A polyethylene glycol-based hydrogel as macroporous scaffold for tumorsphere formation of glioblastoma multiforme

Yoonjee Oh; Junghwa Cha; Seok-Gu Kang; Pilnam Kim

Journal of Industrial and Engineering Chemistry, Vol.39, 10-15, July, 2016

DOI10.1016/j.jiec.2016.05.012 Export Citation

A polyethylene glycol-based hydrogel as macroporous scaffold for tumorsphere formation of glioblastoma multiforme

Yoonjee Oh, Junghwa Cha, Seok-Gu Kang¹, and Pilnam Kim^†

Department of Bio and Brain Engineering, KAIST, Daejeon, 305-701, Republic of Korea
¹Department of Neurosurgery, Severance Hospital, Yonsei University College of Medicine, Seoul, 120-752, Republic of Korea

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We report a formation of macroporous scaffold which is based on polyethylene glycol (PEG)-based alginate (ALG) interpenetrating polymer network (IPN) hydrogel. Using this scaffold, we assess the tumorsphere (TS)-forming ability of glioma cancer stem cells (gCSCs), which subpopulation has been highlighted as a main cause of therapeutic resistance due to self-renewal and potential of differentiation properties. Although there have been numerous methods to study the TSs, however, there is no plausible method to evaluate the formation of single gCSC cell-derived TSs, due to fusion-induced cell aggregation. To provide reliable assessment, the PEGDA hydrogel interpenetrated with ALG was fabricated as macroporous scaffold for TS formation of patient-derived gCSCs. With UV-ionic dual crosslinking process, the pore size of PEGDA-ALG hydrogel is magnified enough to be applied as a macroporous scaffold, providing increased internal voids for TS growth and expansion. As a result, within macroporous scaffold, the multiple number of single gCSC-derived TSs was successfully formed inside the structural voids.

Keywords:Polyethylene glycol;Macroporous hydrogel;Tumorsphere;Glioblastoma multiform

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[3] Eramo A, Ricci-Vitiani L, Zeuner A, Pallini R, Lotti F, Sette G, Pilozzi E, Larocca LM, Peschle C, De Maria R, Cell Death Differ., 13, 1238 (2006)

[4] Weiswald LB, Bellet D, Dangles-Marie V, Neoplasia, 17, 1 (2015)

[5] Lee CH, Yu CC, Wang BY, Chang WW, Oncotarget, 7, 1215 (2015)

[6] Lee M, Yang K, Hwang YH, Byun Y, Lee DY, Cho SW, Lee H, Adv. Healthc. Mater., 4, 511 (2015)

[7] Yang X, Sarvestani SK, Moeinzadeh S, He X, Jabbari E, Tissue Eng. Part A, 19, 669 (2013)

[8] Wong SY, Ulrich TA, Deleyrolle LP, MacKay JL, Lin JM, Martuscello RT, Jundi MA, Reynolds BA, Kumar S, Cancer Res., 75, 1113 (2015)

[9] Fennema E, Rivron N, Rouwkema J, van Blitterswijk C, de Boer J, Trends Biotechnol., 31, 108 (2013)

[10] Pastrana E, Silva-Vargas V, Doetsch F, Cell Stem Cell, 8, 486 (2011)

[11] Giobbe GG, Zagallo M, Riello M, Serena E, Masi G, Barzon L, Di Camillo B, Elvassore N, Biotechnol. Bioeng., 109(12), 3119 (2012)

[12] Yu H, Meyvantsson I, Shkel IA, Beebe DJ, Lab Chip, 5, 1089 (2005)

[13] Raic A, Rodling L, Kalbacher H, Lee-Thedieck C, Biomaterials, 35, 929 (2014)

[14] Raeber GP, Lutolf MP, Hubbell JA, Biophys. J., 89, 1374 (2005)

[15] Russell RJ, Axel AC, Shields KL, Pishko MV, Polymer, 42(11), 4893 (2001)

[16] Nguyen QT, Hwang Y, Chen AC, Varghese S, Sah RL, Biomaterials, 33, 6682 (2012)

[17] Kutty JK, Cho E, Lee JS, Vyavahare NR, Webb K, Biomaterials, 28, 4928 (2007)

[18] Zhang HB, Wang L, Song L, Niu GG, Cao H, Wang GJ, Yang HA, Zhu SQ, J. Appl. Polym. Sci., 121(1), 531 (2011)

[19] Ford MC, Bertram JP, Hynes SR, Michaud M, Li Q, Young M, Segal SS, Madri JA, Lavik EB, Proc. Natl. Acad. Sci. U.S.A., 103, 2512 (2006)

[20] Keskar V, Marion NW, Mao JJ, Gemeinhart RA, Tissue Eng. Part A, 15, 1695 (2009)

[21] Gunbas ID, Sezer UA, Iz SG, Gurhan ID, Hasirci N, Ind. Eng. Chem. Res., 51(37), 11946 (2012)

[22] Yim ES, Zhao B, Myung D, Kourtis LC, Frank CW, Carter D, Smith RL, Goodman SB, J. Biomed. Mater. Res. A, 91a, 894 (2009)

[23] Mahou R, Meier RPH, Buhler LH, Wandrey C, Materials, 7, 275 (2014)

[24] Desai NP, Sojomihardjo A, Yao Z, Ron N, Soon-Shiong P, J. Microencapsul., 17, 677 (2000)

[25] Sun JC, Tan HP, Materials, 6, 1285 (2013)

[26] Utech S, Prodanovic R, Mao AS, Ostafe R, Mooney DJ, Weitz DA, Adv. Healthcare Mater., 4, 1628 (2015)

[27] Annabi N, Nichol JW, Zhong X, Ji C, Koshy S, Khademhosseini A, Dehghani F, Tissue Eng. Part B: Rev., 16, 371 (2010)

[28] Zhu JH, Wang XW, Ng S, Quek CH, Ho HT, Lao XJ, Yu H, J. Biotechnol., 117, 355 (2005)

[29] Kong BH, Park NR, Shim JK, Kim BK, Shin HJ, Lee JH, Huh YM, Lee SJ, Kim SH, Kim EH, Park EK, Chang JH, Kim DS, Kim SH, Hong YK, Kang SG, Lang FF, Childs Nerv. Syst., 29, 217 (2013)

[30] Curcio E, Salerno S, Barbieri G, De Bartolo L, Drioli E, Bader A, Biomaterials, 28, 5487 (2007)