Synthesis and Characterization of In Situ Gellable Poly(glycerol sebacate)-co-Poly(ethylene glycol) Polymers

So Mi Choi; Yunki Lee; Joo Young Son; Jin Woo Bae; Kyung Min Park; Ki Dong Park

Macromolecular Research, Vol.25, No.1, 85-91, January, 2017

DOI10.1007/s13233-017-5007-y Export Citation

Synthesis and Characterization of In Situ Gellable Poly(glycerol sebacate)-co-Poly(ethylene glycol) Polymers

So Mi Choi^†, Yunki Lee, Joo Young Son, Jin Woo Bae, Kyung Min Park¹, and Ki Dong Park^†

Department of Molecular Science and Technology, Ajou University, Suwon, Gyeonggi 16499, Korea
¹Division of Bioengineering, Incheon National University, Incheon 22012, Korea

E-mail:,

Hydrogels are widely used as implantable scaffolds and drug delivery carriers for biomedical applications. In particular, in situ cross-linkable hydrogels synthesized via enzyme-mediated reaction have received great attention in the field of injectable biomedical research as they have applications in minimally invasive procedures and have easily controllable physicochemical properties (e.g., gelation time, mechanical properties, etc.) under mild conditions. In this study, we synthesized poly(ethylene glycol) (PEG)-co-polymerized poly(glycerol sebacate) (PGS) polymers (PEG-co-PGS) capable of dissolving in aqueous environments and developed injectable hydrogel platforms via a horseradish peroxidase (HRP)-catalyzed cross-linking reaction. To induce in situ gelling, HRP-reactive phenol moieties (tyramine) were covalently conjugated to the PEG-co-PGS polymers, and hydrogel networks were formed in the presence of HRP and hydrogen peroxide (H2O2). The chemical structures of synthesized polymers were confirmed by 1H NMR spectroscopy, and the physicochemical properties of the hydrogels were assessed under varying concentrations of HRP and H2O2 solutions. The gelation time of PEG-co-PGS hydrogels ranged from 12 s to 237 s based on the HRP concentration (0.02-0.25 mg/mL), and the elastic modulus (16-41 Pa) depended on H2O2 concentration. In vitro cytocompatibility studies in human dermal fibroblasts revealed that PEG-co-PGS hydrogels were highly cytocompatible, with no negative effects on cell morphology and viability. In conclusion, our results suggest that PGS-based injectable hydrogels with multi-tunable properties and good cytocompatibility have tremendous potential as injectable scaffolds for tissue engineering applications.

Keywords:in situ forming hydrogel;horseradish peroxidase;hydrogen peroxide;poly(glycerol sebacate);poly(ethylene glycol)

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[Referenced By]

[1] Drury JL, Mooney DJ, Biomaterials, 24, 4337 (2003)

[2] Hoffman AS, Adv. Drug Deliv. Rev., 64, 18 (2012)

[3] Yang JA, Yeom J, Hwang BW, Hoffman AS, Hahn SK, Prog. Polym. Sci, 39, 1973 (2014)

[4] Li Y, Rodrigues J, Tomas H, Chem. Soc. Rev., 41, 2193 (2012)

[5] Sivashanmugam A, Kumar RA, Priya MV, Nair SV, Jayakumar R, Eur. Polym. J., 72, 543 (2015)

[6] Hennink WE, van Nostrum CF, Adv. Drug Deliv. Rev., 64, 223 (2012)

[7] Teixeira LS, Feijen J, van Blitterswijk CA, Dijkstra PJ, Karperien M, Biomaterials, 33, 1281 (2012)

[8] Wennink JWH, Niederer K, Bochynska AI, Teixeira LSM, Karperien M, Feijen J, Dijkstra PJ, Macromol. Symp., 309-310, 213 (2011)

[9] Chen F, Yu S, Liu B, Ni Y, Yu C, Su Y, Zhu X, Yu X, Zhou Y, Yan D, Scientific reports, 6, 20014 (2016)

[10] Moriyama K, Minamihata K, Wakabayashi R, Goto M, Kamiya N, Chem. Commun., 50, 5895 (2014)

[11] Lee Y, Bae JW, Oh DH, Park KM, Chun YW, Sung HJ, Park KD, J. Mater. Chem. B, 1, 2407 (2013)

[12] Lee F, Chung JE, Kurisawa M, Soft Matter, 4, 880 (2008)

[13] Lienemann PS, Lutolf MP, Ehrbar M, Adv. Drug Deliv. Rev., 64, 1078 (2012)

[14] Rai R, Tallawi M, Grigore A, Boccaccini AR, 37, 1051 (2012).

