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A Glycosylated and Catechol-crosslinked ε-Polylysine Hydrogel: Simple Preparation and Excellent Wound Hemostasis and Healing Properties

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Abstract

Commercial tissue adhesives have been widely applied in wound hemostats and dressings while enhancing the hemostasis and healing capabilities is challenging to meet clinical needs. Herein, we designed the glucose- and catechol-functionalized derivatives from commercial ε-polylysine (EPL) and prepared the hydrogels by simple amidation and catechol-crosslinking reactions, which have larger swelling ratios of 220%–240%, suitable microporous size of about 6–8 µm, and tissue adhesion strength of about 20–40 kPa. The hemolysis, cytotoxicity, and cellular double-staining assays indicate that those hydrogels had good biocompatibility and the H-3 hydrogel with higher glucose content gave a lower hemolysis ratio of 0.73%±0.14%. The blood-clotting index, blood cell attachment and adhesion studies showed those hydrogels had fast blood-coagulation, resulting in excellent hemostasis performance with a short hemostatic time of 38–46 s and less blood loss of 19%–34% in a liver hemorrhage model. A full-thickness rat-skin defect model further demonstrates that the H-3 hydrogel achieved fast wound healing with a wound closure of 70.0%±2.7% on postoperative day 7 and nearly full closure on day 14. Remarkably, the hydroproline level that denotes the collagen production reached a higher one of 7.24±0.55 µg/mg comparable to that in normal skins on day 14, evidencing the wound healing was close to completion in the H-3 treatment. Consequently, this work provides a simple method to construct a glycosylated and catechol-functionalized hydrogel platform from commercial EPL, holding translational potentials in wound hemostats and dressings.

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References

  1. Zhao, Y.; Song, S.; Ren, X.; Zhang, J.; Lin, Q.; Zhao, Y. Supramolecular adhesive hydrogels for tissue engineering applications. Chem. Rev. 2022, DOI: https://doi.org/10.1021/acs.chemrev.1c00815.

  2. Zuo, X. L.; Wang, S. F.; Le, X. X.; Lu, W.; Chen, T. Self-healing polymeric hydrogels: toward multifunctional soft smart materials. Chinese J. Polym. Sci. 2021, 39, 1262–1280.

    Article  CAS  Google Scholar 

  3. Chen, K.; Wu, Z.; Liu, Y.; Yuan, Y.; Liu, C. Injectable double-crosslinked adhesive hydrogels with high mechanical resilience and effective energy dissipation for joint wound treatment. Adv. Funct. Mater. 2022, DOI: https://doi.org/10.1002/adfm.202109687.

  4. Pourshahrestani, S.; Zeimaran, E.; Kadri, N. A.; Mutlu, N.; Boccaccini, A. R. Polymeric hydrogel systems as emerging biomaterial platforms to enable hemostasis and wound healing. Adv. Healthc. Mater. 2020, 9, e2000905.

    Article  Google Scholar 

  5. Nam, S.; Mooney, D. Polymeric tissue adhesives. Chem. Rev. 2021, 121, 11336–11384.

    Article  CAS  Google Scholar 

  6. Zhang, K.; Chen, X.; Xue, Y.; Lin, J.; Liang, X.; Zhang, J.; Zhang, J.; Chen, G.; Cai, C.; Liu, J. Tough hydrogel bioadhesives for sutureless wound sealing, hemostasis and biointerfaces. Adv. Funct. Mater. 2022, DOI: https://doi.org/10.1002/adfm.202111465.

  7. Yuk, H.; Varela, C. E.; Nabzdyk, C. S.; Mao, X.; Padera, R. F.; Roche, E. T.; Zhao, X. Dry double-sided tape for adhesion of wet tissues and devices. Nature 2019, 575, 169–174.

    Article  CAS  Google Scholar 

  8. Wang, R.; Li, J.; Chen, W.; Xu, T.; Yun, S.; Xu, Z.; Xu, Z.; Sato, T.; Chi, B.; Xu, H. A biomimetic mussel-inspired ε-poly-l-lysine hydrogel with robust tissue-anchor and anti-infection capacity. Adv. Funct. Mater. 2017, 27, 1604894.

    Article  Google Scholar 

  9. Bai, Q.; Teng, L.; Zhang, X.; Dong, C. M. Multifunctional single-component polypeptide hydrogels: the gelation mechanism, superior biocompatibility, high performance hemostasis, and scarless wound healing. Adv. Healthc. Mater. 2022, 11, e2101809.

