화학공학소재연구정보센터
Journal of Industrial and Engineering Chemistry, Vol.109, 372-383, May, 2022
Injectable gelatin-poly(ethylene glycol) adhesive hydrogels with highly hemostatic and wound healing capabilities
E-mail:,
Although numerous poly(ethylene glycol) (PEG)-based bioadhesives have been developed and commercialized for various biomedical applications, their biocompatibility and bioactivity performances are generally lacking. In addition, the development of adhesive hydrogels with rapid gelation and high tissue adhesion are desirable to promote the surgical procedures and enhance patient compliance. To overcome these problems, we designed a series of chemically crosslinked gelatin-PEG adhesive hydrogels (GP) through the enzymatic crosslinking reaction of horseradish peroxidase (HRP). The resultant GP hydrogels were rapidly formed in situ within seconds to minutes after injection, and their mechanical as well as adhesive properties were adjustable in a wide range by changing the molecular weight and content of PEG. Notably, the hybrid hydrogels composed of 20 kDa PEG with ratio of 2.5/7.5 gelatin/PEG (wt/wt) showed 11 times greater tissue adhesiveness than commercially available fibrin glues. From in vitro cell studies, the hybrid adhesive hydrogels are nontoxic and improve the cell proliferation. Importantly, the hydrogels exhibited excellent hemostatic capability and accelerated the wound healing in vivo, compared to fibrin glue. These injectable GP hydrogels effectively improved the tissue adhesiveness and bioactivity of PEG-based adhesives, and hold great potential for hemostatic and wound healing treatments.
  1. Ghobril C, Grinstaff MW, Chem. Soc. Rev., 44(7), 1820 (2015)
  2. Hong Y, Zhou F, Hua Y, Zhang X, Ni C, Pan D, Zhang Y, Jiang D, Yang L, Lin Q, Zou Y, Yu D, Arnot DE, Zou X, Zhu L, Zhang S, Ouyang H, Nat. Commun., 10, 2060 (2019)
  3. Zhang X, Ma Z, Ke Y, Xia YU, Xu X, Liu J, Gong Y, Shi Q, Yin J, Mater. Adv., 2, 5150 (2021)
  4. Lih E, Lee JS, Park KM, Park KD, Acta Biomater., 8, 3261 (2012)
  5. Kang JI, Park KM, Park KD, J. Ind. Eng. Chem., 69, 397 (2019)
  6. Lee Y, Bae JW, Oh DH, Park KM, Chun YW, Sung HJ, Park KD, J. Mater. Chem. B, 1, 2407 (2013)
  7. Wang R, Zhou B, Liu W, Feng XH, Li S, Yu DF, Chang JC, Chi B, Xu H, J. Biomater. Appl., 29, 1167 (2015)
  8. Ryu JH, Lee Y, Kong WH, Kim TG, Park TG, Lee H, Biomacromolecules, 12, 2653 (2011)
  9. Zhou Y, Nie W, Zhao J, Yuan X, J. Mater. Sci. -Mater. Med., 24, 2277 (2013)
  10. Li Y, Meng H, Liu Y, Narkar A, Lee BP, ACS Appl. Mater. Interfaces, 8, 11980 (2016)
  11. Park KM, Ko KS, Joung YK, Shin H, Park KD, J. Mater. Chem., 21, 13180 (2011)
  12. Liu Y, Meng H, Konst S, Sarmiento R, Rajachar R, Lee BP, ACS Appl. Mater. Interfaces, 6, 16982 (2014)
