Advertisement

Chinese Journal of Polymer Science

, Volume 36, Issue 11, pp 1239–1250 | Cite as

ε-Poly(L-lysine)-based Hydrogels with Fast-acting and Prolonged Antibacterial Activities

  • Yi-Jie Zou
  • Shi-Sheng He
  • Jian-Zhong Du
Article

Abstract

Bacterial infections and the associated morbidity and mortality due to bacterial pathogens in wounds and medical implants have been increasing as most of current coatings cannot fulfill all the requirements including excellent intrinsically antibacterial activity, low cytotoxicity, and favorable physical properties. Herein, we present a kind of antibacterial hydrogel based on ε-poly(L-lysine) (EPL) grafted carboxymethyl chitosan (CMC-g-EPL) as the inherently antibacterial matrix and the surplus EPL as highly efficient antimicrobial agent. Such hydrogels possess tunable swelling abilities with water absorption percentages of 800%-2000% and modulus varying from 10 kPa to 100 kPa, and exhibit two-stage excellent antibacterial behavior. First, the free EPL can be released from the hydrogel network for quick and highly efficient bacteria killing with 99.99% of efficacy; second, the grafted EPL endows hydrogel matrix with prolonged intrinsically antibacterial activity, especially when most of free EPL is released from the hydrogel. Overall, we provide a new insight for preparing highly effective antibacterial hydrogels.

Keywords

Chitosan Poly(L-lysine) Hydrogel Self-assembly Antibacterial efficacy 

Preview

Unable to display preview. Download preview PDF.

Unable to display preview. Download preview PDF.

Notes

Acknowledgments

This work was financially supported by the National Natural Science Foundation of China (No. 21674081), Shanghai International Scientific Collaboration Fund (No. 15230724500), Shanghai 1000 Talents Plan (No. SH01068), and the Fundamental Research Fund for the Central Universities (Nos. 22120180109 and 1500219107).

Supplementary material

10118_2018_2156_MOESM1_ESM.pdf (396 kb)
ε-Poly(L-lysine)-based Hydrogels with Fast-acting and Prolonged Antibacterial Activities

