Chinese Journal of Tissue Engineering Research ›› 2011, Vol. 15 ›› Issue (25): 4583-4586.doi: 10.3969/j.issn.1673-8225.2011.25.007

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Enhancement of bone formation by recombinant human bone morphogenetic protein-2/chitosan bone biomaterials

Wang Ding-ding1, Zeng Rong2, Yang Min-er1, He Jian-xian1, Chen Yang3, He Shui-lian3, Chen An-an3, Zhou Zhi-you3, Yuan Li-ying4, Wang Ju3   

  1. 1Institute of Life Science and Biological Pharmacy, Guangdong Pharmaceutical University, Guangzhou  510006, Guangdong Province, China
    2Department of Materials Science and Engineering, Jinan University, Guangzhou  510632, Guangdong Province, China
    3College of Life Science and Technology, Jinan University, Guangzhou  510632, Guangdong Province, China
    4The Third Kindergarten Affiliated to Jilin University, Changchun  130021, Jilin Province, China
  • Received:2011-03-04 Revised:2011-03-29 Online:2011-06-18 Published:2014-01-10
  • Contact: Wang Ju, Doctor, Associate investigator, College of Life Science and Technology, Jinan University, Guangzhou 510632, Guangdong Province, China wang_ju1688@yahoo.cn
  • About author:Wang Ding-ding☆, Doctor, Lecturer, Institute of Life Science and Biological Pharmacy, Guangdong Pharmaceutical University, Guangzhou 510006, Guangdong Province, China wangdingding305@163.com
  • Supported by:

    Tackle Key Program of Guangdong Province, No. 2009B030801237*; Action Plan of Enterprise Technology Correspondent, Guangdong Educational Bureau & Guangdong Science and Technology Bureau, No. 2009B090600134*; the National Natural Science Foundation of China, No. 81000923*

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Abstract:

BACKGROUND: The recombinant human bone morphogenetic protein-2 (rhBMP-2) administered in solution often loses its bioactivity in a short time and does not always exhibit efficacy required in bone regeneration in vivo. It would be ideal to develop a system for the sustained delivery of biologically active rhBMP-2 over an extended period of time.
OBJECTIVE: To evaluate rhBMP-2 sustained delivery and osteoinductive effects of bone biomaterials which were combined with chitosan films containing rhBMP-2.
METHODS: ①The rhBMP-2 was added into a chitosan solution to prepare chitosan films which were spread on the bone materials. The effect of slow release was analyzed by ELISA assays. ②In vitro, the osteoinductive to differentiation marker (osteocalcin) of C2C12 cells after induction of rhBMP-2/chitosan (CS) bone biomaterials was assayed by Alizarin red staining.  ③Intramuscular implantation test was made in vivo, rhBMP-2/CS carriers were implanted in muscles of the hind leg of rat for two weeks. The amount of calcium deposited in the implants was measured to assay bioactivity.
RESULTS AND CONCLUSION: ①A scanning electron micrograph of the rhBMP-2/CS bone biomaterials showed uniform distribution of chitosan films on the material surface with rhBMP-2 scattering like cluster. ②An abrupt rhBMP-2 release from rhBMP-2/CS carriers was observed. 50% of the loaded rhBMP-2 was released in 4 days. Thereafter, the release rate was nearly constant until day 12 when 90% of rhBMP-2 was released. All of it was released by day 18 at last. ③In vitro rhBMP-2 released from the rhBMP-2/CS carriers stimulated an increase in osteocalcin of C2C12 cells after 4 weeks. ④In vivo bone formation studies showed the rhBMP-2/CS biomaterials induced bone formation to a much greater extent than control groups by Ca2+ test assay. These results demonstrate that the rhBMP-2/CS bone biomaterials delivery system is capable of potentiating the osteogenic efficacy of rhBMP-2 and underscore its importance as a possible bone regeneration strategy.

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