Efficient delivery of recombinant human bone morphogenetic protein (rhBMP‑2) with dextran sulfate‑chitosan microspheres

Xia,Yuan‑Jun; Xia,Hong; Chen,Ling; Ying,Qing‑Shui; Yu,Xiang; Li,Li‑Hua; Wang,Jian‑Hua; Zhang,Ying

doi:10.3892/etm.2018.5849

Efficient delivery of recombinant human bone morphogenetic protein (rhBMP‑2) with dextran sulfate‑chitosan microspheres

Authors:
- Yuan‑Jun Xia
- Hong Xia
- Ling Chen
- Qing‑Shui Ying
- Xiang Yu
- Li‑Hua Li
- Jian‑Hua Wang
- Ying Zhang
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Affiliations: Department of Trauma Orthopedics, Hospital of Orthopaedics, Guangzhou General Hospital of Guangzhou Military Command, Guangzhou, Guangdong 510010, P.R. China, Department of Traditional Chinese Medicine, Southern Medical University, Guangzhou, Guangdong 510515, P.R. China
Published online on: February 7, 2018 https://doi.org/10.3892/etm.2018.5849
Pages: 3265-3272
Copyright: © Xia et al. This is an open access article distributed under the terms of Creative Commons Attribution License.

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Abstract

Bone morphogenetic protein‑2 (BMP‑2) serves an important role in the development of bone and cartilage. However, administration of BMP‑2 protein alone by intravenous delivery is not very effective. Sustained delivery of stabilized BMP‑2 by carriers has been proven necessary to improve the osteogenesis effect of BMP‑2. The present study constructed a novel drug delivery system using dextran sulfate (DS)‑chitosan (CS) microspheres and investigated the efficiency of the delivery system on recombinant human bone morphogenetic protein (rhBMP‑2). The microsphere morphology, optimal ratio of DS/CS/rhBMP‑2, and drug loading rate and entrapment efficiency of rhBMP‑2 CS nanoparticles were determined. L929 cells were used to evaluate the cytotoxicity and effect of DS/CS/rhBMP‑2 microspheres on cell proliferation. Differentiation study was conducted using bone marrow mesenchymal stem cells (BMSCs‑C57) cells treated with DS/CS/rhBMP‑2 microspheres or the control microspheres. The DS/CS/rhBMP‑2 microspheres delivery system was successfully established. Subsequent complexation of rhBMP‑2‑bound DS with polycations afforded well defined microspheres with a diameter of ~250 nm. High protein entrapment efficiency (85.6%) and loading ratio (47.245) µg/mg were achieved. Release of rhBMP‑2 from resultant microspheres persisted for over 20 days as determined by ELISA assay. The bioactivity of rhBMP‑2 encapsulated in the CS/DS microsphere was observed to be well preserved as evidenced by the alkaline phosphatase activity assay and calcium nodule formation of BMSCs‑C57 incubated with rhBMP‑2‑loaded microspheres. The results demonstrated that microspheres based on CS‑DS polyion complexes were a highly efficient vehicle for delivery of rhBMP‑2 protein. The present study may provide novel orientation for bone tissue engineering for repairing and regenerating bone defects.

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