References

  1. 1.
    Il Kim, S. Bacterial infection after liver transplantation. World J. Gastroenterol. 2014, 20(20), 6211–6220CrossRefGoogle Scholar
  2. 2.
    Yarden-Bilavsky, H.; Ashkenazi-Hoffnung, L.; Livni, G.; Amir, J.; Bilavsky, E. Month-by-month age analysis of the risk for serious bacterial infections in febrile infants with bronchiolitis. Clin. Pediatr. 2011, 50(11), 1052–1056CrossRefGoogle Scholar
  3. 3.
    Li, P.; Poon, Y. F.; Li, W. F.; Zhu, H. Y.; Yeap, S. H.; Cao, Y.; Qi, X. B.; Zhou, C. C.; Lamrani, M.; Beuerman, R. W.; Kang, E. T.; Mu, Y. G.; Li, C. M.; Chang, M. W.; Leong, S. S. J.; Chan-Park, M. B. A polycationic antimicrobial and biocompatible hydrogel with microbe membrane suctioning ability. Nat. Mater. 2011, 10(2), 149–156CrossRefPubMedGoogle Scholar
  4. 4.
    Huang, Q. T.; Zou, Y. J.; Arno, M. C.; Chen, S.; Wang, T.; Gao, J. Y.; Dove, A. P.; Du, J. Z. Hydrogel scaffolds for differentiation of adipose-derived stem cells. Chem. Soc. Rev. 2017, 46(20), 6255–6275CrossRefPubMedGoogle Scholar
  5. 5.
    Tran, N. Q.; Joung, Y. K.; Lih, E.; Park, K. D. In situ forming and Rutin-releasing chitosan hydrogels as injectable dressings for dermal wound healing. Biomacromolecules 2011, 12(8), 2872–2880CrossRefPubMedGoogle Scholar
  6. 6.
    Lu, Z. T.; Zhang, J. Q.; Yu, Z. G.; Liu, Q. Z.; Liu, K.; Li, M. F.; Wang, D. Hydrogel degradation triggered by pH for the smart release of antibiotics to combat bacterial infection. New J. Chem. 2017, 41(2), 432–436CrossRefGoogle Scholar
  7. 7.
    Ghavaminejad, A.; Park, C. H.; Kim, C. S. In situ synthesis of antimicrobial silver nanoparticles within antifouling zwitterionic hydrogels by catecholic redox chemistry for wound healing application. Biomacromolecules 2016, 17(3), 1213–1223CrossRefPubMedGoogle Scholar
  8. 8.
    Song, T.; Xi, Y. J.; Du, J. Z. Antibacterial hydrogels incorporated with poly(glutamic acid)-based vesicles. Acta Polymerica Sininca (in Chinese) 2018, (1), 119–128Google Scholar
  9. 9.
    Wang, R.; Zhou, B.; Xu, D. L.; Xu, H.; Liang, L.; Feng, X. H.; Ouyang, P. K.; Chi, B. Antimicrobial and biocompatible epsilon-polylysine-gamma-poly(glutamic acid)-based hydrogel system for wound healing. J. Bioact. Compat. Polym. 2016, 31(3), 242–259CrossRefGoogle Scholar
  10. 10.
    Shu, Y.; Hao, T.; Yao, F. L.; Qian, Y. F.; Wang, Y.; Yang, B. G.; Li, J. J.; Wang, C. Y. RoY peptide-modified chitosan-based hydrogel to improve angiogenesis and cardiac repair under hypoxia. ACS Appl. Mater. Interfaces 2015, 7(12), 6505–6517CrossRefPubMedGoogle Scholar
  11. 11.
    Xu, W. J.; Qian, J. M.; Zhang, Y. P.; Suo, A. L.; Cui, N.; Wang, J. L.; Yao, Y.; Wang, H. J. A double-network poly(jVepsilon-acryloyl L-lysine)/hyaluronic acid hydrogel as a mimic of the breast tumor microenvironment. Acta Biomater. 2016, 33, 131–141CrossRefPubMedGoogle Scholar
  12. 12.
    Cheng, C.; Zhang, X. L.; Meng, Y. B.; Zhang, Z. H.; Chen, J. D.; Zhang, Q. Q. Multiresponsive and biocompatible selfhealing hydrogel: Its facile synthesis in water, characterization and properties. Soft Matter 2017, 13(16), 3003–3012CrossRefPubMedGoogle Scholar
  13. 13.
    Togo, Y.; Takahashi, K.; Saito, K.; Kiso, H.; Huang, B. Y.; Tsukamoto, H.; Hyon, S. H.; Bessho, K. Aldehyded dextran and epsilon-poly(L-lysine) hydrogel as nonviral gene carrier. Stem Cells Int. 2013, 634379Google Scholar
  14. 14.
    Unalan, I. U.; Ucar, K. D. A.; Arcan, I.; Korel, F.; Yemenicioglu, A. Antimicrobial potential of polylysine in edible films. Food Sci. Technol. Res. 2011, 17(4), 375–380CrossRefGoogle Scholar
  15. 15.
    Zhou, C. C.; Yuan, Y.; Zhou, P. Y.; Wang, F. Y. K.; Hong, Y. X.; Wang, N. S.; Xu, S. G.; Du, J. Z. Highly effective antibacterial vesicles based on peptide-mimetic alternating copolymers for bone repair. Biomacromolecules 2017, 18(12), 4154–4162CrossRefPubMedGoogle Scholar
  16. 16.
    Zhou, C. C.; Li, P.; Qi, X. B.; Sharif, A. R. M.; Poon, Y. F.; Cao, Y.; Chang, M. W.; Leong, S. S. J.; Chan-Park, M. B. A photopolymerized antimicrobial hydrogel coating derived from epsilon-poly-L-lysine. Biomaterials 2011, 32(11), 2704–2712CrossRefPubMedGoogle Scholar
  17. 17.
    Gao, J. Y.; Wang, M. Z.; Wang, F. Y. K.; Du, J. Z. Synthesis and mechanism insight of a peptide-grafted hyperbranched polymer nanosheet with weak positive charges but excellent intrinsically antibacterial efficacy. Biomacromolecules 2016, 17(6), 2080–2086CrossRefPubMedGoogle Scholar
  18. 18.
    Lam, S. J.; O’Brien-Simpson, N. M.; Pantarat, N.; Sulistio, A.; Wong, E. H. H.; Chen, Y. Y.; Lenzo, J. C.; Holden, J. A.; Blencowe, A.; Reynolds, E. C.; Qiao, G. G. Combating multidrug-resistant gram-negative bacteria with structurally nanoengineered antimicrobial peptide polymers. Nat. Microbiol. 2016, 1(11), 16162CrossRefPubMedGoogle Scholar