  13. Thi TTH, Lee JS, Lee Y, Park KM, Park KD, Macromol. Biosci., 16, 334 (2016)
  14. Liang J, Guo Z, Timmerman A, Grijpma D, Poot A, Biomed. Mater., 14, 024102 (2019)
  15. Zeng Z, Liu D, Li D, Mo X, Colloids Surf. B: Biointerfaces, 204, 111782 (2021)
  16. Brubaker CE, Messersmith PB, Biomacromolecules, 12, 4326 (2011)
  17. Carthew J, Frith JE, Forsythe JS, Truong VX, J. Mater. Chem. B, 6, 1394 (2018)
  18. Xu K, Cantu DA, Fu Y, Kim J, Zheng X, Hematti P, Kao WJ, Acta Biomater., 9, 8802 (2013)
  19. Teixeira LS, Feijen J, van Blitterswijk CA, Dijkstra PJ, Karperien M, Biomaterials, 33, 1281 (2012)
  20. Lee F, Bae KH, Kurisawa M, Biomed. Mater., 11, 014101 (2015)
  21. Bae JW, Choi JH, Lee Y, Park KD, J. Tissue Eng. Regen. Med., 9, 1225 (2015)
  22. Thi TTH, Lee Y, Thi PL, Park KD, J. Ind. Eng. Chem., 78, 34 (2019)
  23. Jung HY, Thi PL, HwangBo KH, Bae JW, Park KD, Carbohydr. Polym., 261, 117810 (2021)
  24. El-Sherbiny IM, Yacoub MH, Glob. Cardiol. Sci. Pract., 2013, 316 (2013)
  25. Wang YU, Wu YE, Long L, Yang LI, Fu D, Hu C, Kong Q, Wang Y, ACS Appl. Mater. Interfaces, 13, 33584 (2021)
  26. Kim MH, Lee JN, Lee J, Lee H, Park WH, ACS Biomater. Sci. Eng., 6, 3103 (2020)
  27. Zhu H, Mei X, He Y, Mao H, Tang W, Liu R, Yang J, Luo K, Gu Z, Zhou L, ACS Appl. Mater. Interface, 12, 4241 (2020)
  28. Lih E, Lee JS, Park KM, Park KD, Acta Biomater., 8, 3261 (2012)
  29. Wang R, Li J, Chen W, Xu T, Yun S, Xu Z, Xu Z, Sato T, Chi B, Xu H, Adv. Funct. Mater., 27, 1604894 (2017)
  30. Ziv-Polat O, Topaz M, Brosh T, Margel S, Biomaterials, 31, 741 (2010)
  31. Zhu L, Qiu J, Sakai E, RSC Adv., 7, 43755 (2017)
  32. Sun G, Zhang XZ, Chu CC, J. Mater. Sci. -Mater. Med., 19(8), 2865 (2008)
  33. Skotheim TA, Reynolds JR, Handbook of Conducting Polymers. Conjugated Polymers: Theory, Synthesis, Properties, and Characterization, CRC Press, Boca Raton, 2007.
  34. Tavafoghi M, Sheikhi A, Tutar R, Jahangiry J, Baidya A, Haghniaz R, Khademhosseini A, Adv. Healthc. Mater., 9, 1901722 (2020)
  35. He Z, Niu H, Zheng N, Liu S, Li Y, Polym. Chem., 10, 4789 (2019)
  36. Fujita AKL, da Rocha RW, Escobar A, de Nardi AB, Bagnato VS, de Menezes PFC, Correlation between Porcine and Human Skin Models by Optical Methods, Human Skin Cancers-Pathways, Mechanisms, Targets and Treatments, New York University Langone Medical Center, New York, 2018.
  37. Li Y, Meng H, Liu Y, Narkar A, Lee BP, ACS Appl. Mater. Interfaces, 8, 11980 (2016)
  38. Murphy JL, Vollenweider L, Xu F, Lee BP, Biomacromolecules, 11, 2976 (2010)
  39. Bhagat V, Becker ML, Biomacromolecules, 18, 3009 (2017)
  40. Li FJ, Liang JZ, Zhang SD, Zhu B, J. Polym. Environ., 23, 407 (2015)
  41. Park S, Park KM, Biomaterials, 182, 234 (2018)
  42. Wu SC, Chang WH, Dong GC, Chen KY, Chen YS, Yao CH, J. Bioact. Compat. Polym., 26, 565 (2011)