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Biocompatible in situ-forming glycopolypeptide hydrogels

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Abstract

A lack of biological activity hinders the application of synthetic hydrogels in tissue engineering and regenerative medicine. However, the use of glycopolypeptides in hydrogel synthesis may provide the materials with the desired biological activities. Herein, we prepared three in situ-forming hydrogels from various phenol-functionalized glycopolypeptides. The gelation time, mechanical properties, degradation properties, and biocompatibility of the hydrogels were assessed. Gelation time ranged from 11 to 380 s, depending on the concentration of horseradish peroxidase. The galactose-modified polypeptide hydrogel showed the highest storage modulus with an obvious stress relaxation phenomenon. The prepared hydrogels exhibited good degradation properties and compatibility to cells and tissues. Furthermore, the rate of immune cell accumulation around the mannose-modified polypeptide hydrogel was the fastest among the hydrogels.

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References

  1. Pina S, Oliveira J M, Reis R L. Natural-based nanocomposites for bone tissue engineering and regenerative medicine: A review. Adv Mater, 2015, 27: 1143–1169

    Article  Google Scholar 

  2. Griffith L G, Naughton G. Tissue engineering-current challenges and expanding opportunities. Science, 2002, 295: 1009–1014

    Article  Google Scholar 

  3. Langer R, Vacanti J P. Tissue engineering. Science, 1993, 260: 920–926

    Article  Google Scholar 

  4. Li Y, Rodrigues J, Tomas H. Injectable and biodegradable hydrogels: Gelation, biodegradation and biomedical applications. Chem Soc Rev, 2012, 41: 2193–2221

    Article  Google Scholar 

  5. Annabi N, Tamayol A, Uquillas J A, et al. 25th anniversary article: Rational design and applications of hydrogels in regenerative medicine. Adv Mater, 2014, 26: 85–124

    Article  Google Scholar 

  6. Hussey G S, Dziki J L, Badylak S F. Extracellular matrix-based materials for regenerative medicine. Nat Rev Mater, 2018, 3: 159–173

    Article  Google Scholar 

  7. Pérez R A, Won J E, Knowles J C, et al. Naturally and synthetic smart composite biomaterials for tissue regeneration. Adv Drug Deliver Rev, 2013, 65: 471–496

    Article  Google Scholar 

  8. Place E S, Evans N D, Stevens M M. Complexity in biomaterials for tissue engineering. Nat Mater, 2009, 8: 457–470

    Article  Google Scholar 

  9. Lutolf M P, Hubbell J A. Synthetic biomaterials as instructive extracellular microenvironments for morphogenesis in tissue engineering. Nat Biotech, 2005, 23: 47–55

    Article  Google Scholar 

  10. Dvir T, Timko B P, Kohane D S, et al. Nanotechnological strategies for engineering complex tissues. Nat Nanotech, 2011, 6: 13–22

    Article  Google Scholar 

  11. Krannig K S, Schlaad H. Emerging bioinspired polymers: Glycopolypeptides. Soft Matter, 2014, 10: 4228–4235

    Article  Google Scholar 

  12. Tsang K Y, Cheung M C H, Chan D, et al. The developmental roles of the extracellular matrix: Beyond structure to regulation. Cell Tissue Res, 2010, 339: 93–110

    Article  Google Scholar 

  13. Rozario T, DeSimone D W. The extracellular matrix in development and morphogenesis: A dynamic view. Dev Biol, 2010, 341: 126–140

    Article  Google Scholar 

  14. Godula K, Bertozzi C R. Synthesis of glycopolymers for microarray applications via ligation of reducing sugars to a poly(acryloyl hydrazide) scaffold. J Am Chem Soc, 2010, 132: 9963–9965

    Article  Google Scholar 

  15. Kramer J R, Deming T J. Glycopolypeptides via living polymerization of glycosylated-l-lysine N-carboxyanhydrides. J Am Chem Soc, 2010, 132: 15068–15071

    Article  Google Scholar 

  16. Mecham R P. The Extracellular Matrix: An Overview. Berlin: Springer, 2011

    Book  Google Scholar 

  17. Rawat M, Gama C I, Matson J B, et al. Neuroactive chondroitin sulfate glycomimetics. J Am Chem Soc, 2008, 130: 2959–2961

    Article  Google Scholar 

  18. Oh Y I, Sheng G J, Chang S K, et al. Tailored glycopolymers as anticoagulant heparin mimetics. Angew Chem Int Ed, 2013, 52: 11796–11799

    Article  Google Scholar 

  19. Kramer J R, Deming T J. Recent advances in glycopolypeptide synthesis. Polym Chem, 2014, 5: 671–682

    Article  Google Scholar 

  20. Herzner H, Reipen T, Schultz M, et al. Synthesis of glycopeptides containing carbohydrate and peptide recognition motifs. Chem Rev, 2000, 100: 4495–4538