  19. 19.
    Papenfort, K.; Bassler, B. L. Quorum sensing signal-response systems in gram-negative bacteria. Nat. Rev. Microbiol. 2016, 14(9), 576–588CrossRefPubMedPubMedCentralGoogle Scholar
  20. 20.
    Tong, X. M.; Yang, F. Engineering interpenetrating network hydrogels as biomimetic cell niche with independently tunable biochemical and mechanical properties. Biomaterials 2014, 35(6), 1807–1815CrossRefPubMedGoogle Scholar
  21. 21.
    Edwards, S. L.; Ulrich, D.; White, J. F.; Su, K.; Rosamilia, A.; Ramshaw, J. A. M.; Gargett, C. E.; Werkmeister, J. A. Temporal changes in the biomechanical properties of endometrial mesenchymal stem cell seeded scaffolds in a rat model. Acta Biomater. 2015, 13, 286–294CrossRefPubMedGoogle Scholar
  22. 22.
    Lv, M.; Su, S.; He, Y.; Huang, Q.; Hu, W.; Li, D.; Fan, C.; Lee, S. T. Long-term antimicrobial effect of silicon nanowires decorated with silver nanoparticles. Adv. Mater. 2010, 22(48), 5463–5467CrossRefPubMedGoogle Scholar
  23. 23.
    Wiegand, I.; Hilpert, K.; Hancock, R. E. W. Agar and broth dilution methods to determine the minimal inhibitory concentration (MIC) of antimicrobial substances. Nat. Protoc. 2008, 3, 163–175CrossRefPubMedGoogle Scholar
  24. 24.
    Dahl, T. A.; Midden, W. R.; Hartman, P. E. Comparison of killing of Gram-negative and Gram-positive bacteria by pure singlet oxygen. J. Bacteriol. 1989, 171(4), 2188–2194CrossRefPubMedPubMedCentralGoogle Scholar
  25. 25.
    Geng, X. D.; Yang, R. H.; Huang, J. Y.; Zhang, X.; Wang, X. Y. Evaluation antibacterial activity of quaternary-based chitin/chitosan derivatives in vitro. J. Food Sci. 2013, 78(1), M90–M97CrossRefPubMedGoogle Scholar
  26. 26.
    Sun, H.; Hong, Y. X.; Xi, Y. J.; Zou, Y. J.; Gao, J. Y.; Du, J. Z. Synthesis, self-assembly and biomedical applications of antimicrobial peptide-polymer conjugates. Biomacromolecules 2018, 10.1021/acs.biomac.1028b00208Google Scholar
  27. 27.
    Zheng, H.; Lu, J.; Chao, F.; Ying, Z.; Hui, B.; Zhang, X.; Xue, X.; Chen, Y.; Luo, X. Underlying mechanism of in vivo and in vitro activity of c-terminal-amidated thanatin against clinical isolates of extended-spectrum-lactamase-producing Escherichia coli. J. Infect. Dis. 2011, 203(2), 273–282CrossRefGoogle Scholar
  28. 28.
    Liu, Z. Q.; Wei, Z.; Zhu, X. L.; Huang, G. Y.; Xu, F.; Yang, J. H.; Osada, Y.; Zrinyi, M.; Li, J. H.; Chen, Y. M. Dextran-based hydrogel formed by thiol-Michael addition reaction for 3D cell encapsulation. Colloids Surf., B 2015, 128, 140–148CrossRefGoogle Scholar
  29. 29.
    Zhou, L.; Chen, M.; Guan, Y.; Zhang, Y. J. Multiple responsive hydrogel films based on dynamic schiff base linkages. Polym. Chem. 2014, 5(24), 7081–7089CrossRefGoogle Scholar
  30. 30.
    Dong, D. Y.; Li, J. J.; Cui, M.; Wang, J. M.; Zhou, Y. H.; Luo, L.; Wei, Y. F.; Ye, L.; Sun, H.; Yao, F. L. In situ “clickable” zwitterionic starch-based hydrogel for 3D cell encapsulation. ACS Appl. Mater. Interfaces 2016, 8(7), 4442–4455CrossRefPubMedGoogle Scholar
  31. 31.
    Ishii-Mizuno, Y.; Umeki, Y.; Onuki, Y.; Watanabe, H.; Takahashi, Y.; Takakura, Y.; Nishikawa, M. Improved sustained release of antigen from immunostimulatory DNA hydrogel by electrostatic interaction with chitosan. Int. J. Pharm. 2017, 516(1-2), 392–400CrossRefPubMedGoogle Scholar
  32. 32.
    Zhang, G. Z.; Ngai, T.; Deng, Y. H.; Wang, C. Y. An injectable hydrogel with excellent self-healing property based on quadruple hydrogen bonding. Macromol. Chem. Phys. 2016, 217(19), 2172–2181CrossRefGoogle Scholar
  33. 33.
    Su, E.; Okay, O. Polyampholyte hydrogels formed via electrostatic and hydrophobic interactions. Eur. Polym. J. 2017, 88, 191–204CrossRefGoogle Scholar
  34. 34.
    Sakamoto, J. M.; Gordon, T. R. Factors influencing infection of mechanical wounds by Fusarium circinatum on Monterey pines (pinus radiata). Plant Pathol. 2006, 55(1), 130–136CrossRefGoogle Scholar
  35. 35.
    Toda, H.; Yamamoto, M.; Uyama, H.; Tabata, Y. Fabrication of hydrogels with elasticity changed by alkaline phosphatase for stem cell culture. Acta Biomater. 2016, 29, 215–227.CrossRefPubMedGoogle Scholar

Copyright information

© Chinese Chemical Society, Institute of Chemistry, Chinese Academy of Sciences and Springer-Verlag GmbH Germany, part of Springer Nature 2018

Authors and Affiliations

  1. 1.Department of Orthopedics, Shanghai Tenth People’s HospitalTongji University School of MedicineShanghaiChina
  2. 2.Department of Polymeric Materials, School of Materials Science and Engineering, Key Laboratory of Advanced Department Civil Engineering Materials of Ministry of EducationTongji UniversityShanghaiChina

Personalised recommendations