Biocompatibility of Additively Manufactured Fe-AZ31 Biodegradable Composites for Craniofacial Implant Applications

Metallic plating systems composed of titanium and its alloys remain the standard treatment for craniofacial bony fixation but may require secondary removal due to infection, implant migration, or discomfort. Thus, biodegradable metallic implants may eliminate complications and secondary procedures while maintaining structural integrity. Our previous work demonstrated the fabrication of immiscible Fe-AZ31 composites via additive manufacturing with improved degradation kinetics over pure Iron. This study aimed to evaluate the in vitro and in vivo biocompatibility of Fe-AZ31 composites for potential craniofacial fixation applications. Pure iron (Fe), Mg alloy (AZ31) and Fe-AZ31 samples were fabricated for extract-based cytotoxicity testing using HFF-1 fibroblasts, L929 fibroblasts and hFOB osteoblasts. Metal extracts were prepared at a 3 cm^2/mL surface-to-volume ratio in complete media at 37C and cell viability was measured by live/dead assay after 24 and 72h exposure. For in vivo evaluation, Fe-AZ31, Fe, and Ti plates were implanted subcutaneously in wild type mice for 6 weeks, 3 and 6 months. Implant degradation, histologic response, hematology, and serum biochemistry were assessed. Fe-AZ31 extracts demonstrated >70% cell viability across all cell types at both timepoints with normal cell morphology and adhesion, whereas AZ31 extracts caused marked cytotoxicity associated with pronounced alkalization (pH 10). In vivo, Fe-AZ31 implants exhibited gradual surface corrosion accompanied by mild, transient inflammation and minimal capsule formation over time. No systemic toxicity was observed. Hematology and serum biochemistry remained within physiological limits. Additively manufactured Fe-AZ31 composites demonstrate acceptable biocompatibility and favorable tissue responses, supporting their development as resorbable metallic fixation devices for craniofacial reconstruction.