Oxygen-generating alginate hydrogels as a bioactive acellular matrix for facilitating wound healing

Jeon Il Kang; Kyung Min Park; Ki Dong Park

Journal of Industrial and Engineering Chemistry, Vol.69, 397-404, January, 2019

DOI10.1016/j.jiec.2018.09.048 Export Citation

Oxygen-generating alginate hydrogels as a bioactive acellular matrix for facilitating wound healing

Jeon Il Kang, Kyung Min Park^†, and Ki Dong Park^{1, †}

Department of Bioengineering and Nano-Bioengineering, Incheon National University, Incheon 22012, Republic of Korea
¹Department of Molecular Science and Technology, Ajou University, Suwon 16499, Republic of Korea

E-mail:,

Although alginate-based hydrogels have been widely used as injectable matrices in a wide range of biomedical applications because of their biocompatibility and easy fabrication process, it isstill challenging to improve their bioactivity. Growing evidence has demonstrated that hyperoxic oxygen facilitates wound healing processes via transient oxidative stress. Herein, we report an oxygen- generating alginate (OGA) hydrogel as a bioactive acellular matrix for enhanced wound healing. We fabricate OGA hydrogels through calcium peroxide (CaO2)-mediated ionotropic interactions. The oxygen- releasing behavior of the hydrogels can be accurately controlled. Moreover, we demonstrate that the OGA hydrogels accelerated wound healing in full-thickness wounds in mice.

Keywords:Oxygen-generating biomaterials;Polymeric hydrogels;Wound healing;Tissue regenerative medicine

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[Referenced By]

[1] Ko DY, Shinde UP, Yeon B, Jeong B, Prog. Polym. Sci, 38, 672 (2013)

[2] Dimatteo R, Darling NJ, Segura T, Adv. Drug Deliv. Rev., 127, 167 (2018)

[3] Cho EJ, Sun B, Doh KO, Wilson EM, Torregrosa-Allen S, Elzey BD, Yeo Y, Biomaterials, 37, 312 (2015)

[4] Park KM, Gerecht S, Nat. Commun., 5, 4075 (2014)

[5] Amekan Y, Guntoro, Res. J. Pharm. Biol. Chem. Sci., 8, 1925 (2017)

[6] Lee KY, Rowley JA, Eiselt P, Moy EM, Bouhadir KH, Mooney DJ, Macromolecules, 33, 4291 (2000)

[7] Detsch R, Sarker B, Zehnder T, Frank G, Boccaccini AR, Mater. Today, 18, 590 (2015)

[8] Li M, Li H, Li X, Zhu H, Xu Z, Liu L, Ma J, Zhang M, ACS Appl. Mater. Interfaces, 9, 22160 (2017)

[9] Ho SS, Keown AT, Addison B, Leach JK, Biomacromolecules, 18(12), 4331 (2017)

[10] Semenza GL, Science, 318, 62 (2007)

[11] Covello KL, Simon MC, Curr. Top. Dev. Biol., 62, 37 (2004)

[12] Schreml S, Szeimies RM, Prantl L, Karrer S, Landthaler M, Babilas P, Br J. Dermatol., 163, 257 (2010)

[13] Zhang Q, Chang Q, Cox RA, Gong X, Gould LJ, J. Invest. Dermatol., 128, 2102 (2008)

[14] Thom SR, Bhopale VM, Velazquez OC, Goldstein LJ, Thom LH, Buerk DG, Am. J. Physiol. Heart Circ. Physiol., 290, H1378 (2006)

[15] Thom SR, Milovanova RN, Yang M, Bhopale VM, Sorokina EM, Uzun G, Malay DS, Troiano MS, Hardy KR, Lambert DS, Logue CJ, Margolis DJ, Wound Repair Regen., 19, 149 (2011)

[16] Schieber M, Chandel NS, Curr. Biol., 24, R453 (2014)

[17] Thom SR, J. Appl. Physiol., 106, 988 (2009)

[18] Gholipourmalekabadi M, Zhao S, Harrison BS, Mozafari M, Seifalian AM, Trends Biotechnol., 34, 1010 (2016)

[19] Oh SH, Ward CL, Atala A, Yoo JJ, Harrison BS, Biomaterials, 30, 757 (2009)

[20] Joiner A, J. Dent., 38, e17 (2010)

[21] Lu SG, Zhang X, Xue YF, J. Hazard. Mater., 337, 163 (2017)

[22] Poimenova A, Kitraki E, Kakaboura A, Rahiotis C, Dent. Mater., 34, e73 (2018)

[23] Alemdar N, Leijten J, Camci-Unal G, Hjortnaes J, Ribas J, Paul A, Mostafalu P, Gaharwar AK, Qiu YL, Sonkusale S, Liao RL, Khademhosseini A, ACS Biomater. Sci. Eng., 3, 1964 (2017)

[24] Newland B, Baeger M, Eigel D, Newland H, Werner C, ACS Biomater. Sci. Eng., 3, 787 (2017)

[25] Lee Y, Son JY, Kang JI, Park KM, Park KD, ACS Appl. Mater. Inter., 10, 18372 (2018)

[26] Lee Y, Choi KH, Park KM, Lee JM, Park BJ, Park KD, Acs Appl. Mater. Interfaces, 9, 16890 (2017)

[27] Lewis DM, Park KM, Eisinger-Mathason TSK, Simon C, Gerecht S, Proc. Natl. Acad. Sci. U. S. A., 77 (2017)

[28] Park KM, Blatchley MR, Gerecht S, Macromol. Rapid Commun., 35(22), 1968 (2014)

[29] Park KM, Gerecht S, Nat. Commun., 5 (2014)

[30] Fischer B, Bavister BD, J. Reprod. Fertil., 99, 673 (1993)

[31] Zhang Y, Wilson GS, Anal. Chim. Acta, 281, 513 (1993)

[32] Choi CA, Lee JE, Mazrad ZAI, In I, Jeong JH, Park SY, J. Ind. Eng. Chem., 63, 208 (2018)

[33] Kang EB, In IS, Lee KD, Park SY, J. Ind. Eng. Chem., 55, 224 (2017)

[34] Li H, Tan YJ, Leong KF, Li L, ACS Appl. Mater. Interfaces, 9, 20086 (2017)

[35] Sergeeva A, Feoktistova N, Prokopovic V, Gorin D, Volodkin D, Adv. Mater. Interfaces, 2 (2015)

[36] Pustlauk W, Paul B, Gelinsky M, Bernhardt A, Mater. Sci. Eng. C-Biomimetic Supramol. Syst., 64, 190 (2016)

[37] Straccia MC, d’Ayala GG, Romano I, Laurienzo P, Carbohydr. Polym., 125, 103 (2015)

[38] Breton-Romero R, Lamas S, Redox Biol., 2, 529 (2014)

[39] Ray PD, Huang BW, Tsuji Y, Cell. Signal., 24, 981 (2012)

[40] Kim YW, Byzova TV, Blood, 123, 625 (2014)

[41] Meng H, Li Y, Faust M, Konst S, Lee BP, Acta Biomater., 17, 160 (2015)

[42] Keilin D, Hartree E, Nature, 152, 626 (1943)

[43] Siqueira JF, Lopes HP, Int. Endod. J., 32, 361 (1999)

[44] Cohen G, Heikkila RE, J. Biol. Chem., 249, 2447 (1974)

[45] Grankvist K, Marklund S, Sehlin J, Taljedal IB, J. Biochem., 182, 17 (1979)