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Hierarchical Self-Assembly of Injectable Alginate Supramolecular Nanofibril Hydrogels for Hemostasis In Vivo

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Abstract

Biomass-based supramolecular hydrogels are widely used in the biomedical field due to their favorable biocompatibility and outstanding mechanical properties. However, the preparation of injectable polysaccharide-based hydrogels has proven to be a significant challenge. Here we have employed a simple poor-solvent strategy to prepare alginate supramolecular hydrogels via a hierarchical self-assembly process, including micellization, micelles alignment to form nanofilament, and nanofibrils formation. The alginate supramolecular fibrillar hydrogels exhibit excellent mechanical properties and shear recoverability, meeting the requirements of injectable hydrogels. Furthermore, the presence of alginate and its fibrillar structures imparts superb hemostasis properties and the inherent biocompatibility to these hydrogels. Therefore, this simple and intriguing approach has the potential to develop polysaccharide-based hydrogels for hemostasis in wound within the biomedical fields.

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The data that support the findings of this study are available from the corresponding authors upon request.

References

  1. Levin A, Mason TO, Adler-Abramovich L, Buell AK, Meisl G, Galvagnion C, Bram Y, Stratford SA, Dobson CM, Knowles TP, Gazit E. Ostwald’s rule of stages governs structural transitions and morphology of dipeptide supramolecular polymers. Nat Commun. 2014;5:5219.

    Article  CAS  PubMed  Google Scholar 

  2. Fichman G, Guterman T, Damron J, Adler-Abramovich L, Schmidt J, Kesselman E, Shimon LJW, Ramamoorthy A, Talmon Y, Gazit E. Spontaneous structural transition and crystal formation in minimal supramolecular polymer model. Sci Adv. 2016;2: e1500827.

    Article  PubMed  PubMed Central  Google Scholar 

  3. Lehn J-M. Perspectives in supramolecular chemistry-from molecular recognition towards molecular information processing and self-organization. Angew Chem Int Ed. 1990;29:1304.

    Article  Google Scholar 

  4. Burnworth M, Tang L, Kumpfer JR, Duncan AJ, Beyer FL, Fiore GL, Rowan SJ, Weder C. Optically healable supramolecular polymers. Nature. 2011;472:334.

    Article  CAS  PubMed  Google Scholar 

  5. Hou J, Liu M, Zhang H, Song Y, Jiang X, Yu A, Jiang L, Su B. Healable green hydrogen bonded networks for circuit repair, wearable sensor and flexible electronic devices. J Mater Chem A. 2017;5:13138.

    Article  CAS  Google Scholar 

  6. Lokhande G, Carrow JK, Thakur T, Xavier JR, Parani M, Bayless KJ, Gaharwar AK. Nanoengineered injectable hydrogels for wound healing application. Acta Biomater. 2018;70:35.

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  7. Meng Y, Zou S, Jiang M, Xu X, Tang BZ, Zhang L. Dendritic nanotubes self-assembled from stiff polysaccharides as drug and probe carriers. J Mater Chem B. 2017;5:2616.

    Article  CAS  PubMed  Google Scholar 

  8. Sun Y, Zhang X, Wu T, Zhang Z, Yang R, Liu W. YAP-suppressive nanodrug crosslinked self-immunoregulatory polysaccharide injectable hydrogel for attenuating cardiac fibrosis to treat myocardial infarction. Adv Funct Mater. 2023;33:2214468.

    Article  CAS  Google Scholar 

  9. Cha GD, Kim M, Park OK, Sunwoo SH, Kang T, Lee WH, Nam S, Hyeon T, Choi SH, Kim DH. Minimally-invasive and in-vivo hydrogel patterning method for in situ fabrication of implantable hydrogel devices. Small Methods. 2023;7:2300032.

    Article  CAS  Google Scholar 

  10. Tan W, Long T, Wan Y, Li B, Xu Z, Zhao L, Mu C, Ge L, Li D. Dual-drug loaded polysaccharide-based self-healing hydrogels with multifunctionality for promoting diabetic wound healing. Carbohyd Polym. 2023;312: 120824.

