Skip to main content
SpringerLink
Log in

Rapidly in situ forming adhesive hydrogel based on a PEG-maleimide modified polypeptide through Michael addition

  • Published:
Journal of Materials Science: Materials in Medicine Aims and scope Submit manuscript

Abstract

Polyethylene glycol-maleimide modified ε-polylysine (EPL-PEG-MAL) with a unique comb-shaped structure was designed and used as a novel crosslinker for thiolated chitosan (CSS). Novel polysaccharide/polypeptide bionic hydrogels based on CSS and EPL-PEG-MAL could form rapidly in situ within 1 min via Michael addition under physiological conditions. Rheological studies showed that introduction of PEG can dramatically improve the storage modulus (G′) of the hydrogels and the optimal hydrogel system showed superior G′ of 1,614 Pa. The maximum adhesion strength reached 148 kPa, six times higher than that of fibrin glue. Cytotoxicity test indicated that the hydrogel is nontoxic toward growth of L929 cells. Gelation time, swelling ratio, storage modulus and adhesion strength of the hydrogels can be modulated by the content of PEG-maleimide, CSS concentration and molar ratio of maleimide group to thiol group. Benefiting from the fast gelation behaviors, desirable mechanical properties, relatively high adhesive performance and no cytotoxicity, these hydrogels have the potential applications as promising biomaterials for tissue adhesion and sealing.

This is a preview of subscription content, log in via an institution to check access.

Access this article

Log in via an institution

Price excludes VAT (USA)
Tax calculation will be finalised during checkout.

Instant access to the full article PDF.

Institutional subscriptions

Fig. 1
Fig. 2
Fig. 3
Fig. 4
Fig. 5

Similar content being viewed by others

References

  1. Ishihara M, Nakanishi K, Ono K, Sato M, Kikuchi M, Saito Y, Yura H, Matsui T, Hattori H, Uenoyama M, Kurita A. Photocrosslinkable chitosan as a dressing for wound occlusion and accelerator in healing process. Biomaterials. 2002;23(3):833–40.

    Article  CAS  Google Scholar 

  2. Ono K, Ishihara M, Ozeki Y, Deguchi H, Sato M, Saito Y, Yura H, Sato M, Kikuchi M, Kurita A, Maehara T. Experimental evaluation of photocrosslinkable chitosan as a biologic adhesive with surgical applications. Surgery. 2001;130(5):844–50.

    Article  CAS  Google Scholar 

  3. Ogden S, Griffiths TW. A review of minimally invasive cosmetic procedures. Brit J Dermatol. 2008;159(5):1036–50.

    CAS  Google Scholar 

  4. Otani Y, Tabata Y, Ikada Y. Hemostatic capability of rapidly curable glues from gelatin, poly(l-glutamic acid), and carbodiimide. Biomaterials. 1998;19(22):2091–8.

    Article  CAS  Google Scholar 

  5. Anseth KS, Metters AT, Bryant SJ, Martens PJ, Elisseeff JH, Bowman CN. In situ forming degradable networks and their application in tissue engineering and drug delivery. J Control Release. 2002;78(1–3):199–209.

    Article  CAS  Google Scholar 

  6. Akgün A, Kuru S, Uraldi C, Tekin O, Karip B, Tug T, Öngören AU. Early effects of fibrin sealant on colonic anastomosis in rats: an experimental and case-control study. Tech Coloproctol. 2006;10(3):208–14.

    Article  Google Scholar 

  7. Lee MGM, Jones D. Applications of fibrin sealant in surgery. Surg Innov. 2005;12(3):203–13.

    Article  Google Scholar 

  8. Salameh JR, Schwartz JH, Hildebrandt DA. Can LigaSure seal and divide the small bowel. Am J Surg. 2006;191(6):791–3.

    Article  Google Scholar 

  9. Saygun O, Topaloglu S, Avsar FM, Ozel H, Hucumenoglu S, Sahin M, Hengirmen S. Reinforcement of the suture line with an ePTFE graft attached with histoacryl glue in duodenal trauma. Can J Surg. 2006;49(2):107–12.

