Dopa-Empowered Schiff Base Forming Alginate Hydrogel Glue for Rapid Hemostatic Control

Chung Kil Song; Min-Kyoung Kim; Junghan Lee; Enkhzaya Davaa; Rengarajan Baskaran; Su-Geun Yang

Macromolecular Research, Vol.27, No.2, 119-125, February, 2019

DOI10.1007/s13233-019-7026-3 Export Citation

Dopa-Empowered Schiff Base Forming Alginate Hydrogel Glue for Rapid Hemostatic Control

Chung Kil Song, Min-Kyoung Kim, Junghan Lee, Enkhzaya Davaa, Rengarajan Baskaran, and Su-Geun Yang^†

WCSL, Department of New Drug Development, Inha University College of Medicine, B-308, Chungsuk Bldg, 366, Seohae-Daero, Jung-Gu, Incheon 22332, Korea

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In this study we prepared tissue-adhesive hemostatic glue and assessed hemostatic effects on hepatic bleeding animal model. Alginate was used as primary polymer for the fabrication of hemostatic glue, oxidized for the introduction of the tissue-adhesive Schiff base forming aldehyde and then encoded with mussel-inspired dopa. In addition, polyallylamine (PAA) was selected for as an intra-structuring polymer which ensures the gel strength and allows instantaneous glue formation on the bleeding spot. Primary glue (OA glue) was quickly formed within 5 to 10 seconds after the mixing oxidized alginate (OA) with PAA. The degree of oxidation and the mixing ratio of OA and PAA were precisely determined based on glue formation time and gel strength. And the extend of dopa conjugation on OA was determined by the tissue adhesion force and the elasticity of the glue (Dopa-OA glue). Especially, elasticity of Dopa-OA glue was significantly enhanced after introduction of dopa to OA. Functional assay of Dopa-OA glue on hepatic bleeding animal model showed much enhanced hemostatic action. Dopa-OA glue is expected to provide novel injectable tissue adhesives for the treatment of hemorrhage caused by clinical procedures or trauma.

Keywords:alginate;hemostatic glue;schiff base;dopa;tissue adhesive

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Hong S, Yang K, Kang B, Lee C, Song IT, Byun E, Park KI, Cho SW, Lee H, Adv. Funct. Mater., 23(14), 1774 (2013)

[Referenced By]

[1] Kelly JF, Ritenour AE, McLaughlin DF, Bagg KA, Apodaca AN, Mallak CT, Pearse L, Lawnick MM, Champion HR, Holcomb JB, J. Trauma, 64, S21 (2008)

[2] Montanaro L, Arciola CR, Cenni E, Ciapetti G, Savioli F, Filippini F, Barsanti LA, Biomaterials, 22, 59 (2001)

[3] Ferreira P, Pereira R, Coelho JFJ, Silva AFM, Gil MH, Int. J. Biol. Macromol., 40, 144 (2007)

[4] Toriumi DM, O'Grady K, Desai D, Bagal A, Plast. Reconstr. Surg., 102, 2209 (1998)

[5] Canonico S, Acta Biomed., 74, Supple 2:21 (2003).

[6] Siedentop KH, Park JJ, Shah AN, Bhattacharyya TK, O'Grady KM, Am. J. Otolaryngol., 22, 230 (2001)

[7] Bitton R, Bianco-Peled H, Macromol. Biosci., 8, 393 (2008)

[8] Jeon O, Samorezov JE, Alsberg E, Acta Biomater., 10, 47 (2014)

[9] Lansdown AB, Payne MJ, J. R. Coll. Surg. Edinb., 39, 284 (1994)

[10] Sank A, Chi M, Shima T, Reich R, Martin GR, Surgery, 106, 1141 (1989)

[11] Gao CM, Liu MZ, Chen J, Zhang X, Polym. Degrad. Stabil., 94, 1405 (2009)

[12] Bouhadir KH, Lee KY, Alsberg E, Damm KL, Anderson KW, Mooney DJ, Biotechnol. Prog., 17(5), 945 (2001)

[13] Balakrishnan B, Jayakrishnan A, Biomaterials, 26, 3941 (2005)

[14] Ryu JH, Lee Y, Kong WH, Kim TG, Park TG, Lee H, Biomacromolecules, 12(7), 2653 (2011)

[15] Baik SH, Kim JH, Cho HH, Park SN, Kim YS, Suh H, J. Surg. Res., 164, E221 (2010)

[16] Lee Y, Chung HJ, Yeo S, Ahn CH, Lee H, Messersmith PB, Park TG, Soft Matter, 6, 977 (2010)

[17] Zhao H, Heindel ND, Pharm. Res., 8, 400 (1991)

[18] Mo XM, Iwata H, Matsuda S, Ikada Y, J. Biomater. Sci. Polym. Ed., 11, 341 (2000)

[19] Jones D,S Irwin CR, Woolfson AD, Djokic J, Adams V, J. Pharm. Sci., 88, 592 (1999)

[20] Jones DS, Woolfson AD, Brown AF, Coulter WA, McClelland C, Irwin CR, J. Control. Release, 67, 357 (2000)

[21] Jones DS, Bruschi ML, de Freitas O, Gremiao MPD, Lara EHG, Andrews GP, Int. J. Pharm., 372, 49 (2009)

[22] Murakami Y, Yokoyama M, Nishida H, Tomizawa Y, Kurosawa H, Colloids Surf. B: Biointerfaces, 65, 186 (2008)

[23] Murakami Y, Yokoyama M, Nishida H, Tomizawa Y, Kurosawa H, J. Biomed. Mater. Res. Part B: Appl. Biomater., 91B, 102 (2009)

[24] Ferry JD, Fitzgerald ER, Grand LD, Williams ML, Ind. Eng. Chem., 44, 703 (1952)

[25] Hong S, Yang K, Kang B, Lee C, Song IT, Byun E, Park KI, Cho SW, Lee H, Adv. Funct. Mater., 23(14), 1774 (2013)