On-Demand Magnetically-Activated Drug Delivery from Additively Manufactured Porous Bone Implants to Tackle Antibiotic-Resistant Infections

This study proposes a new concept for an on-demand drug releasing device intended for integration into additively manufactured (i.e., 3D printed) orthopedic implants. The system comprises a surface with conduits connected to a subsurface reservoir used for storage and on-demand release of antimicrobial agents, covered with a cap that prevents the antibacterial agents from being released until alternating magnetic field (AMF) raises the temperature of the cap, thus, releasing the stored drug. To demonstrate this concept, Ti6Al4V specimens are directly 3D printed using selective laser melting and their surface, reservoirs, and drug releasing properties are characterized. A new synthetic antimicrobial peptide, SAAP-148, is thereafter tested for its cytotoxic, osteogenic, and immunomodulatory effects at concentrations relevant for its minimal bactericidal concentration (MBC) and is compared with its natural analogue, LL-37. The results showed that AMF successfully activated the release from the 3D printed loaded samples. Both peptides demonstrated to be non-cytotoxic within the MBC levels for macrophages and preosteoblasts and did not influence their osteoimmunomodulatory behavior. The findings of this study indicate that the proposed concept is technically feasible and has the potential to be used for the development of bone implants with on-demand delivery systems to fight IAI without systemic or continuous local release of antibiotics.