    Article  CAS  Google Scholar 

  11. Yuk H, Lu B, Zhao X. Hydrogel bioelectronics. Chem Soc Rev. 2019;48:1642.

    Article  CAS  PubMed  Google Scholar 

  12. Sunwoo SH, Han SI, Joo H, Cha GD, Kim D, Choi SH, Hyeon T, Kim DH. Advances in soft bioelectronics for brain research and clinical neuroengineering. Matter. 2020;3:1923.

    Article  Google Scholar 

  13. Liu S, Rao Y, Jang H, Tan P, Lu N. Strategies for body-conformable electronics. Matter. 2022;5:1104.

    Article  CAS  Google Scholar 

  14. Duan J, Liang X, Cao Y, Wang S, Zhang L. High strength chitosan hydrogels with biocompatibility via new avenue based on constructing nanofibrous architecture. Macromolecules. 2015;48:2706.

    Article  CAS  Google Scholar 

  15. Jones CD, Kennedy SR, Walker M, Yufit DS, Steed JW. Scrolling of supramolecular lamellae in the hierarchical self-assembly of fibrous gels. Chem. 2017;3:603.

    Article  CAS  Google Scholar 

  16. Zhang S. Fabrication of novel biomaterials through molecular self-assembly. Nat Biotechnol. 2003;21:1171.

    Article  CAS  PubMed  Google Scholar 

  17. Aida T, Meijer EW, Stupp SI. Functional supramolecular polymers. Science. 2012;335:813.

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  18. Adler-Abramovich L, Gazit E. The physical properties of supramolecular peptide assemblies: from building block association to technological applications. Chem Soc Rev. 2014;43:6881.

    Article  CAS  PubMed  Google Scholar 

  19. Ikezoe Y, Washino G, Uemura T, Kitagawa S, Matsui H. Autonomous motors of a metal–organic framework powered by reorganization of self-assembled peptides at interfaces. Nat Mater. 2012;11:1081.

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  20. Hauser CAE, Maurer-Stroh S, Martins IC. Amyloid-based nanosensors and nanodevices. Chem Soc Rev. 2014;43:5326.

    Article  CAS  PubMed  Google Scholar 

  21. Liu Y, Ling S, Wang S, Chen X, Shao Z. Thixotropic silk nanofibril-based hydrogel with extracellular matrix-like structure. Biomater Sci. 2014;2:1338.

    Article  CAS  PubMed  Google Scholar 

  22. Chen Z, Liu X, Ding J, Tian Y, Zhang Y, Wei D, Sun J, Luo F, Zhou L, Fan H. Tissue-like electrophysiological electrode interface construction by multiple crosslinked polysaccharide-based hydrogel. Carbohyd Polym. 2022;296: 119923.

    Article  CAS  Google Scholar 

  23. Wei P, Yu X, Fang Y, Wang L, Zhang H, Zhu C, Cai J. Strong and tough cellulose hydrogels via solution annealing and dual cross-linking. Small. 2023;19:2301204.

    Article  CAS  Google Scholar 

  24. Tong C, Jiang S, Ye D, Li K, Liu J, Zeng X, Wu C, Pang J. Enhanced mechanical property and freeze-thaw stability of alkali-induced heat-set konjac glucomannan hydrogel through anchoring interface effects of carboxylated cellulose nanocrystals. Food Hydrocolloid. 2023;142: 108812.

    Article  CAS  Google Scholar 

  25. Yanaki T, Norisuye T, Fujita H. Triple helix of Schizophyllum commune polysaccharide in dilute solution. 3. Hydrodynamic properties in water. Macromolecules. 1980;13:1462.

    Article  CAS  Google Scholar 

  26. Xu S, Lin Y, Huang J, Li Z, Xu X, Zhang L. Construction of high strength hollow fibers by self-assembly of a stiff polysaccharide with short branches in water. J Mater Chem A. 2013;1:4198.

    Article  CAS  Google Scholar 

  27. Fang Y, Duan B, Lu A, Liu M, Liu H, Xu X, Zhang L. Intermolecular interaction and the extended wormlike chain conformation of chitin in NaOH/urea aqueous solution. Biomacromol. 2015;16:1410.

    Article  CAS  Google Scholar 

  28. Zhang X, Sheng N, Wang L, Tan Y, Liu C, Xia Y, Nie Z, Sui K. Supramolecular nanofibrillar hydrogels as highly stretchable, elastic and sensitive ionic sensors. Mater Horiz. 2019;6:326.

