the predominantly ferric oxidation state of iron within FeCl₃-treated mSF (Fe³⁺-mSF) suggest incorporation of iron, without reduction, at innate oxygen-containing ligands of mSF. On exposure to an external magnetic field, Fe³⁺-mSF displays paramagnetic magnetization behaviors that facilitate field-parallel alignment. Both magnetization and directional uniformity increased concomitantly with iron exposure during FeCl₃ treatment, suggesting the observed magnetic response of Fe³⁺-mSF is derived from the chelated iron. In vitro biocompatibility of the Fe³⁺-mSF has been confirmed using human dermal fibroblasts and neuroprogenitor cells (NPCs). This work is the first to investigate the magneto-responsive properties and biocompatibility of ferric iron chelated SF, demonstrating a novel, MNP-free alternative approach to magnetic functionalization of TE scaffolds. Ongoing work is underway to evaluate NPC alignment and axonal growth, differentiation, and function in response to the aligned guidance architecture.<br/><br/><b>References: </b>1. Adedoyin AA. <i>Nano Res</i>. 2018;11, 2. Marasini R. <i>RSC Adv</i>. 2021;11, 3. Holland C. <i>Adv Healthcare Mater</i>. 2019;8, 4. Pilley S. <i>Environ Sci Pollut Res</i>, 2022