Dual-delivery of vancomycin and icariin from an injectable calcium phosphate cement-release system for controlling infection and improving bone healing

Abstract

Infectious bone diseases following severely contaminated open fractures are frequently encountered in clinical practice. It is difficult to successfully repair bone and control infection at the same time. To identify a better treatment method, we prepared a dual-drug release system that was comprised of icariin (IC, a natural osteoinductive molecule), vancomycin (VA) and injectable calcium phosphate cement (CPC). The ultrastructure of the dual-drug release system was evaluated by scanning electron microscopy and the biocompatibility was assessed by cell culture. In addition, the release kinetics of IC and VA were respectively investigated by using high‑performance liquid chromatography. Finally, this system was used to repair Staphylococcus aureus-contaminated bone defects in a rabbit model. Twelve weeks after the implantation of IC-VA/CPC, the contaminated bone defects were completely repaired, with significantly improved formation of lamellar bone and recanalization of the marrow cavity compared with the controls (CPC without antibiotics or osteoinductive agent). These results demonstrate that this dual-drug release system, with its concomitant antibiotic and osteoinductive properties, has significant potential for the treatment of contaminated bone injury or infectious bone disease.