    Article  Google Scholar 

  10. Teng, L.; Shao, Z.; Bai, Q.; Zhang, X.; He, Y. S.; Lu, J.; Zou, D.; Feng, C.; Dong, C. M. Biomimetic glycopolypeptide hydrogels with tunable adhesion and microporous structure for fast hemostasis and highly efficient wound healing. Adv. Funct. Mater. 2021, 31, 2105628.

    Article  CAS  Google Scholar 

  11. Wu, S. J.; Yuk, H.; Wu, J.; Nabzdyk, C. S.; Zhao, X. A Multifunctional origami patch for minimally invasive tissue sealing. Adv. Mater. 2021, 33, e2007667.

    Article  Google Scholar 

  12. Yuk, H.; Wu, J.; Sarrafian, T. L.; Mao, X.; Varela, C. E.; Roche, E. T.; Griffiths, L. G.; Nabzdyk, C. S.; Zhao, X. Rapid and coagulation-independent haemostatic sealing by a paste inspired by barnacle glue. Nat. Biomed. Eng. 2021, 5, 1131–1142.

    Article  CAS  Google Scholar 

  13. Shi, J.; Yu, L.; Ding, J. PEG-based thermosensitive and biodegradable hydrogels. Acta Biomater. 2021, 128, 42–59.

    Article  CAS  Google Scholar 

  14. Wang, Y. Q.; Dou, X. Y.; Wang, H. F.; Wang, X.; Wu, D. C. Dendrimer-based hydrogels with controlled drug delivery property for tissue adhesion. Chinese J. Polym. Sci. 2021, 39, 1421–1430.

    Article  CAS  Google Scholar 

  15. Xue, B.; Gu, J.; Li, L.; Yu, W.; Yin, S.; Qin, M.; Jiang, Q.; Wang, W.; Cao, Y. Hydrogel tapes for fault-tolerant strong wet adhesion. Nat. Commun. 2021, 12, 7156.

    Article  CAS  Google Scholar 

  16. Fichman, G.; Andrews, C.; Patel, N. L.; Schneider, J. P. Antibacterial gel coatings inspired by the cryptic function of a mussel byssal peptide. Adv. Mater. 2021, 33, e2103677.

    Article  Google Scholar 

  17. Liang, Y.; Li, Z.; Huang, Y.; Yu, R.; Guo, B. Dual-dynamic-bond cross-linked antibacterial adhesive hydrogel sealants with on-demand removability for post-wound-closure and infected wound healing. ACS Nano 2021, 15, 7078–7093.

    Article  CAS  Google Scholar 

  18. Ma, C.; Sun, J.; Li, B.; Feng, Y.; Sun, Y.; Xiang, L.; Wu, B.; Xiao, L.; Liu, B.; Petrovskii, V. S.; Bin, L.; Zhang, J.; Wang, Z.; Li, H.; Zhang, L.; Li, J.; Wang, F.; Gstl, R.; Potemkin, II; Chen, D.; Zeng, H.; Zhang, H.; Liu, K.; Herrmann, A. Ultra-strong bio-glue from genetically engineered polypeptides. Nat. Commun. 2021, 12, 3613.

    Article  CAS  Google Scholar 

  19. Bevilacqua, M. P.; Huang, D. J.; Wall, B. D.; Lane, S. J.; Edwards, C. K., 3rd; Hanson, J. A.; Benitez, D.; Solomkin, J. S.; Deming, T. J. Amino acid block copolymers with broad antimicrobial activity and barrier properties. Macromol. Biosci. 2017, 17, 1600492.

    Article  Google Scholar 

  20. Xu, W. K.; Tang, J. Y.; Yuan, Z.; Cai, C. Y.; Chen, X. B.; Cui, S. Q.; Liu, P.; Yu, L.; Cai, K. Y.; Ding, J. D. Accelerated cutaneous wound healing using an injectable teicoplanin-loaded PLGA-PEG-PLGA thermogel dressing. Chinese J. Polym. Sci. 2019, 37, 548–559.

