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

作者:Subbiah Ramesh; Du Ping; Hwang Mintai Peter; Kim In Gul; Van Se Young; Noh Yong Kwan; Park Hansoo; Park Kwideok*
来源:Macromolecular Research, 2014, 22(12): 1320-1329.
DOI:10.1007/s13233-014-2183-x

摘要

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 A mu m in diameter with an average core size of 90 +/- 13 A mu m, 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 A mu L/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.

  • 出版日期2014-12