Drug-eluting biodegradable metals and metal-ceramic composites: High strength and delayed drug release

Abstract

Biodegradable metals emerged as promising temporary bone implants. The integration of additional features such as local drug delivery (LDD) can also support their osteointegration, promote bone regeneration, and prevent biomaterial-centered infections that are difficult to treat. LDD is achieved by drug-eluting coatings or porous implants where the drug is impregnated after implant fabrication because the high temperatures used during conventional production processes would result in their thermal decomposition. We produced biodegradable iron (Fe)-based vancomycin (VH)-eluting metals and metal-ceramic composites by a simple high-pressure consolidation/cold sintering (CS) process at room temperature that display high mechanical strength and antibacterial activity. Aiming to expand the application of this production method and shed light into the drug loading and release mechanisms in this type of biomaterials, this work reports on the production and characterization of VH-loaded Fe and Fe-iron oxide (Fe2O3) composites (Fe-Fe2O3). We use focus ion beam milling for the first time to investigate the drug-metal interface and investigate the mechanical and degradation properties of VH-free and VH-loaded Fe and Fe-Fe2O3. Results show very high mechanical strength of drug-eluting Fe and Fe-Fe2O3 composites (up to than 780 MPa under compression, exceeding the maximum strength of cancellous bone more than three times) accompanied by a delayed drug release. Then, we confirm the good antimicrobial activity against Staphylococcus aureus and cell compatibility with the murine embryonic fibroblast cell line NIH/3T3 in vitro. Overall results confirm the promise of drug-eluting metals and metal-ceramic composites for LDD in bone.