    Google Scholar 

  10. Thetter O. Fibrin adhesive and its application in thoracic surgery. Thorac Cardiovasc Surg. 1981;29(5):290–2.

    Article  CAS  Google Scholar 

  11. Brennan M. Fibrin glue. Blood Rev. 1991;5:240–4.

    Article  CAS  Google Scholar 

  12. Tseng YC, Tabata Y, Hyon SH, Ikada Y. In vivo toxicity test of 2-cyanoacrylate polymers by cell culture method. J Biomed Mater Res. 1990;24(10):1355–67.

    Article  CAS  Google Scholar 

  13. Lämsä T, Jin HT, Sand J, Nordback I. Tissue adhesives and the pancreas: biocompatibility and adhesive properties of 6 preparations. Pancreas. 2008;36(3):261–6.

    Article  Google Scholar 

  14. Lee Y, Chung HJ, Yeo S, Ahn CH, Lee H, Messersmith PB, Park TG. Thermo-sensitive, injectable, and tissue adhesive sol-gel transition hyaluronic acid/pluronic composite hydrogels prepared from bio-inspired catechol-thiol reaction. Soft Matter. 2010;6(5):977–83.

    Article  CAS  Google Scholar 

  15. Masuko T, Minami A, Iwasaki N, Majima T, Nishimura SI, Lee YC. Thiolation of chitosan. Attachment of proteins via thioether formation. Biomacromolecules. 2005;6(2):880–4.

    Article  CAS  Google Scholar 

  16. Fakhry A, Schneider GB, Zaharias R, Senel S. Chitosan supports the initial attachment and spreading of osteoblasts preferentially over fibroblasts. Biomaterials. 2004;25(11):2075–9.

    Article  CAS  Google Scholar 

  17. Lauto A, Hook J, Doran M, Camacho F, Poole-Warren LA, Avolio A, Foster LJR. Chitosan adhesive for laser tissue repair: in vitro characterization. Laser Surg Med. 2005;36(3):193–201.

    Article  Google Scholar 

  18. Ono K, Saito Y, Yura H, Ishikawa K, Kurita A, Akaike T, Ishihara M. Photocrosslinkable chitosan as a biological adhesive. J Biomed Mater Res. 2000;49(2):289–95.

    Article  CAS  Google Scholar 

  19. Yamada K, Chen TH, Kumar G, Vesnovsky O, Topoleski LDT, Payne GF. Chitosan based water-resistant adhesive. Analogy to mussel glue. Biomacromolecules. 2000;1(2):252–8.

    Article  CAS  Google Scholar 

  20. Yamada K, Aoki T, Ikeda N, Hirata M. Application of enzymatically gelled chitosan solutions to water-resistant adhesives. J Appl Polym Sci. 2007;104(3):1818–27.

    Article  CAS  Google Scholar 

  21. Vernon B, Tirelli N, Bächi T, Haldimann D, Hubbell JA. Water-borne, in situ crosslinked biomaterials from phase-segregated precursors. J Biomed Mater Res. 2003;64A(3):447–56.

    Article  CAS  Google Scholar 

  22. Teng DY, Wu ZM, Zhang XG, Wang YX, Zheng C, Wang Z, Li CX. Synthesis and characterization of in situ cross-linked hydrogel based on self-assembly of thiol-modified chitosan with PEG diacrylate using Michael type addition. Polymer. 2010;51(3):639–46.

    Article  CAS  Google Scholar 

  23. Patterson J, Hubbell JA. SPARC-derived protease substrates to enhance the plasmin sensitivity of molecularly engineered PEG hydrogels. Biomaterials. 2011;32(5):1301–10.

