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Dual growth factor-loaded core-shell polymer microcapsules can promote osteogenesis and angiogenesis

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Abstract

Growth factors (GFs) are very critical in stem cell differentiation and tissue regeneration. Therefore GF delivery carriers have been a major subject in tissue engineering research. In this study, we prepare and optimize core-shell microcapsules (C-S MCs) for dual GF delivery. The C-S MCs, composed of an alginate shell and poly(lactic-co-glycolic) acid (PLGA) core, are fabricated using an electrodropping method via custom-made coaxial needles. They are 198±38 µm in diameter with an average core size of 90±13 µm, and they are fabricated using an alginate concentration of 1% (w/v), an electrical voltage of 11 kV, and an inner syringe flow rate of 50 µL/min. Using this platform, dual GFs, bone morphogenetic protein (BMP-2) and vascular endothelial growth factor (VEGF) are encapsulated in the alginate shell and PLGA core, respectively. In vitro release tests of dual GF-loaded C-S MCs reveal early release of BMP-2, followed by VEGF on a temporal release profile of 28 days. In vitro study of the dual GF-loaded MCs demonstrates their osteogenic activity with preosteoblasts; osteogenic markers (osteocalcin and type I collagen) are upregulated and both calcium content and alkaline phosphatase (ALP) activity also increased. In addition, C-S MCs combined with collagen and preosteoblasts were subcutaneously transplanted to the dorsal region of nude mice for 3 weeks. Analysis of the retrieved constructs exhibits that both osteogenesis and angiogenesis were more active in the group containing dual GF-loaded MCs, along with deep penetration of blood vessels inside the construct, compared to blank MCs or single GF (BMP-2)-loaded MCs. This study proposes a dual GF delivery carrier using C-S MCs and demonstrates the feasibility of C-S MCs in the induction of osteogenesis and angiogenesis.

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Authors and Affiliations

  1. Department of Biomedical Engineering, Korea University of Science and Technology (UST), Daejon, 305-350, Korea

    Ramesh Subbiah, Ping Du, Se Young Van & Kwideok Park

  2. Center for Biomaterials, Korea Institute of Science and Technology (KIST), Seoul, 136-130, Korea

    Ramesh Subbiah, Ping Du, Mintai Peter Hwang, In Gul Kim, Se Young Van, Yong Kwan Noh & Kwideok Park

  3. Department of Biomedical Engineering, School of Medicine, Kyunghee University, Seoul, 130-701, Korea

    Yong Kwan Noh

  4. School of Integrative Engineering, Chung-Ang University, Seoul, 156-071, Korea

    Hansoo Park

Authors
  1. Ramesh Subbiah
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  2. Ping Du
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  3. Mintai Peter Hwang
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  4. In Gul Kim
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  5. Se Young Van
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  6. Yong Kwan Noh
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  7. Hansoo Park
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  8. Kwideok Park
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Correspondence to Kwideok Park.

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The image from this article is used as the cover image of the Volume 22, Issue 12

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Subbiah, R., Du, P., Hwang, M.P. et al. Dual growth factor-loaded core-shell polymer microcapsules can promote osteogenesis and angiogenesis. Macromol. Res. 22, 1320–1329 (2014). https://doi.org/10.1007/s13233-014-2183-x

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  • DOI: https://doi.org/10.1007/s13233-014-2183-x

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