A multi-barrier antibiotics loaded biodegradable composite bone cement for resolving chronic osteo-myelitis has been studied to understand the physico-mechanical properties,drug loading/eluting effi-ciency,and different merits and demerits prior to clinical application.After successful induction of bone infection in 28 rabbits using methicillin-resistant Staphylococcus aureus(MRSA)strains,calcium sulfate/bioactive glass based composite cement was implanted in 12 defects to assess its performance over parenteral therapy with microscopic and radiological examination for 90 days.The composite cement revealed acceptable physico-mechanical properties and controlled drug elution kinetics.Furthermore,the antibiotics concentrations in bone up to 42 days were sufficient to kill MRSA without eliciting adverse drug reactions.The striking feature of platelets aggregation by composite cement could assist bone healing.The controlled degradation with simultaneous entrapment of composite cement within the osteoid tissues and complete repair of infected cortical defects(holes)in rabbit tibia at 6 weeks indicated the excellent anti-infective and osteoconductive properties of composite cement.Thus,the animal study demonstrated the superiority of composite over injectable antibiotic therapy based on infection reso-lution and bone regeneration.We thereby conclude that the composite cement can be effectively applied in the treatment of resistant cases of chronic osteomyelitis.