    Article  CAS  Google Scholar 

  24. Hermanson GT. Bioconjugate techniques. 2nd ed. San Diego: Academic Press; 1996.

    Google Scholar 

  25. Phelps EA, Enemchukwu NO, Fiore VF, Sy JC, Murthy N, Sulchek TA, Barker TH, García AJ. Maleimide cross-linked bioactive PEG hydrogel exhibits improved reaction kinetics and cross-linking for cell encapsulation and in situ delivery. Adv Mater. 2012;24(1):64–70.

    Article  CAS  Google Scholar 

  26. Krauland AH, Hoffer MH, Bernkop-Schnürch A. Viscoelastic properties of a new in situ gelling thiolated chitosan conjugate. Drug Dev Ind Pharm. 2005;31(9):885–93.

    Article  CAS  Google Scholar 

  27. Shih IL, Shen MH, Van YT. Microbial synthesis of poly(ε-lysine) and its various applications. Bioresource Technol. 2006;97(9):1148–59.

    Article  CAS  Google Scholar 

  28. Gupta D, Tator CH, Shoichet MS. Fast-gelling injectable blend of hyaluronan and methylcellulose for intrathecal, localized delivery to the injured spinal cord. Biomaterials. 2006;27(11):2370–9.

    Article  CAS  Google Scholar 

  29. Wang T, Nie J, Yang DZ. Dextran and gelatin based photocrosslinkable tissue adhesive. Carbohydr Polym. 2012;90(4):1428–36.

    Article  CAS  Google Scholar 

  30. Li HB, Niu R, Yang JL, Nie J, Yang DZ. Photocrosslinkable tissue adhesive based on dextran. Carbohydr Polym. 2011;86(4):1578–85.

    Article  CAS  Google Scholar 

  31. Singh R. A sensitive assay for maleimide groups. Bioconjugate Chem. 1994;5(4):348–51.

    Article  CAS  Google Scholar 

  32. Yang C, Xu L, Zhou Y, Zhang XM, Huang X, Wang M, Han Y, Zhai ML, Wei SC, Li JQ. A green fabrication approach of gelatin/CM-chitosan hybrid hydrogel for wound healing. Carbohydr Polym. 2010;82(4):1297–305.

    Article  CAS  Google Scholar 

  33. Artzi N, Shazly T, Crespo C, Ramos AB, Chenault HK, Edelman ER. Characterization of star adhesive sealants based on PEG/dextran hydrogels. Macromol Biosci. 2009;9(8):754–65.

    Article  CAS  Google Scholar 

  34. Lutolf MP, Hubbell JA. Synthesis and physicochemical characterization of end-linked poly(ethylene glycol)-co-peptide hydrogels formed by Michael-type addition. Biomacromolecules. 2003;4:713–22.

    Article  CAS  Google Scholar 

  35. Sun JY, Zhao XH, Illeperuma WRK, Chaudhuri O, Oh KH, Mooney DJ, Vlassak JJ, Suo ZG. Highly stretchable and tough hydrogels. Nature. 2012;489:133–6.

    Article  CAS  Google Scholar 

  36. Naficy S, Brown HR, Razal JM, Spinks GM, Whitten PG. Progress toward robust polymer hydrogels. Aust J Chem. 2011;64(8):1007–25.

    Article  CAS  Google Scholar 

  37. Takaoka M, Nakamura T, Sugai H, Bentley AJ, Nakajima N, Fullwood NJ, Yokoi N, Hyon SH, Kinoshita S. Sutureless amniotic membrane transplantation for ocular surface reconstruction with a chemically defined bioadhesive. Biomaterials. 2008;29(19):2923–31.

    Article  CAS  Google Scholar 

  38. Hiemstra C, Van der Aa LJ, Zhong ZY, Dijkstra PJ, Feijen J. Rapidly in situ-forming degradable hydrogels from dextran thiols through Michael addition. Biomacromolecules. 2007;8(5):1548–56.

