LAUSR

Next generation treatment strategies to treat the osteomyelitis with complete eradication of pathogen at the bone nidus and prevention of emergence of drug resistance is a real challenge in orthopaedics. Conventional treatments include long term adherence of patients to systemic antibiotic delivery, local delivery using non-degradable vehicles and surgical debridement are not completely effective in achieving successful results. In this study, a broad-spectrum antibiotic, rifampicin (RFP), was incorporated into a biphasic nanohydroxyapatite (nHAP)/calcium sulphate ceramic carrier (NC) system. In vivo release and distribution of rifampicin was evaluated for a period of one month by implanting NC and NC + RFP in subcutaneous pouch in rat model. We detected the RFP in bone and implanted NC scaffolds even after day 28 and the concentration was still higher than minimal inhibitory concentration of RFP when it was implanted with NC in abdominal subcutaneous pouch. Moreover, we also observed the accumulation of RFP in bone and NC when administered orally, showing strong binding between RFP and nHAP. Additionally, we generated an osteomyelitis bone infection model in rat tibia using Staphylococcus aureus as infective agent to evaluate the antibacterial and osteogenic efficiency of RFP containing NC as a delivery system. S aureus mediated implant infection is major problem in orthopaedics. The results suggested that NC loaded with RFP could eradicate the pathogen completely in bone nidus. Further, defect healing and bone formation was also evaluated by micro-CT and histological analysis demonstrating proper trabecular type bone formation at the debridement site and complete healing of the defect when NC + RFP was implanted. Our findings provide an insight into use of nHAP based ceramic matrix as a carrier of rifampicin to eradicate the bone infections and simultaneously promote the bone healing at the bone nidus.