    Article  CAS  Google Scholar 

  21. Lu, D.; Wang, H.; Li, T. e.; Li, Y.; Wang, X.; Niu, P.; Guo, H.; Sun, S.; Wang, X.; Guan, X.; Ma, H.; Lei, Z. Versatile surgical adhesive and hemostatic materials: synthesis, properties, and application of thermoresponsive polypeptides. Chem. Mater. 2017, 29, 5493–5503.

    Article  CAS  Google Scholar 

  22. Li, S.; Chen, N.; Li, X.; Li, Y.; Xie, Z.; Ma, Z.; Zhao, J.; Hou, X.; Yuan, X. Bioinspired double-dynamic-bond crosslinked bioadhesive enables post-wound closure care. Adv. Funct. Mater. 2020, 20, 2000130.

    Article  Google Scholar 

  23. Bonduelle, C.; Lecommandoux, S. Synthetic glycopolypeptides as biomimetic analogues of natural glycoproteins. Biomacromolecules 2013, 14, 2973–2983.

    Article  CAS  Google Scholar 

  24. Parani, M.; Lokhande, G.; Singh, A.; Gaharwar, A. K. Engineered nanomaterials for infection control and healing acute and chronic wounds. ACS Appl. Mater. Interfaces 2016, 8, 10049–10069.

    Article  CAS  Google Scholar 

  25. Gao, Y.; Li, Z.; Huang, J.; Zhao, M.; Wu, J. In situ formation of injectable hydrogels for chronic wound healing. J. Mater. Chem. B 2020, 8, 8768–8780.

    Article  CAS  Google Scholar 

  26. Wang, D.; Yang, X.; Liu, Q.; Yu, L.; Ding, J. Enzymatically cross-linked hydrogels based on a linear poly(ethylene glycol) analogue for controlled protein release and 3D cell culture. J. Mater. Chem. B 2018, 6, 6067–6079.

    Article  CAS  Google Scholar 

  27. Ren, K.; Li, B.; Xu, Q.; Xiao, C.; He, C.; Li, G.; Chen, X. Enzymatically crosslinked hydrogels based on linear poly(ethylene glycol) polymer: performance and mechanism. Polym. Chem. 2017, 8, 7017–7024.

    Article  CAS  Google Scholar 

  28. Zhang, K.; Feng, Q.; Fang, Z.; Gu, L.; Bian, L. Structurally dynamic hydrogels for biomedical applications: pursuing a fine balance between macroscopic stability and microscopic dynamics. Chem. Rev. 2021, 121, 11149–11193.

    Article  CAS  Google Scholar 

  29. Poustchi, F.; Amani, H.; Ahmadian, Z.; Niknezhad, S. V.; Mehrabi, S.; Santos, H. A.; Shahbazi, M. A. Combination therapy of killing diseases by injectable hydrogels: from concept to medical applications. Adv. Healthc. Mater. 2020, 10, 2001571.

    Article  Google Scholar 

  30. Guo, B.; Dong, R.; Liang, Y.; Li, M. Haemostatic materials for wound healing applications. Nat. Rev. Chem. 2021, 5, 773–791.

    Article  CAS  Google Scholar 

  31. Huang, Y.; Zhao, X.; Zhang, Z.; Liang, Y.; Yin, Z.; Chen, B.; Bai, L.; Han, Y.; Guo, B. Degradable gelatin-based IPN cryogel hemostat for rapidly stopping deep noncompressible hemorrhage and simultaneously improving wound healing. Chem. Mater. 2020, 32, 6595–6610.

    Article  CAS  Google Scholar 

  32. Yu, J.; Wang, K.; Fan, C.; Zhao, X.; Gao, J.; Jing, W.; Zhang, X.; Li, J.; Li, Y.; Yang, J.; Liu, W. An ultrasoft self-fused supramolecular polymer hydrogel for completely preventing postoperative tissue adhesion. Adv. Mater. 2021, 33, 2008395.

    Article  CAS  Google Scholar 

  33. Cui, C.; Liu, W. Recent advances in wet adhesives: adhesion mechanism, design principle and applications. Prog. Polym. Sci. 2021, 116, 101388.

    Article  CAS  Google Scholar 

  34. Maleki, A.; He, J.; Bochani, S.; Nosrati, V.; Shahbazi, M. A.; Guo, B. Multifunctional photoactive hydrogels for wound healing acceleration. ACS Nano 2021, 15, 18895–18930.

