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Catechol-modified hyaluronic acid: in situ-forming hydrogels by auto-oxidation of catechol or photo-oxidation using visible light

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Abstract

Mussel-inspired polymers have emerged as attractive candidates for the synthesis of injectable hydrogels with tissue-adhesive properties. In these systems, polymer crosslinking occurs via the oxidative coupling of catechol groups grafted on the polymer backbone, performed in the presence of an enzyme or a chemical oxidant. Here, we show that catechol-modified hyaluronic acid (HA-CA) can self-crosslink in physiological conditions without any requirement of oxidizing reagents. A careful rheological analysis of gelation of HA-CA solutions indicated that both the degree of substitution and the molar mass of HA-CA are key parameters controlling the gelation kinetics. Interestingly, the gelation time could be dramatically lowered by photo-oxidation of catechol using visible light in the presence of eosin Y as a photosensitizer. This strategy can be advantageously used to manage viscosity and gelation kinetics during injection, which paves the way for various biomedical applications of HA-CA including wound closure and healing as well as drug delivery.

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References

  1. Hoffman AS (2013) Stimuli-responsive polymers: biomedical applications and challenges for clinical translation. Adv Drug Deliv Rev 65:10–16

    Article  CAS  Google Scholar 

  2. Kirschner CM, Anseth KS (2013) Hydrogels in healthcare: from static to dynamic material microenvironments. Acta Mater 61:931–944

    Article  CAS  Google Scholar 

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

    Article  CAS  Google Scholar 

  4. Peppas NA, Hilt JZ, Khademhosseini A, Langer R (2006) Hydrogels in biology and medicine: from molecular principles to bionanotechnology. Adv Mater 18:1345–1360

    Article  CAS  Google Scholar 

  5. Bae KH, Wang L-S, Kurisawa M (2013) Injectable biodegradable hydrogels: progress and challenges. J Mater Chem B Mater Biol Med 1:5371–5388

    Article  CAS  Google Scholar 

  6. Hunt JA, Chen R, van Veen T, Bryan N (2014) Hydrogels for tissue engineering and regenerative medicine. J Mater Chem B Mater Biol Med 2:5319–5338

    Article  CAS  Google Scholar 

  7. Huynh CT, Nguyen MK, Lee DS (2011) Injectable block copolymer hydrogels: achievements and future challenges for biomedical applications. Macromolecules 44:6629–6636

    Article  CAS  Google Scholar 

  8. Joo MK, Park MH, Choi BG, Jeong B (2009) Reverse thermogelling biodegradable polymer aqueous solutions. J Mater Chem 19:5891–5905

    Article  CAS  Google Scholar 

  9. Kim DY, Kwon DY, Kwon JS, Kim JH, Min BH, Kim MS (2015) Stimuli-responsive injectable in situ-forming hydrogels for regenerative medicines. Polym Rev 55:407–452

    Article  CAS  Google Scholar 

  10. Teixeira LSM, Feijen J, van Blitterswijk CA, Dijkstra PJ, Karperien M (2012) Enzyme-catalyzed crosslinkable hydrogels: emerging strategies for tissue engineering. Biomaterials 33:1281–1290

    Article  Google Scholar 

  11. Nguyen MK, Lee DS (2010) Injectable biodegradable hydrogels. Macromol Biosci 10:563–579

    Article  CAS  Google Scholar 

  12. Patenaude M, Smeets NMB, Hoare T (2014) Designing injectable, covalently cross-linked hydrogels for biomedical applications. Macromol Rapid Commun 35:598–617

    Article  CAS  Google Scholar 

  13. Fu S, Ni P, Wang B, Chu B, Zheng L, Luo F, Luo J, Qian Z (2012) Injectable and thermo-sensitive PEG-PCL-PEG copolymer/collagen/n-HA hydrogel composite for guided bone regeneration. Biomaterials 33:4801–4809

    Article  CAS  Google Scholar 

  14. Hou Q, De Bank PA, Shakesheff KM (2004) Injectable scaffolds for tissue regeneration. J Mater Chem 14:1915–1923

    Article  CAS  Google Scholar 

  15. Yang J-A, Yeom J, Hwang BW, Hoffman AS, Hahn SK (2014) In situ-forming injectable hydrogels for regenerative medicine. Prog Polym Sci 39:1973–1986

    Article  CAS  Google Scholar 

  16. Lee Y, Chung HJ, Yeo S, Ahn C-H, Lee H, Messersmith PB, Park TG (2010) Thermo-sensitive, injectable, and tissue adhesive sol-gel transition hyaluronic acid/pluronic composite hydrogels prepared from bio-inspired catechol-thiol reaction. Soft Matter 6:977–983

    Article  CAS  Google Scholar 

  17. Lee SH, Lee Y, Lee S-W, Ji H-Y, Lee J-H, Lee DS, Park TG (2011) Enzyme-mediated cross-linking of pluronic copolymer micelles for injectable and in situ forming hydrogels. Acta Biomater 7:1468–1476