    Article  Google Scholar 

  21. Wang Y, Kiick K L. Monodisperse protein-based glycopolymers via a combined biosynthetic and chemical approach. J Am Chem Soc, 2005, 127: 16392–16393

    Article  Google Scholar 

  22. Miura Y. Design and synthesis of well-defined glycopolymers for the control of biological functionalities. Polym J, 2012, 44: 679–689

    Article  Google Scholar 

  23. Geng J, Mantovani G, Tao L, et al. Site-directed conjugation of “clicked” glycopolymers to form glycoprotein mimics: Binding to mammalian lectin and induction of immunological function. J Am Chem Soc, 2007, 129: 15156–15163

    Article  Google Scholar 

  24. Miura Y, Hoshino Y, Seto H. Glycopolymer nanobiotechnology. Chem Rev, 2016, 116: 1673–1692

    Article  Google Scholar 

  25. Ren K, He C, Xiao C, et al. Injectable glycopolypeptide hydrogels as biomimetic scaffolds for cartilage tissue engineering. Biomaterials, 2015, 51: 238–249

    Article  Google Scholar 

  26. Xiao C, Zhao C, He P, et al. Facile synthesis of glycopolypeptides by combination of ring-opening polymerization of an Alkyne-Substituted N-carboxyanhydride and click “glycosylation”. Macromol Rapid Commun, 2010, 31: 991–997

    Article  Google Scholar 

  27. Huang Y, Zeng Y, Yang J, et al. Facile functionalization of polypeptides by thiol-yne photochemistry for biomimetic materials synthesis. Chem Commun, 2011, 47: 7509–7511

    Article  Google Scholar 

  28. Engler A C, Lee H, Hammond P T. Highly efficient “grafting onto” a polypeptide backbone using click chemistry. Angew Chem Int Ed, 2009, 48: 9334–9338

    Article  Google Scholar 

  29. Lu H, Cheng J. Hexamethyldisilazane-mediated controlled polymerization of α-amino acid N-carboxyanhydrides. J Am Chem Soc, 2007, 129: 14114–14115

    Article  Google Scholar 

  30. Levene P. The pentacetate of α-mannose. J Biol Chem., 1924, 59: 141–144

    Google Scholar 

  31. Ladmiral V, Mantovani G, Clarkson G J, et al. Synthesis of neoglycopolymers by a combination of “click chemistry” and living radical polymerization. J Am Chem Soc, 2006, 128: 4823–4830

    Article  Google Scholar 

  32. Bae J W, Choi J H, Lee Y, et al. Horseradish peroxidase-catalysed in situ-forming hydrogels for tissue-engineering applications. J Tissue Eng Regen Med, 2015, 9: 1225–1232

    Article  Google Scholar 

  33. Yu L, Ding J. Injectable hydrogels as unique biomedical materials. Chem Soc Rev, 2008, 37: 1473–1481

    Article  Google Scholar 

  34. Wang D, Yang X, Liu Q, et al. 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  Google Scholar 

  35. Jin R, Hiemstra C, Zhong Z, et al. Enzyme-mediated fast in situ formation of hydrogels from dextran-tyramine conjugates. Biomaterials, 2007, 28: 2791–2800

    Article  Google Scholar 

  36. Veitch N C. Horseradish peroxidase: A modern view of a classic enzyme. Phytochemistry, 2004, 65: 249–259

    Article  Google Scholar 

  37. Park K M, Shin Y M, Joung Y K, et al. In situ forming hydrogels based on tyramine conjugated 4-arm-PPO-PEO via enzymatic oxidative reaction. Biomacromolecules, 2010, 11: 706–712

    Article  Google Scholar 

  38. Huebsch N, Lippens E, Lee K, et al. Matrix elasticity of void-forming hydrogels controls transplanted-stem-cell-mediated bone formation. Nat Mater, 2015, 14: 1269–1277

    Article  Google Scholar 

  39. Lee H P, Gu L, Mooney D J, et al. Mechanical confinement regulates cartilage matrix formation by chondrocytes. Nat Mater, 2017, 16: 1243–1251

    Article  Google Scholar 

  40. Gilbert P M, Havenstrite K L, Magnusson K E G, et al. Substrate elasticity regulates skeletal muscle stem cell self-renewal in culture. Science, 2010, 329: 1078–1081

    Article  Google Scholar 

  41. Dashnau J L, Sharp K A, Vanderkooi J M. Carbohydrate intramolecular hydrogen bonding cooperativity and its effect on water structure. J Phys Chem B, 2005, 109: 24152–24159

    Article  Google Scholar 

  42. Murphy C M, Haugh M G, O’Brien F J. The effect of mean pore size on cell attachment, proliferation and migration in collagen-glycosaminoglycan scaffolds for bone tissue engineering. Biomaterials, 2010, 31: 461–466

    Article  Google Scholar 

  43. O’Brien F J, Harley B A, Yannas I V, et al. The effect of pore size on cell adhesion in collagen-GAG scaffolds. Biomaterials, 2005, 26: 433–441

