title: Enhancement of bone formation with a synthetic matrix containing bone morphogenetic protein-2 by the addition of calcium citrate.
abstract: OBJECTIVE
  The aim of the study was to test whether calcium citrate combined with rhBMP-2 was able to enhance bone regeneration compared with a matrix containing only rhBMP-2.
  
  
  METHODS
  In each of experimental mice, one cylinder of calcium citrate-rhBMP-2 or rhBMP-2 alone was implanted into the thigh muscle pouches of the mouse. The following two treatment modalities were randomly allocated: (1) empty control with rhBMP-2 alone in a gelatin matrix and (2) a gelatin matrix including both calcium citrate and BMP-2. After several weeks, bone granules were obtained by histological analysis.
  
  
  RESULTS
  Histomorphometric analysis showed the greatest amount of newly formed bone was observed in the group that contained 10.0 mg calcium citrate with 2.0 mg rhBMP-2 (p < 0.05). Quantitative histomorphometry revealed in the calcium citrate-rhBMP-2 group an obvious increase in the fractional area and the average new bone mineral density of newly formed bone at 2, 4 and 6 weeks than in the rhBMP-2 group (p < 0.05). At 2 weeks time-point, the mature cancellous bone had formed in the calcium citrate-rhBMP-2 group.
  
  
  CONCLUSIONS
  From this study, it can be concluded that calcium citrate combined with rhBMP-2 significantly enhances bone regeneration in muscle. This synthetic gelatin matrix containing calcium citrate/gelatin granules fulfils a number of criteria required for an ideal carrier system for rhBMP-2. The calcium ions that calcium citrate releases into the surrounding environment can activate bone formation when used as part of a combination of calcium citrate and BMP-2.
authors.affiliation: Department of Orthopaedic Surgery, Second Affiliated Hospital of Wenzhou Medical College, Wenzhou, Zhejiang, China.
authors.forename: Wei
authors.initials: W
authors.lastname: Wang
authors.forename: Qingyu
authors.initials: Q
authors.lastname: Chen
authors.forename: Xiucui
authors.initials: X
authors.lastname: Li
authors.forename: Wei
authors.initials: W
authors.lastname: Zhang
authors.forename: Lei
authors.initials: L
authors.lastname: Peng
authors.forename: Liming
authors.initials: L
authors.lastname: Wang
authors.forename: Zhongqin
authors.initials: Z
authors.lastname: Lin
authors.forename: Huazi
authors.initials: H
authors.lastname: Xu
authors.forename: Shifeng
authors.initials: S
authors.lastname: Song
authors.forename: Xiaolei
authors.initials: X
authors.lastname: Zhang
authors.forename: Shaowen
authors.initials: S
authors.lastname: Cheng
authors.forename: Dongquan
authors.initials: D
authors.lastname: Kou
authors.forename: Chuanzhu
authors.initials: C
authors.lastname: Lv
authors.forename: Ziming
authors.initials: Z
authors.lastname: Yu
mesh_terms: D000818:Animals; D055396:Bone Morphogenetic Protein 2 / Q000494:pharmacology*; D001861:Bone Regeneration / Q000187:drug effects*; D019355:Calcium Citrate / Q000494:pharmacology*; D005782:Gels; D008297:Male; D051379:Mice; D010012:Osteogenesis / Q000187:drug effects*; D011994:Recombinant Proteins / Q000494:pharmacology; D016212:Transforming Growth Factor beta / Q000494:pharmacology*
chemical_list: D055396:Bone Morphogenetic Protein 2; D005782:Gels; D011994:Recombinant Proteins; D016212:Transforming Growth Factor beta; C499469:recombinant human bone morphogenetic protein-2; D019355:Calcium Citrate