    Article  CAS  Google Scholar 

  18. Deming TJ (1999) Mussel byssus and biomolecular materials. Curr Opin Chem Biol 3(1):100–105

    Article  CAS  Google Scholar 

  19. Lee BP, Messersmith PB, Israelachvili JN, Waite JH (2011) Mussel-inspired adhesives and coatings. Annu Rev Mater Res 41:99–132

    Article  CAS  Google Scholar 

  20. Yu M, Hwang J, Deming TJ (1999) Role of L-3,4-dihydroxyphenylalanine in mussel adhesive proteins. J Am Chem Soc 121:5825–5826

    Article  CAS  Google Scholar 

  21. Lee BP, Dalsin JL, Messersmith PB (2002) Synthesis and gelation of DOPA-modified poly(ethylene glycol) hydrogels. Biomacromolecules 3:1038–1047

    Article  CAS  Google Scholar 

  22. Shin J, Lee JS, Lee C, Park H-J, Yang K, Jin Y, Ryu JH, Hong KS, Moon S-H, Chung H-M, Yang HS, Um SH, Oh J-W, Kim D-I, Lee H, Cho S-W (2015) Tissue adhesive catechol-modified hyaluronic acid hydrogel for effective, minimally invasive cell therapy. Adv Funct Mater 25:3814–3824

    Article  CAS  Google Scholar 

  23. Kim K, Ryu JH, Lee DY, Lee H (2013) Bio-inspired catechol conjugation converts water-insoluble chitosan into a highly water-soluble, adhesive chitosan derivative for hydrogels and LbL assembly. Biomater Sci 1:783–790

    Article  CAS  Google Scholar 

  24. Lee C, Shin J, Lee JS, Byun E, Ryu JH, Um SH, Kim DI, Lee H, Cho SW (2013) Bioinspired, calcium-free alginate hydrogels with tunable physical and mechanical properties and improved biocompatibility. Biomacromolecules 14:2004–2013

    Article  CAS  Google Scholar 

  25. Hong S, Yang K, Kang B, Lee C, Song IT, Byun E, Park KI, Cho SW, Lee H (2013) Hyaluronic acid catechol: a biopolymer exhibiting a pH-dependent adhesive or cohesive property for human neural stem cell engineering. Adv Funct Mater 23:1774–1780

    Article  CAS  Google Scholar 

  26. Destaing O, Planus E, Bouvard D, Oddou C, Badowski C, Bossy V, Raducanu A, Fourcade B, Albiges-Rizo C, Block MR (2010) β1A integrin is a master regulator of invadosome organization and function. Mol Biol Cell 21:4108–4119

    Article  CAS  Google Scholar 

  27. Chung H, Grubbs RH (2012) Rapidly cross-linkable DOPA containing terpolymer adhesives and PEG-based cross-linkers for biomedical applications. Macromolecules 45:9666–9673

    Article  CAS  Google Scholar 

  28. Faessler R, Pfaff M, Murphy J, Noegel AA, Johansson S, Timpl R, Albrecht R (1995) Lack of β1 integrin gene in embryonic stem cells affects morphology, adhesion, and migrations but not integration into the inner cell mass of blastocysts. J Cell Biol 128:979–988

    Article  CAS  Google Scholar 

  29. Mansukhani A, Bellosta P, Sahni M, Basilico C (2000) Signaling by fibroblast growth factors (FGF) and fibroblast growth factor receptor 2 (FGFR2)–activating mutations blocks mineralization and induces apoptosis in osteoblasts. J Cell Biol 149:1297–1308

    Article  CAS  Google Scholar 

  30. Bouvard D, Aszodi A, Kostka G, Block MR, Albiges-Rizo C, Fassler R (2007) Defective osteoblast function in ICAP-1-deficient mice. Development 134:2615–2625

    Article  CAS  Google Scholar 

  31. Yang J, Stuart MAC, Kamperman M (2014) Jack of all trades: versatile catechol crosslinking mechanisms. Chem Soc Rev 43:8271–8298

    Article  CAS  Google Scholar 

  32. Kalyanaraman B, Felix CC, Sealy RC (1985) Semiquinone anion radicals of catechol (amine)s, catechol estrogens, and their metal ion complexes. Environ Health Perspect 64:185–198

    Article  CAS  Google Scholar 

  33. Burzio LA, Waite JH (2000) Cross-linking in adhesive quinoproteins: studies with model decapeptides. Biochemistry 39:11147–11153

    Article  CAS  Google Scholar 

  34. Loebel C, Broguiere N, Alini M, Zenobi-Wong M, Eglin D (2015) Microfabrication of photo-cross-linked hyaluronan hydrogels by single- and two-photon tyramine oxidation. Biomacromolecules 16:2624–2630

    Article  CAS  Google Scholar 

  35. Bonino CA, Samorezov JE, Jeon O, Alsberg E, Khan SA (2011) Real-time in situ rheology of alginate hydrogel photocrosslinking. Soft Matter 7:11510–11517

