Xanthan Gum–Iron System: Natural, Mechanically Tunable, Bioactive, and Magnetic-Responsive Hydrogels for Biomedical Engineering Applications

Xanthan gum (XG) has performed far better than other polysaccharides for industrial purposes, e.g., food, pharmaceutical, and cosmetic applications, due to its outstanding thickening effect, pseudoplastic rheological properties, and non-toxicity. However, there is no crosslinking strategy available for non-modified XG that allows its sole use within cells for biomedical engineering applications. Here, we established this crosslinking strategy while processing it via additive manufacturing techniques. The suitability of divalent (Ca²⁺, Mg²⁺, and Fe²⁺) and trivalent (Al³⁺ and Fe³⁺) ions was evaluated by an in situ rheological assessment. Fe³⁺ demonstrated a high affinity to XG by forming a stable crosslinking effect, and the baseline XG-Fe³⁺ hydrogel exhibited outstanding printability and high culture stability (60 days). Although XG-Fe³⁺ demonstrated high biocompatibility for hMSCs with sustained cytocompatible iron release, these cell-laden constructs are inert. Envisioning biological functionality, we blended human methacryloyl platelet lysates (hPLMA) with XG-Fe³⁺ and either used inert XG-Fe³⁺ or bioactive cell-adhesive XG-Fe³⁺-PLMA, resulting in a 10-fold increase in strength compared to non-crosslinked XG. Remarkably, whether inert or bioactive, hydrogels proved to be mechanically tunable (from ∼3 to 203 kPa), ideal for tissue engineering applications. Later, we expanded the XG-Fe³⁺ role to a delivery system using magnetic nanoparticles (MNPs), and magnetically responsive scaffolds were obtained (XG-Fe³⁺-MNP). Finally, to explore the convergence of 3D printing and melt electrowriting (MEW), polycaprolactone (PCL) was included to obtain hybrid scaffolds (XG-PLMA-PCL). Our findings present a novel XG-Fe³⁺ hydrogel with remarkable versatility as a natural, mechanically tunable, bioactive, and magnetic- responsive system for sole or hybrid use. This unusual set of capabilities meets the current demand for developing tailored hydrogels for complex biomedical engineering applications.