    Article  Google Scholar 

  44. Wu D Q, Sun Y X, Xu X D, et al. Biodegradable and pH-sensitive hydrogels for cell encapsulation and controlled drug release. Biomacromolecules, 2008, 9: 1155–1162

    Article  Google Scholar 

  45. Anderson J M, Rodriguez A, Chang D T. Foreign body reaction to biomaterials. Seminars Immunol, 2008, 20: 86–100

    Article  Google Scholar 

  46. Chernyak A Y, Sharma G V M, Kononov L O, et al. 2-Azidoethyl glycosides: Glycosides potentially useful for the preparation of neoglycoconjugates. Carbohydrate Res, 1992, 223: 303–309

    Article  Google Scholar 

  47. Oswald L, Trinh T T, Chan-Seng D, et al. Debromination of ATRP-made wang soluble polymer supports. Polymer, 2015, 72: 341–347

    Article  Google Scholar 

  48. Chen C, Wang Z, Li Z. Thermoresponsive polypeptides from pegylated poly-l-glutamates. Biomacromolecules, 2011, 12: 2859–2863

    Article  Google Scholar 

  49. Poché D S, Moore M J, Bowles J L. An unconventional method for purifying the N-carboxyanhydride derivatives of γ-alkyl-L-glutamates. Synth Commun, 1999, 29: 843–854

    Article  Google Scholar 

  50. Daly W H, Poché D. The preparation of N-carboxyanhydrides of α-amino acids using bis(trichloromethyl)carbonate. Tetrahedron Lett, 1988, 29: 5859–5862

    Article  Google Scholar 

  51. Jeong B, Bae Y H, Kim S W. Thermoreversible gelation of PEG-PLGA-PEG triblock copolymer aqueous solutions. Macromolecules, 1999, 32: 7064–7069

    Article  Google Scholar 

  52. Park H, Guo X, Temenoff J S, et al. Effect of swelling ratio of injectable hydrogel composites on chondrogenic differentiation of encapsulated rabbit marrow mesenchymal stem cells in vitro. Biomacromolecules, 2009, 10: 541–546

    Article  Google Scholar 

  53. Liu X, Jin X, Ma P X. Nanofibrous hollow microspheres self-assembled from star-shaped polymers as injectable cell carriers for knee repair. Nat Mater, 2011, 10: 398–406

    Article  Google Scholar 

  54. Yoon H I, Yhee J Y, Na J H, et al. Bioorthogonal copper free click chemistry for labeling and tracking of chondrocytes in vivo. Bioconjugate Chem, 2016, 27: 927–936

    Article  Google Scholar 

  55. Monks A, Scudiero D, Skehan P, et al. Feasibility of a high-flux anticancer drug screen using a diverse panel of cultured human tumor cell lines. J Natl Cancer Inst, 1991, 83: 757–766

    Article  Google Scholar 

  56. Kloxin A M, Tibbitt M W, Anseth K S. Synthesis of photodegradable hydrogels as dynamically tunable cell culture platforms. Nat Protoc, 2010, 5: 1867–1887

    Article  Google Scholar 

  57. Yesilyurt V, Webber M J, Appel E A, et al. Injectable self-healing glucose-responsive hydrogels with pH-regulated mechanical properties. Adv Mater, 2016, 28: 86–91

    Article  Google Scholar 

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Authors and Affiliations

  1. CAS Key Laboratory of Polymer Ecomaterials, Changchun Institute of Applied Chemistry, Chinese Academy of Sciences, Changchun, 130022, China

    Shun Shi, ShuangJiang Yu, Gao Li, ChaoLiang He & XueSi Chen

  2. College of Applied Chemistry and Engineering, University of Science and Technology of China, Hefei, 230026, China

    Shun Shi, Gao Li, ChaoLiang He & XueSi Chen

  3. Jilin Biomedical Polymers Engineering Laboratory, Changchun, 130022, China

    Shun Shi, ShuangJiang Yu, Gao Li, ChaoLiang He & XueSi Chen

Authors
  1. Shun Shi
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  2. ShuangJiang Yu
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  3. Gao Li
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  4. ChaoLiang He
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  5. XueSi Chen
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Corresponding authors

Correspondence to Gao Li or ChaoLiang He.

Additional information

This work was supported by the National Natural Science Foundation of China (Grant Nos. 21574127, 51622307, 51520105004, 51833010 and 51773199), and the Youth Innovation Promotion Association, CAS.

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The supporting information is available online at tech.scichina.com and link.springer.com . The supporting materials are published as submitted, without typesetting or editing. The responsibility for scientific accuracy and content remains entirely with the authors.

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Shi, S., Yu, S., Li, G. et al. Biocompatible in situ-forming glycopolypeptide hydrogels. Sci. China Technol. Sci. 63, 992–1004 (2020). https://doi.org/10.1007/s11431-019-1466-1

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  • DOI: https://doi.org/10.1007/s11431-019-1466-1

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