    Article  CAS  Google Scholar 

  36. Kavanagh GM, Ross-Murphy SB (1998) Rheological characterization of polymer gels. Prog Polym Sci 23:533–562

    Article  CAS  Google Scholar 

  37. Andersen SO, Jacobsen JP, Bojesen G, Roepstorff P (1992) Phenoloxidase catalyzed coupling of catechols. Identification of novel coupling products. Biochim Biophys Acta 1118:134–138

    Article  CAS  Google Scholar 

  38. Barreto WJ, Ponzoni S, Sassi P (1999) A Raman and UV-vis study of catecholamines oxidized with Mn(III). Spectrochim Acta Part A Mol Biomol Spectrosc 55A:65–72

    CAS  Google Scholar 

  39. Linert W, Herlinger E, Jameson RF, Kienzl E, Jellinger K, Youdim MBH (1996) Dopamine, 6-hydroxydopamine, iron, and dioxygen—their mutual interactions and possible implication in the development of Parkinson’s disease. Biochim Biophys Acta 1316:160–168

    Article  Google Scholar 

  40. Zafar KS, Siegel D, Ross D (2006) A potential role for cyclized quinones derived from dopamine, DOPA, and 3,4-dihydroxyphenylacetic acid in proteasomal inhibition. Mol Pharmacol 70:1079–1086

    Article  CAS  Google Scholar 

  41. Turturro MV, Sokic S, Larson JC, Papavasiliou G (2013) Effective tuning of ligand incorporation and mechanical properties in visible light photopolymerized poly(ethylene glycol) diacrylate hydrogels dictates cell adhesion and proliferation. Biomed Mater 8:025001–025012 (Bristol, United Kingdom)

    Article  Google Scholar 

  42. Kang X, Yu Y, Bao Y, Cai W, Cui S (2015) Real time quantification of the chemical cross-link density of a hydrogel by in situ UV-vis spectroscopy. Polym Chem 6:4252–4257

    Article  CAS  Google Scholar 

  43. Zwicker EF, Grossweiner LI (1963) Transient measurements of photochemical processes in dyes. II. The mechanism of the photosensitized oxidation of aqueous phenol by eosin. J Phys Chem 67:549–555

    Article  CAS  Google Scholar 

  44. Bahney CS, Lujan TJ, Hsu CW, Bottlang M, West JL, Johnstone B (2011) Visible light photoinitiation of mesenchymal stem cell-laden bioresponsive hydrogels. Eur Cells Mater 22:43–55

    Article  CAS  Google Scholar 

  45. Waite JH, Qin X (2001) Polyphosphoprotein from the adhesive pads of Mytilus edulis. Biochemistry 40:2887–2893

    Article  CAS  Google Scholar 

  46. Waite JH, Tanzer ML (1980) The bioadhesive of Mytilus byssus: a protein containing L-dopa. Biochem Biophys Res Commun 96:1554–1561

    Article  CAS  Google Scholar 

  47. Ryu JH, Lee Y, Do MJ, Jo SD, Kim JS, Kim BS, Im GI, Park TG, Lee H (2014) Chitosan-g-hematin: enzyme-mimicking polymeric catalyst for adhesive hydrogels. Acta Biomater 10:224–233

    Article  CAS  Google Scholar 

  48. Zhou J, Defante AP, Lin F, Xu Y, Yu J, Gao Y, Childers E, Dhinojwala A, Becker ML (2015) Adhesion properties of catechol-based biodegradable amino acid-based poly(ester urea) copolymers inspired from mussel proteins. Biomacromolecules 16:266–274

    Article  CAS  Google Scholar 

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Acknowledgements

This work was financially supported by a Grant-in-Aid for JSPS Fellows KAKENHI (Grant No. 265612). We are grateful to Prof. M. R. Block for the cell viability testing of the HA-CA hydrogels. We thank Eric Bayma-Pecit for his technical help in the rheological experiments.

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Authors and Affiliations

  1. Grenoble Alpes University, CERMAV-CNRS, 38000, Grenoble, France

    Takeshi Sato & Rachel Auzély-Velty

  2. Graduate School of Pure and Applied Sciences, University of Tsukuba, Tennodai, Tsukuba, Ibaraki, 305-8577, Japan

    Takeshi Sato & Mitsuhiro Ebara

  3. International Center for Materials Nanoarchitectonics (MANA), National Institute for Materials Science (NIMS), Tsukuba, Ibaraki, 305-0044, Japan

    Takeshi Sato & Mitsuhiro Ebara

  4. College of Science and Technology, Nihon University, 1-8-14 Kanda Surugadai, Chiyoda-Ku, Tokyo, 101-8308, Japan

    Takao Aoyagi

  5. Graduate School of Industrial Science and Technology, Tokyo University of Science, Tokyo, 125-8585, Japan

    Mitsuhiro Ebara

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  1. Takeshi Sato
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Correspondence to Rachel Auzély-Velty.

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Sato, T., Aoyagi, T., Ebara, M. et al. Catechol-modified hyaluronic acid: in situ-forming hydrogels by auto-oxidation of catechol or photo-oxidation using visible light. Polym. Bull. 74, 4069–4085 (2017). https://doi.org/10.1007/s00289-017-1937-y

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  • DOI: https://doi.org/10.1007/s00289-017-1937-y

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