    Article  CAS  Google Scholar 

  39. Buwalda SJ, Dijkstra PJ, Feijen J. In situ forming poly(ethylene glycol)-poly(l-lactide) hydrogels via Michael addition: mechanical properties, degradation, and protein release. Macromol Chem Phys. 2012;213:766–75.

    Article  CAS  Google Scholar 

  40. Tournier EJM, Wallach J, Blond P. Sulfosuccinimidyl 4-(N-maleimidomethyl)-1-cyclohexane carboxylate as a bifunctional immobilization agent. Optimization of the coupling conditions. Anal Chim Acta. 1998;361(1–2):33–44.

    Article  CAS  Google Scholar 

  41. Mather BD, Viswanathan K, Miller KM, Long TE. Michael addition reactions in macromolecular design for emerging technologies. Prog Polym Sci. 2006;31(5):487–531.

    Article  CAS  Google Scholar 

  42. Nie W, Yuan XY, Zhao J, Zhou YL, Bao HJ. Rapidly in situ forming chitosan/ε-polylysine hydrogels for adhesive sealants and hemostatic materials. Carbohydr Polym. 2013;96:342–8.

    Article  CAS  Google Scholar 

  43. Serrero A, Trombotto S, Bayon Y, Gravagna P, Montanari S, David L. Polysaccharide-based adhesive for biomedical applications: correlation between rheological behavior and adhesion. Biomacromolecules. 2011;12(5):1556–66.

    Article  CAS  Google Scholar 

  44. Bernkop-Schnürch A, Weithaler A, Albrecht K, Greimel A. Thiomers: preparation and in vitro evaluation of a mucoadhesive nanoparticulate drug delivery system. Int J Pharm. 2006;317(1):76–81.

    Article  Google Scholar 

  45. Li ZH, DZ Y, Ma GP, Xu Q, Chen XM, Lu FM, Nie J. Synthesis and characterization of chitosan-based hydrogels. Int J Biol Macromol. 2009;44:121–7.

    Article  CAS  Google Scholar 

  46. Rabea EI, Badawy MET, Stevens CV, Smagghe G, Steurbaut W. Chitosan as antimicrobial agent: applications and mode of action. Biomacromolecules. 2003;4(6):1457–65.

    Article  CAS  Google Scholar 

Download references

Acknowledgments

The authors gratefully acknowledge the support for this research from the National Natural Science Foundation of China (Grant 51103095).

Author information

Authors and Affiliations

  1. School of Materials Science and Engineering, and Tianjin Key Laboratory of Composite and Functional Materials, Tianjin University, Tianjin, 300072, People’s Republic of China

    Yalin Zhou, Wei Nie, Jin Zhao & Xiaoyan Yuan

  2. Department of Polymer Materials, School of Materials Science and Engineering, Tianjin University, Tianjin, 300072, People’s Republic of China

    Jin Zhao

Authors
  1. Yalin Zhou
    View author publications

    You can also search for this author in PubMed Google Scholar

  2. Wei Nie
    View author publications

    You can also search for this author in PubMed Google Scholar

  3. Jin Zhao
    View author publications

    You can also search for this author in PubMed Google Scholar

  4. Xiaoyan Yuan
    View author publications

    You can also search for this author in PubMed Google Scholar

Corresponding author

Correspondence to Jin Zhao.

Electronic supplementary material

Below is the link to the electronic supplementary material.

Supplementary material 1 (DOCX 72 kb)

Rights and permissions

Reprints and permissions

About this article

Cite this article

Zhou, Y., Nie, W., Zhao, J. et al. Rapidly in situ forming adhesive hydrogel based on a PEG-maleimide modified polypeptide through Michael addition. J Mater Sci: Mater Med 24, 2277–2286 (2013). https://doi.org/10.1007/s10856-013-4987-1

Download citation

  • Received:

  • Accepted:

  • Published:

  • Issue Date:

  • DOI: https://doi.org/10.1007/s10856-013-4987-1

Keywords

Search

Navigation