PCL/Sodium-Alginate Based 3D-Printed Dual Drug Delivery System with Antibacterial Activity for Osteomyelitis Therapy

Chronic osteomyelitis is mostly caused by bacteria such as S. aureus, and is often treated with oral antibiotics or injections to suppress the bacteria. In severe cases, however, surgical treatment using antibiotic beads and metal supports may be required. In these surgeries, bacterial attachment to the metal may lead to biofilm formation and reduce antibiotics' penetration to the bacteria. Reoperation must be performed to prevent bacterial inflammatory reactions and antibiotic resistance. Thus, in this study, we developed a dual-drug-releasing PCL/sodium-alginate-based 3D-printed scaffold to effectively treat osteomyelitis by removing the biofilm. We proposed an antibiotic-loaded biodegradable polymer scaffold using 3D printing, which was encapsulated by a second antibiotic-containing hydrogel. Then, we successfully established a dual-drug-based scaffold that consisted of a cefazolin (CFZ)-containing polycaprolactone 3D scaffold and a rifampicin (RFP)-loaded alginate hydrogel encapsulating the 3D scaffold. Our scaffold showed a synergistic effect, whereby biofilm formation was inhibited by RFP, which is an external drug, and bacterial activity was inhibited by CFZ, which is an internal drug that increases antibacterial activity. We also confirmed that the dual-drug-based scaffold did not affect the proliferation of human osteoblasts. Our findings suggest that this dual drug delivery system may serve as a new therapeutic treatment for osteomyelitis that overcomes the limitations of individual drugs.