[15] Loh XJ, Karim AA, Owh C, J. Mater. Chem. B, 3, 7641 (2015)

[16] Wang Y, Ameer GA, Sheppard BJ, Langer R, Nat. Biotechnol., 20, 602 (2002)

[17] Kemppainen JM, Hollister SJ, J. Biomed. Mater. Res. A, 94, 9 (2010)

[18] Rai R, Tallawi M, Barbani N, Frati C, Madeddu D, Cavalli S, Graiani G, Quaini F, Roether JA, Schubert DW, Rosellini E, Boccaccini AR, Mater. Sci. Eng. C-Biomimetic Supramol. Syst., 33, 3677 (2013)

[19] Ravichandran R, Venugopal JR, Sundarrajan S, Mukherjee S, Sridhar R, Ramakrishna S, Nanotechnology, 23, 385102 (2012)

[20] Lang N, Pereira MJ, Lee Y, Friehs I, Vasilyev NV, Feins EN, Ablasser K, O'Cearbhaill ED, Xu C, Fabozzo A, Padera R, Wasserman S, Freudenthal F, Ferreira LS, Langer R, Karp JM, del Nido PJ, Science Translational Medicine, 6, 218ra2 (2014)

[21] Pritchard CD, Arner KM, Neal RA, Neeley WL, Bojo P, Bachelder E, Holz J, Watson N, Botchwey EA, Langer RS, Ghosh FK, Biomaterials, 31, 2153 (2010)

[22] Sundback CA, Shyu JY, Wang Y, Faquin WC, Langer RS, Vacanti JP, Hadlock TA, Biomaterials, 26, 5454 (2005)

[23] Ifkovits JL, Devlin JJ, Eng G, Martens TP, Vunjak-Novakovic G, Burdick JA, ACS Appl. Mater. Interf., 1, 1878 (2009)

[24] Lee Y, Bae JW, Thi TTH, Park KM, Park KD, Chem. Commun., 51, 8876 (2015)

[25] Liang SL, Cook WD, Thouas GA, Chen QZ, Biomaterials, 31, 8516 (2010)

[26] Li Y, Huang W, Cook WD, Chen Q, Biomedical Mater., 8, 035006 (2013)

[27] Chen Q, Liang S, Thouas GA, Soft Matter, 7, 6484 (2011)

[28] Wu Y, Wang L, Guo B, Ma PX, J. Mater. Chem. B, 2, 3674 (2014)

[29] Patel A, Gaharwar AK, Iviglia G, Zhang H, Mukundan S, Mihaila SM, Demarchi D, Khademhosseini A, Biomaterials, 34, 3970 (2013)

[30] Nijst CLE, Bruggeman JP, Karp JM, Ferreira L, Zumbuehl A, Bettinger CJ, Langer R, Biomacromolecules, 8(10), 3067 (2007)

[31] Kurisawa M, Lee F, Wang LS, Chung JE, J. Mater. Chem., 20, 5371 (2010)

[32] Bae JW, Choi JH, Lee Y, Park KD, J. Tissue Eng. Reg. Medicine, 9, 1225 (2015)

[33] Kurisawa M, Chung JE, Yang YY, Gao SJ, Uyama H, Chem. Commun., 34, 4312 (2005)

[34] Jin R, Hiemstra C, Zhong Z, Feijen J, Biomaterials, 28, 2791 (2007)

[35] Park KM, Ko KS, Joung YK, Shin H, Park KD, J. Mater. Chem., 21, 13180 (2011)