title: Assessing the character of the rhBMP-2- and vancomycin-loaded calcium sulphate composites in vitro and in vivo.
abstract: 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.
authors.affiliation: Department of Orthopaedics, 2nd Affiliated Hospital, School of Medicine, Zhejiang University, Hangzhou 310009, China.
authors.forename: Yulu
authors.initials: Y
authors.lastname: Wang
authors.forename: Xinqiang
authors.initials: X
authors.lastname: Wang
authors.forename: Hang
authors.initials: H
authors.lastname: Li
authors.forename: Deting
authors.initials: D
authors.lastname: Xue
authors.forename: Zhongli
authors.initials: Z
authors.lastname: Shi
authors.forename: Yiying
authors.initials: Y
authors.lastname: Qi
authors.forename: Qiang
authors.initials: Q
authors.lastname: Ma
authors.forename: Zhijun
authors.initials: Z
authors.lastname: Pan
mesh_terms: D000704:Analysis of Variance; D000818:Animals; D055396:Bone Morphogenetic Protein 2 / Q000008:administration & dosage / Q000493:pharmacokinetics*; D002133:Calcium Sulfate / Q000494:pharmacology*; D002478:Cells, Cultured / Q000187:drug effects; D004195:Disease Models, Animal; D004337:Drug Carriers / Q000008:administration & dosage / Q000493:pharmacokinetics; D016503:Drug Delivery Systems / Q000379:methods*; D004797:Enzyme-Linked Immunosorbent Assay; D005434:Flow Cytometry; D007150:Immunohistochemistry; D066298:In Vitro Techniques; D008297:Male; D010019:Osteomyelitis / Q000188:drug therapy*; D011817:Rabbits; D011897:Random Allocation; D051381:Rats; D017207:Rats, Sprague-Dawley; D013977:Tibia / Q000187:drug effects* / Q000473:pathology; D020858:Tissue and Organ Harvesting; D014640:Vancomycin / Q000008:administration & dosage / Q000493:pharmacokinetics*
chemical_list: D055396:Bone Morphogenetic Protein 2; D004337:Drug Carriers; D014640:Vancomycin; D002133:Calcium Sulfate