만성 골수염 치료 및 골 결손의 재생을 위한 항생제 방출형 PCL/PLGA 인공지지체의 개발 및 이의 검증

Abstract

Osteomyelitis, which usually occurs by open fracture of bone or during orthopedic surgery, is a bone or bone marrow infection caused by bacteria. In most cases, if not properly treated with antibiotics in early stage, it progresses into chronic osteomyelitis. Once it becomes chronic state, it is hardly treated with intravenous antibiotics therapy because swollen bone marrow disturbs the blood flow through the blood vessels and capillaries in the infected site. In case of severe chronic osteomyelitis, debridement of necrotic bone and muscle tissue is necessary for preventing further infection. For treatment of chronic osteomyelitis after debridement, bone cement (PMMA) beads that contain antibiotics are implanted into the debrided space (or dead space) for delivering antibiotics locally to the infected site. However, due to its non-degradability, it should be removed after several weeks of implantation or it can generate immune rejection response. And additional surgery for bone grafting is necessary to regenerate the debrided bone and soft tissue. In this study, we have developed the biodegradable PCL/PLGA scaffold containing antibiotics for treatment of chronic osteomyelitis using multi-head deposition system (MHDS) which is one kind of rapid prototyping (RP) technology. Tobramycin, widely used in orthopedic field, is one of heat-stable aminoglycosides antibiotics. Polycaprolactone(PCL), poly lactic-co-glycolic acid(PLGA) and tobramycin were blended at high temperature of 120℃ and loaded into MHDS. And then various 3D shapes of tobramycin-loaded scaffolds were fabricated with layer by layer process. With these tobramycin-loaded scaffolds, we conducted in vitro and in vivo experiments for checking the anti-bacterial and anti-inflammatory effects of the scaffolds. And released tobramycin from the scaffold didn’t seem to lose its efficacy by heat-based fabrication.Based on the experimental results, we concluded that tobramycin-loaded scaffolds can be promising local drug delivery system for treatment of osteomyelitis, and they also have an effect on bone reconstruction of dead space.