Controlled Release of BMP-2 from Alginate Nanohydrogels Enhanced Osteogenic Differentiation of Human Bone Marrow Stromal Cells

Hyun Ju Lim; Han Do Ghim; Jin Hyun Choi; Ho Yun Chung; Jeong Ok Lim

Macromolecular Research, Vol.18, No.8, 787-792, August, 2010

DOI10.1007/s13233-010-0804-6 Export Citation

Controlled Release of BMP-2 from Alginate Nanohydrogels Enhanced Osteogenic Differentiation of Human Bone Marrow Stromal Cells

Hyun Ju Lim^{1, 2}, Han Do Ghim^{1, 3}, Jin Hyun Choi^{1, 2}, Ho Yun Chung^{4, 2}, and Jeong Ok Lim^{2, 5, †}

¹Department of Advanced Organic Materials Science and Engineering, Kyungpook National University, Daegu, 702-701, Korea
²Joint Institute for Regenerative Medicine, Kyungpook National University, Daegu, 700-721, Korea
³, Korea
⁴Department of Plastic & Reconstructive Surgery, School of Medicine, Kyungpook National University, Daegu, 700-721, Korea
⁵Biomedical Research Institute, School of Medicine, Kyungpook National University Hospital, Daegu, 700-721, Korea

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A new controlled release system is proposed for bone morphogenetic proteins (BMP)-induced osteoblastic growth and differentiation of the human bone marrow stromal cells (hBMSCs) using injectable nanohydrogels. Alginate nanohydrogels (ANH) containing BMP-2 (BMP-2@ANH) were prepared using a reverse emulsificationdiffusion technique. The mean particle diameter of the BMP-2@ANH measured by dynamic light scattering was 520 nm. The proliferation of hBMSCs was promoted with the BMP-2@ANH. The controlled release of BMP-2 from the BMP-2@ANH enhanced the differentiation of hBMSCs into osteoblasts, which was confirmed by RT-PCR and alkaline phosphate activity. With the BMP-2@ANH, calcification and phosphate deposits on the cells were confirmed by alizarin red-S staining and von-kossa staining, respectively, showing that the differentiation of hBMSCs into osteoblasts was activated by the BMP-2 released from the BMP-2@ANH. Growth factor delivery using a nanohydrogel is a potential method for facilitating the differentiation of stem cells in vivo.

Keywords:human bone marrow stromal cells;alginate nanohydrogel;BMP-2;controlled release;osteogenic differentiation

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[Referenced By]

[1] Biondi M, Ungarom F, Quaglia F, Netti PA, Adv. Drug Deliv. Rev., 60, 229 (2008)

[2] Barvosa MA, Granja PL, Narrias CC, Amaral IF, ITBM-RBM, 26, 212 (2005)

[3] Malafaya PB, Silva GA, Reis RL, Adv. Drug Deliv. Rev., 59, 207 (2007)

[4] Riedel GE, Valenin OA, Orthopedics, 22, 669 (1999)

[5] Smidsrod O, Draget KI, Carbohyd. Eur., 14, 6 (1996)

[6] Ashton RS, Banerjee A, Punyani S, Schaffer DV, Kane RS, Biomaterials, 28, 5518 (2007)

[7] Liu HW, Chen CH, Tsai CL, Hsiue GH, Bone, 39, 825 (2006)

[8] Chen PB, Mooney DJ, Pham. Res., 20, 1103 (2003)

[9] Saltzman WM, Olbricht WL, Nat. Rev. Drug Discov., 1, 177 (2002)

[10] Langer R, Mol. Ther., 1, 12 (2000)

[11] Edelman ER, Mathiowitz E, Langer R, Klagsbrun M, Biomaterials, 12, 619 (1991)

[12] Tabata Y, Hijikata S, Ikada Y, J. Control. Release, 31, 189 (1994)

[13] Munirzzaman M, Tabata Y, Ikada Y, J. Biomater. Sci.-Polym. Ed., 9, 459 (1998)

[14] Tabata Y, Ikada Y, Adv. Drug Deliv. Rev., 31, 287 (1998)

[15] Tabata Y, Ikada Y, Biomaterials, 20, 2169 (1999)

[16] Mizuno K, Yamamura K, Yano K, Osada T, Saeki S, Takimoto N, Sakurai T, Nimura Y, J. Biomed. Mater. Res., 64A, 177 (2003)

[17] Kaps C, Bramlage C, Smolian H, Haisch A, Ungethum U, Burmester GR, Gross C, Haupl T, Arthritis Rheum, 46, 1499 (2002)

[18] Pound JC, Green DW, Chaudhuri JB, Mann S, Roach HI, Oreffo ROC, Tissue Eng., 12, 2789 (2006)

[19] Stevens MM, Qunadilo HF, Langer R, Shastri VP, Biomaterials, 25, 887 (2004)

[20] Stevens MM, Marini RP, Martin I, Langer R, Shastri VP, J. Orthop., 22, 1114 (2004)

[21] Erickson GR, Gimble JM, Franklin DM, Rice HE, Awad H, Guilak F, Biochem. Biophys. Res. Commun., 290(2), 763 (2002)

[22] Awad HA, Wkckham MQ, Leddy HA, Ginble JM, Guilak F, Biomaterials, 25, 3211 (2004)

[23] Dausse Y, Grossin L, Miralles G, Pelletier S, Mainard D, Hubert P, Baptiste D, Gillet P, Dellacherie E, Netter P, Payan E, Osteoarthr. Cartil., 11, 16 (2003)

[24] Xu XL, Lou J, Tang TT, Ng KW, Zhang JH, Yu CF, Dai KR, J. Biomed. Mater. Res., B Appl. Biomater., 75B, 289 (2005)

[25] Lee SH, Shin HS, Adv. Drug Deliv. Rev., 59, 339 (2007)

[26] Oldham JB, Lu L, Zhu X, Porter BD, Hefferan TE, Larson DR, Currier BL, Mikos AG, Yaszemski MJ, J. Biomech. Eng. -Trans. ASME, 122, 289 (2000)

[27] Zhu G, Mallery SR, Schwendeman SP, Nat. Biotechnol., 18, 52 (2000)

[28] Lee SM, Yoo ES, Ghim HD, Lee SJ, Macromol. Res., 17(3), 168 (2009)

[29] Xu HH, Weir MD, Simon CG, Dent. Mater., 24, 1212 (2008)

[30] Dechaseaux F, Sensebe L, Heymann D, Trends Mol. Med, 15, 417 (2009)