Preparation Of An Injectable Chitosan/hydroxyapatite Bone Cement And Its Application As Drug Sustainedrelease Carrier

Background: Clinically,bone defects caused by tumors or tuberculosis are very common,and the repair of bone defects is a difficult problem for clinicians and researchers.Due to its good biocompatibility,osteoconductivity and biodegradability,calcium phosphate cement（CPC）has attracted the attention of many researchers.In addition,CPC not only can be used as a bone grafting material to repair bone defects,but also can be used as a drug release carrier.Therefore,it is of great significance to prepare drug-loaded CPC for the treatment of bone tuberculosis or bone tumor.Objective: The main goal of this work was to prepare an injectable chitosan/hydroxyapatite（CS/HA）bone cement as a drug release carrier.Rifampicin（RFP）and methotrexate（MTX）were used as model drugs.The physicochemical properties,biological properties and biosafety of CS/HA（or drug-loaded CS/HA）bone cement were evaluated.The drug release behavior of drug-loaded CS/HA bone cement was assessed in vitro as well.It was expected to provide experimental data for CS/HA bone cement as a drug sustained-release carrier.It was anticipated that CS/HA bone cement was a novel bone grafting material for postoperative bone defect repairing.Methods: CS/HA composite was prepared by co-precipitation method.An injectable CS/HA bone cement was prepared by using CS/HA composite powder as solid phase and citric acid as liquid phase.The physicochemical properties,such as injectability,setting time,anti-washout ability,water absorption,and mechanical properties were evaluated.The biocompatibility and biodegradability of the cements were assessed as well.The sustained drug release effect of the CS/HA cement was studied in vitro via using RFP and MTX as drug models.Results: CS/HA bone cement has suitable setting time,good injectability anti-washout ability,mechanical strength,degradability and biocompatibility.CS/HA bone cement has a significant in vitro sustained-release effect on RFP and MTX.RFP did not significantly affect the injectability,anti-washout ability and setting time of bone cement,but RFP increased the porosity and decreased the compressive strength of bone cement.MTX also had no significant effect on the injectability,anti-washout ability and setting time of bone cement,but MTX increased the porosity and decreased the compressive strength of bone cement.MTX-CS/HA bone cement has obvious inhibitory effect on MG-63 osteosarcoma cells.Conclusion: The injectable CS/HA bone cement has good physicochemical and biological properties.CS/HA bone cement has a good sustained-release effect on RFP and MTX.It has a good application prospect as a drug sustained-release carrier.Drug-loaded CS/HA bone cement is an excellent artificial bone material,which has dual functions of repairing bone defect as well as drug treatment.