Chinese Journal of Tissue Engineering Research ›› 2014, Vol. 18 ›› Issue (52): 8405-8408.doi: 10.3969/j.issn.2095-4344.2014.52.008

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Preparation and performance of recombinant human bone morphogenetic protein-2-poly(hydroxybutyrate-co-hydroxyoctanoate) nanospheres

Wang Xiao-dong1, Zhang Yong-hong2   

  1. 1Department of Orthopedics, Shanxi Medical University, Taiyuan 030001, Shanxi Province, China; 2Second Hospital of Shanxi Medical University, Taiyuan 030001, Shanxi Province, China
  • Revised:2014-09-29 Online:2014-12-17 Published:2014-12-17
  • Contact: Zhang Yong-hong, M.D., Chief physician, Second Hospital of Shanxi Medical University, Taiyuan 030001, Shanxi Province, China
  • About author:Wang Xiao-dong, Master, Physician, Department of Orthopedics, Shanxi Medical University, Taiyuan 030001, Shanxi Province, China

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Abstract:

BACKGROUND:Bone morphogenetic protein-2 can increase the production of chondrocytes and progenitor cell matrix, enhance tissue inhibitor of metalloproteinase-1, sox9, type II collagen and aggrecan expressions, with the induction of mesenchymal cell migration, proliferation, and differentiation, leading to cartilage and bone formation.

OBJECTIVE: Using the biodegradable copolymer of poly(hydroxybutyrate-co-hydroxyoctanoate)-based materials to fabricate recombinant human bone morphogenetic-2-poly(hydroxybutyrate-co-hydroxyoctanoate) sustained release nanospheres and to investigate its morphology, particle distribution, drug loading, encapsulation efficiency, in vitro release time, and bioactivity.
METHODS: The recombinant human bone morphogenetic-2-poly(hydroxybutyrate-co-hydroxyoctanoate) sustained release nanospheres were prepared by multiple emulsion volatilizing method. Porcine chondrocytes were isolated and cultured in vitro. There were three groups: group 1, no drugs were added into the medium serving as control group; group 2, 20 μg/L recombinant human bone morphogenetic-2 was added; group 3, 20 μg/L recombinant human bone morphogenetic-2-poly(hydroxybutyrate-co-hydroxyoctanoate) sustained release nanospheres were added. The effective concentration was 55 μg/L for recombinant human bone morphogenetic-2 in group 2, and 100 μg/L for recombinant human bone morphogenetic-2-poly(hydroxybutyrate-co-hydroxyoctanoate) sustained release nanospheres in group 3. Proliferative capacity of chondrocytes was detected using 3-(4,5-dimethylthiazol-2-yl)-2,5- diphenyltetrazolium bromide assay. In vitro release profile and biological activity were observed under simulated in vivo conditions.
RESULTS AND CONCLUSION: The surface of nanospheres was smooth and rounded, and the nanosheres had uniform size and particle size of 231-415 nm. Under scanning electron microscope, the average particle size was

323 nm. Microsphere encapsulation efficiency and drug loading were (79.63±0.16)% and (1.92±0.16)%, respectively. Within 15 days, in vitro release of recombinant human bone morphogenetic protein-2 from recombinant human bone morphogenetic-2-poly(hydroxybutyrate-co-hydroxyoctanoate) sustained release nanospheres lasted and increased. The nanospheres had biological activity and could promote chondrocyte proliferation. Biological activity of recombinant human bone morphogenetic-2 was lower than that of the recombinant human bone morphogenetic-2-poly (hydroxybutyrate-co-hydroxyoctanoate) sustained release nanospheres. It prompts that the encapsulation efficiency, drug loading, in vitro release and biological activity of the recombinant human bone morphogenetic-2- poly(hydroxybutyrate-co-hydroxyoctanoate) sustained release nanospheres are basically consistent with the general requirements of cartilage tissue engineering.


中国组织工程研究杂志出版内容重点：生物材料；骨生物材料; 口腔生物材料; 纳米材料; 缓释材料; 材料相容性；组织工程


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Key words: biocompatible materials, bone morphogenetic proteins, nanotechnology, nanospheres

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