    Article  CAS  Google Scholar 

  29. Zhao C, Zhang C, Kang H, Xia Y, Sui K, Liu R. Gelation of Na-alginate aqueous solution: a study of sodium ion dynamics via NMR relaxometry. Carbohyd Polym. 2017;169:206.

    Article  CAS  Google Scholar 

  30. Dou X, Zhou Q, Chen X, Tan Y, He X, Lu P, Sui K, Tang BZ, Zhang Y, Yuan WZ. Clustering-triggered emission and persistent room temperature phosphorescence of sodium alginate. Biomacromolecules. 2018;19:2014.

    Article  CAS  PubMed  Google Scholar 

  31. Cleland RL. Viscometry and sedimentation equilibrium of partially hydrolyzed hyaluronate: comparison with theoretical models of wormlike chains. Biopolymers. 1984;23:647.

    Article  CAS  Google Scholar 

  32. Mourey T, Le K, Bryan T, Zheng S, Bennett G. Determining persistence length by size-exclusion chromatography. Polymer. 2005;46:9033.

    Article  CAS  Google Scholar 

  33. Vold IMN, Kristiansen KA, Christensen BE. A study of the chain stiffness and extension of alginates, in vitro epimerized alginates, and periodate-oxidized alginates using size-exclusion chromatography combined with light scattering and viscosity detectors. Biomacromol. 2006;7:2136.

    Article  Google Scholar 

  34. McIntire TM, Brant DA. Imaging of carrageenan macrocycles and amylose using noncontact atomic force microscopy. Int J Biol Macromol. 1999;26:303.

    Article  CAS  PubMed  Google Scholar 

  35. Schefer L, Adamcik J, Mezzenga R. Unravelling secondary structure changes on individual anionic polysaccharide chains by atomic force microscopy. Angew Chem Int Ed. 2014;53:5376.

    Article  CAS  Google Scholar 

  36. Asadi-Korayem M, Akbari-Taemeh M, Mohammadian-Sabet F, Shayesteh A, Daemi H. How does counter-cation substitution influence inter- and intramolecular hydrogen bonding and electrospinnability of alginates. Int J Biol Macromol. 2021;171:234.

    Article  CAS  PubMed  Google Scholar 

  37. Xu S, Xu X, Zhang L. Effect of heating on chain conformation of branched β-glucan in water. J Phys Chem B. 2013;117:8370.

    Article  CAS  PubMed  Google Scholar 

  38. Schefer L, Adamcik J, Diener M, Mezzenga R. Supramolecular chiral self-assembly and supercoiling behavior of carrageenans at varying salt conditions. Nanoscale. 2015;7:16182.

    Article  CAS  PubMed  Google Scholar 

  39. Kirwan LJ, Papastavrou G, Borkovec M, Behrens SH. Imaging the coil-to-globule conformational transition of a weak polyelectrolyte by tuning the polyelectrolyte charge density. Nano Lett. 2004;4:149.

    Article  CAS  Google Scholar 

  40. Wang J, Liu K, Xing R, Yan X. Peptide self-assembly: thermodynamics and kinetics. Chem Soc Rev. 2016;45:5589.

    Article  CAS  PubMed  Google Scholar 

  41. Liu Y, Zhang Y, Wang Z, Wang J, Wei K, Chen G, Jiang M. Building nanowires from micelles: hierarchical self-assembly of alternating amphiphilic glycopolypeptide brushes with pendants of high-mannose glycodendron and oligophenylalanine. J Am Chem Soc. 2016;138:12387.

    Article  CAS  PubMed  Google Scholar 

  42. Lampel A, McPhee SA, Park HA, Scott GG, Humagain S, Hekstra DR, Yoo B, Frederix PWJM, Li TD, Abzalimov RR, Greenbaum SG, Tuttle T, Hu C, Bettinger CJ, Ulijn RV. Polymeric peptide pigments with sequence-encoded properties. Science. 2017;356:1064.

    Article  CAS  PubMed  Google Scholar 

  43. Wang J, Chao J, Liu H, Su S, Wang L, Huang W, Willner I, Fan C. Clamped hybridization chain reactions for the self-assembly of patterned DNA hydrogels. Angew Chem Int Ed. 2017;56:2171.

