Citation: Yi-Jie Zou, Shi-Sheng He, Jian-Zhong Du. ε-Poly(L-lysine)-based Hydrogels with Fast-acting and Prolonged Antibacterial Activities[J]. Chinese Journal of Polymer Science, ;2018, 36(11): 1239-1250. doi: 10.1007/s10118-018-2156-1 shu

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

a.
Department of Orthopedics, Shanghai Tenth People’s Hospital, Tongji University School of Medicine, Shanghai 200072, China
b.
Department of Polymeric Materials, School of Materials Science and Engineering, Key Laboratory of Advanced Department Civil Engineering Materials of Ministry of Education, Tongji University, Shanghai 201804, China

Corresponding author: Jian-Zhong Du, jzdu@tongji.edu.cn
Received Date: 1 May 2018
Revised Date: 4 May 2018
Accepted Date: 8 May 2018
Available Online: 11 June 2018

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.
- Chitosan,
- Poly(L-lysine),
- Hydrogel,
- Self-assembly,
- Antibacterial efficacy
1. [1]
  Il Kim, S. Bacterial infection after liver transplantation. World J. Gastroenterol. 2014, 20(20), 6211−6220 doi: 10.3748/wjg.v20.i20.6211
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), 1052−1056 doi: 10.1177/0009922811412949
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), 149−156 doi: 10.1038/nmat2915
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), 6255−6275 doi: 10.1039/C6CS00052E
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), 2872−2880 doi: 10.1021/bm200326g
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), 432−436 doi: 10.1039/C6NJ03260E
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), 1213−1223 doi: 10.1021/acs.biomac.6b00039
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), 119−128
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), 242−259 doi: 10.1177/0883911515610019
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), 6505−6517 doi: 10.1021/acsami.5b01234
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(N-epsilon-acryloyl L-lysine)/hyaluronic acid hydrogel as a mimic of the breast tumor microenvironment. Acta Biomater. 2016, 33, 131−141 doi: 10.1016/j.actbio.2016.01.027
12. [12]
  Cheng, C.; Zhang, X. L.; Meng, Y. B.; Zhang, Z. H.; Chen, J. D.; Zhang, Q. Q. Multiresponsive and biocompatible self-healing hydrogel: Its facile synthesis in water, characterization and properties. Soft Matter 2017, 13(16), 3003−3012 doi: 10.1039/C7SM00350A
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, 634379
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), 375−380 doi: 10.3136/fstr.17.375
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), 4154−4162 doi: 10.1021/acs.biomac.7b01209
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), 2704−2712 doi: 10.1016/j.biomaterials.2010.12.040
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), 2080−2086 doi: 10.1021/acs.biomac.6b00307
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), 16162 doi: 10.1038/nmicrobiol.2016.162
19. [19]
  Papenfort, K.; Bassler, B. L. Quorum sensing signal-response systems in gram-negative bacteria. Nat. Rev. Microbiol. 2016, 14(9), 576−588 doi: 10.1038/nrmicro.2016.89
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), 1807−1815 doi: 10.1016/j.biomaterials.2013.11.064
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, 286−294 doi: 10.1016/j.actbio.2014.10.043
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), 5463−5467 doi: 10.1002/adma.v22.48
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, 163−175 doi: 10.1038/nprot.2007.521
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), 2188−2194 doi: 10.1128/jb.171.4.2188-2194.1989
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−M97 doi: 10.1111/jfds.2013.78.issue-1
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.1028b00208 doi: 10.1021/acs.biomac.1028b00208
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 β-lactamase–producing Escherichia coli. J. Infect. Dis. 2011, 203(2), 273−282 doi: 10.1093/infdis/jiq029
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, 140−148 doi: 10.1016/j.colsurfb.2015.02.005
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), 7081−7089 doi: 10.1039/C4PY00868E
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), 4442−4455 doi: 10.1021/acsami.5b12141
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), 392−400 doi: 10.1016/j.ijpharm.2016.11.048
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), 2172−2181 doi: 10.1002/macp.v217.19
33. [33]
  Su, E.; Okay, O. Polyampholyte hydrogels formed via electrostatic and hydrophobic interactions. Eur. Polym. J. 2017, 88, 191−204 doi: 10.1016/j.eurpolymj.2017.01.029
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), 130−136 doi: 10.1111/ppa.2006.55.issue-1
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 doi: 10.1016/j.actbio.2015.10.036
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