    Article  CAS  Google Scholar 

  35. Zhang, J.; Zheng, Y.; Lee, J.; Hua, J.; Li, S.; Panchamukhi, A.; Yue, J.; Gou, X.; Xia, Z.; Zhu, L.; Wu, X. A pulsatile release platform based on photo-induced imine-crosslinking hydrogel promotes scarless wound healing. Nat. Commun. 2021, 12, 1670.

    Article  Google Scholar 

  36. Xu, X.; Xia, X.; Zhang, K.; Rai, A.; Li, Z.; Zhao, P.; Wei, K.; Zou, L.; Yang, B.; Wong, W. K.; Chiu, P. W. Y.; Bian, L. Bioadhesive hydrogels demonstrating pH-independent and ultrafast gelation promote gastric ulcer healing in pigs. Sci. Trans. Med. 2020, 12, eaba8014.

    Article  CAS  Google Scholar 

  37. Ahmadian, Z.; Correia, A.; Hasany, M.; Figueiredo, P.; Dobakhti, F.; Eskandari, M. R.; Hosseini, S. H.; Abiri, R.; Khorshid, S.; Hirvonen, J.; Santos, H. A.; Shahbazi, M. A. A hydrogen-bonded extracellular matrix-mimicking bactericidal hydrogel with radical scavenging and hemostatic function for pH-responsive wound healing acceleration. Adv. Healthc. Mater. 2020, 10, 2001122.

    Article  Google Scholar 

  38. Arno, M. C. Engineering the mammalian cell surface with synthetic polymers: strategies and applications. Macromol. Rapid Commun. 2020, 41, 2000302.

    Article  CAS  Google Scholar 

  39. Xu, C.; Yu, B.; Qi, Y.; Zhao, N.; Xu, F. J. Versatile types of cyclodextrin-based nucleic acid delivery systems. Adv. Healthc. Mater. 2020, 10, 2001183.

    Article  Google Scholar 

  40. Cheng, Y.; Zhao, L.; Li, Y.; Xu, T. Design of biocompatible dendrimers for cancer diagnosis and therapy: current status and future perspectives. Chem. Soc. Rev. 2011, 40, 2673.

    Article  CAS  Google Scholar 

  41. Liu, C.; Liu, X.; Liu, C.; Wang, N.; Chen, H.; Yao, W.; Sun, G.; Song, Q.; Qiao, W. A highly efficient, in situ wet-adhesive dextran derivative sponge for rapid hemostasis. Biomaterials 2019, 205, 23–37.

    Article  CAS  Google Scholar 

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Acknowledgments

This work was financially supported by National Key Research and Development Project of China (No. 2021YFB4001101), the National Natural Science Foundation (NSFC) of China (No. 22075176), Natural Science Foundation of Shanghai (No. 22ZR1429200), and NSFC projects (Nos. 51833006, 82071160, 81870806 and 81974152).

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  1. These authors contributed equally to this work.

Authors and Affiliations

  1. School of Chemistry and Chemical Engineering, Frontiers Science Center for Transformative Molecules, Shanghai Key Laboratory of Electrical Insulation and Thermal Aging, Shanghai Jiao Tong University, Shanghai, 200240, China

    Lin Teng & Chang-Ming Dong

  2. Department of Stomatology, Shanghai Jiao Tong University Affiliated Sixth People’s Hospital, Shanghai Jiao Tong University, Shanghai, 200233, China

    Zheng-Wei Shao, Jia-Yu Lu & De-Rong Zou

  3. School of Chemistry and Chemical Engineering, Shanghai Electrochemical Energy Devices Research Center, Shanghai Jiao Tong University, Shanghai, 200240, China

    Yu-Shi He

  4. School of Materials Science and Engineering, State Key Laboratory of Metal Matrix Composites, Shanghai Jiao Tong University, Shanghai, 200240, China

    Chuan-Liang Feng

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  1. Lin Teng
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Correspondence to Jia-Yu Lu or Chang-Ming Dong.

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A Glycosylated and Catechol-crosslinked ε-Polylysine Hydrogel: Simple Preparation and Excellent Wound Hemostasis and Healing Properties

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Teng, L., Shao, ZW., He, YS. et al. A Glycosylated and Catechol-crosslinked ε-Polylysine Hydrogel: Simple Preparation and Excellent Wound Hemostasis and Healing Properties. Chin J Polym Sci 40, 1110–1119 (2022). https://doi.org/10.1007/s10118-022-2741-1

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