    Article  CAS  Google Scholar 

  44. Levin A, Mason TO, Adler-Abramovich L, Buell AK, Meisl G, Galvagnion C, Bram Y, Stratford SA, Dobson CM, Knowles TPJ, Gazit E. Ostwald’s rule of stages governs structural transitions and morphology of dipeptide supramolecular polymers. Nat Commun. 2014;5:5219.

    Article  CAS  PubMed  Google Scholar 

  45. Meiboom S, Gill D. Modified spin-echo method for measuring nuclear relaxation times. Rev Sci Instrum. 2004;29:688.

    Article  Google Scholar 

  46. Seale R, Morris ER, Rees DA. Interactions of alginates with univalent cations. Carbohyd Res. 1982;110:101.

    Article  CAS  Google Scholar 

  47. Bakota EL, Wang Y, Danesh FR, Hartgerink JD. Injectable multidomain peptide nanofiber hydrogel as a delivery agent for stem cell secretome. Biomacromol. 2011;12:1651.

    Article  CAS  Google Scholar 

  48. Dowling MB, Kumar R, Keibler MA, Hess JR, Bochicchio GV, Raghavan SR. A self-assembling hydrophobically modified chitosan capable of reversible hemostatic action. Biomaterials. 2011;32:3351.

    Article  CAS  PubMed  Google Scholar 

  49. Li J, Celiz AD, Yang J, Yang Q, Wamala I, Whyte W, Seo BR, Vasilyev NV, Vlassak JJ, Suo Z, Mooney DJ. Tough adhesives for diverse wet surfaces. Science. 2017;357:378.

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  50. Qiao H, Qi P, Zhang X, Wang L, Tan Y, Luan Z, Xia Y, Li Y, Sui K. Multiple weak h-bonds lead to highly sensitive, stretchable, self-adhesive, and self-healing ionic sensors. ACS Appl Mater Interfaces. 2019;11:7755.

    Article  CAS  PubMed  Google Scholar 

  51. Lih E, Lee JS, Park KM, Park KD. Rapidly curable chitosan–PEG hydrogels as tissue adhesives for hemostasis and wound healing. Acta Biomater. 2012;8:3261.

    Article  CAS  PubMed  Google Scholar 

  52. Ryu JH, Lee Y, Kong WH, Kim TG, Park TG, Lee H. Catechol-functionalized chitosan/pluronic hydrogels for tissue adhesives and hemostatic materials. Biomacromol. 2011;12:2653.

    Article  CAS  Google Scholar 

  53. Shin M, Park SG, Oh BC, Kim K, Jo S, Lee MS, Oh SS, Hong SH, Shin EC, Kim KS, Kang SW, Lee H. Complete prevention of blood loss with self-sealing haemostatic needles. Nat Mater. 2017;16:147.

    Article  CAS  PubMed  Google Scholar 

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Acknowledgements

This research was supported by State Key Laboratory of Bio-Fibers and Eco-Textiles, Qingdao University (ZDKT202006)

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Authors and Affiliations

  1. State Key Laboratory of Bio-Fibers and Eco-Textiles, College of Materials Science and Engineering, Shandong Collaborative Innovation Center of Marine Biobased Fibers and Ecological Textiles, Qingdao University, Qingdao, 266071, People’s Republic of China

    Linan Wang, Wenwen Hou, Qingxu Zhang, Haiyan Qiao, Min Lin, Zhaocun Shen & Kunyan Sui

  2. Henan Joint International Research Laboratory of Living Polymerizations and Functional Nanomaterials, Henan Key Laboratory of Advanced Nylon Materials and Application, School of Materials Science and Engineering, Zhengzhou University, Zhengzhou, 450001, China

    Linan Wang & Xinchang Pang

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  1. Linan Wang
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Correspondence to Kunyan Sui.

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Wang, L., Hou, W., Zhang, Q. et al. Hierarchical Self-Assembly of Injectable Alginate Supramolecular Nanofibril Hydrogels for Hemostasis In Vivo. Adv. Fiber Mater. 6, 489–500 (2024). https://doi.org/10.1007/s42765-023-00355-8

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