Assessing the character of the rhBMP-2- and vancomycin-loaded calcium sulphate composites in vitro and in vivo

• Published in: Archives of orthopaedic and trauma surgery 2011-07, Vol.131 (7), p.991-1001
• Main Authors: Wang, Yulu, Wang, Xinqiang, Li, Hang, Xue, Deting, Shi, Zhongli, Qi, Yiying, Ma, Qiang, Pan, Zhijun
• Format: Article
• Language: English
• Subjects: Analysis of Variance; Animals; Antibiotics; Basic Science; Bone Morphogenetic Protein 2 - administration & dosage; Bone Morphogenetic Protein 2 - pharmacokinetics; Calcium Sulfate - pharmacology; Cells, Cultured - drug effects; Defects; Disease Models, Animal; Drug Carriers - administration & dosage; Drug Carriers - pharmacokinetics; Drug Delivery Systems - methods; Enzyme-Linked Immunosorbent Assay; Flow Cytometry; Immunohistochemistry; In Vitro Techniques; Male; Medicine; Medicine & Public Health; Orthopedics; Osteomyelitis - drug therapy; Rabbits; Random Allocation; Rats; Rats, Sprague-Dawley; Tibia - drug effects; Tibia - pathology; Tissue and Organ Harvesting; Vancomycin - administration & dosage; Vancomycin - pharmacokinetics
• ISSN: 0936-8051; 1434-3916
• DOI: 10.1007/s00402-011-1269-6

Background The treatment of contaminated and infected bone defects remains an intractable problem and the ideal approach is to control infection and repair the bone defect at the same time. Thus, developing an osteoconductive bone graft composite with antibiotic and growth factor release capabilities as well as osteogenesis-matched degradation properties is necessary. A new calcium sulphate composite consisting of vancomycin and rhBMP-2 was developed, and the present study assessed its efficiency in vitro and in a rabbit tibial defect model. Methods Firstly, we detected the bioactivity of rhBMP-2 released from the composites by ALP assay in vitro. Then, the released vancomycin in bone tissue within 1 cm from implanted site was detected by HLPC at 1, 3, 5, 7, 14, 21 and 28 days after implantation. The rhBMP-2 concentration of tissues around the defects was also detected by ELISA. Histomorphometry and histomorphometrical analysis at 5, 14 and 28 days post-implantation was done for assessing its osteoinductivity for bone defects. Results The results showed rhBMP-2 was still active in vitro at 29 days. In vivo, the composite released an initial bolus of vancomycin and rhBMP-2 to the bone followed by gradual release for more than 14 and 21 days, respectively. The histomorphometry indicated that the composite significantly augmented new bone formation in the defect compared to the control. Conclusions This composite may be a potential therapeutic agent for contaminated or infected bone defects due to its concomitant osteoinductive and antibiotic properties.