Cellulose

, Volume 25, Issue 1, pp 559–571 | Cite as

Self-healing and injectable polysaccharide hydrogels with tunable mechanical properties

  • Hongchen Liu
  • Chaojing Li
  • Bijia Wang
  • Xiaofeng Sui
  • Lu Wang
  • Xiaolin Yan
  • Hong Xu
  • Linping Zhang
  • Yi Zhong
  • Zhiping Mao
Original Paper
  • 418 Downloads

Abstract

An injectable polysaccharide hydrogel based on cellulose acetoacetate (CAA), hydroxypropyl chitosan (HPCS), and amino-modified cellulose nanocrystals (CNC-NH2) was prepared under physiological conditions. CNC-NH2 acted as both physical and chemical cross-linker. The effects of CNC-NH2 loading on the mechanical properties, internal morphology and gelation time were investigated; the maximum storage modulus was observed for a gel containing 0.80 wt% of CNC-NH2. The structure and properties of the polysaccharide hydrogel were characterized by Fourier-transform infrared spectroscopy, nuclear magnetic resonance spectroscopy, scanning electron microscopy, Raman spectroscopy and rheology testing. The polysaccharide hydrogel exhibited pH- responsive properties and excellent stability under physiological conditions. The hydrogel also exhibited self-healing behavior under acidic conditions via enamine bond exchange. In addition, CCK-8 cytotoxicity study with fibroblast L929 cells demonstrates good biocompatibility of CNCs reinforced hydrogels.

Keywords

Self-healing Injectable polysaccharide hydrogel Cellulose nanocrystals Enamine bond 

Notes

Acknowledgments

This work was financially supported by the National Natural Science Foundation of China (No. 51403035), the Natural Science Foundation of Inner Mongolia (2015MS0209), and the Fundamental Research Funds for the Central Universities (No. 15D110510).

References

  1. Asako Hirai OI, Horii Fumitaka, Tsuji Masaki (2009) Phase separation behavior in aqueous suspensions of bacterial cellulose nanocrystals prepared by sulfuric acid treatment. Langmuir 25:497–502.  https://doi.org/10.1021/la802947m CrossRefGoogle Scholar
  2. Barros SC et al (2015) Thermal–mechanical behaviour of chitosan–cellulose derivative thermoreversible hydrogel films. Cellulose 22:1911–1929.  https://doi.org/10.1007/s10570-015-0603-5 CrossRefGoogle Scholar
  3. Bhatia SK, Arthur SD (2008) Poly(vinyl alcohol) acetoacetate-based tissue adhesives are non-cytotoxic and non-inflammatory. Biotechnol Lett 30:1339–1345.  https://doi.org/10.1007/s10529-008-9709-2 CrossRefGoogle Scholar
  4. Cao L, Cao B, Lu C, Wang G, Yu L, Ding J (2015) An injectable hydrogel formed by in situ cross-linking of glycol chitosan and multi-benzaldehyde functionalized PEG analogues for cartilage tissue engineering. J Mater Chem B 3:1268–1280.  https://doi.org/10.1039/c4tb01705f CrossRefGoogle Scholar
  5. Casuso P, Odriozola I, Perez-San Vicente A, Loinaz I, Cabanero G, Grande HJ, Dupin D (2015) Injectable and self-healing dynamic hydrogels based on metal(I)-thiolate/disulfide exchange as biomaterials with tunable mechanical properties. Biomacromol 16:3552–3561.  https://doi.org/10.1021/acs.biomac.5b00980 CrossRefGoogle Scholar
  6. Chang C, Zhang L (2011) Cellulose-based hydrogels: present status and application prospects. Carbohydr Polym 84:40–53.  https://doi.org/10.1016/j.carbpol.2010.12.023 CrossRefGoogle Scholar
  7. Chang G, Chen Y, Li Y, Li S, Huang F, Shen Y, Xie A (2015) Self-healable hydrogel on tumor cell as drug delivery system for localized and effective therapy. Carbohydr Polym 122:336–342.  https://doi.org/10.1016/j.carbpol.2014.12.077 CrossRefGoogle Scholar
  8. Chau M et al (2016) Composite hydrogels with tunable anisotropic morphologies and mechanical properties. Chem Mater 28:3406–3415.  https://doi.org/10.1021/acs.chemmater.6b00792 CrossRefGoogle Scholar
  9. De France KJ, Chan KJ, Cranston ED, Hoare T (2016) Enhanced mechanical properties in cellulose nanocrystal-poly(oligoethylene glycol methacrylate) injectable nanocomposite hydrogels through control of physical and chemical cross-linking. Biomacromol 17:649–660.  https://doi.org/10.1021/acs.biomac.5b01598 CrossRefGoogle Scholar
  10. De France KJ, Hoare T, Cranston ED (2017) Review of hydrogels and aerogels containing nanocellulose. Chem Mater.  https://doi.org/10.1021/acs.chemmater.7b00531 Google Scholar
  11. Deng G et al (2012) Dynamic hydrogels with an environmental adaptive self-healing ability and dual responsive sol–gel transitions. ACS Macro Lett 1:275–279.  https://doi.org/10.1021/mz200195n CrossRefGoogle Scholar
  12. Dong S, Roman M (2007) Fluorescently labeled cellulose nanocrystals for bioimaging applications. J Am Chem Soc 129:13810–13811CrossRefGoogle Scholar
  13. Dufresne A (2017) Cellulose nanomaterial reinforced polymer nanocomposites. Curr Opin Colloid Interface Sci 29:1–8.  https://doi.org/10.1016/j.cocis.2017.01.004 CrossRefGoogle Scholar
  14. Gao N et al (2016) Injectable shell-crosslinked F127 micelle/hydrogel composites with pH and redox sensitivity for combined release of anticancer drugs. Chem Eng J 287:20–29.  https://doi.org/10.1016/j.cej.2015.11.015 CrossRefGoogle Scholar
  15. Hu Z, Cranston ED, Ng R, Pelton R (2014) Tuning cellulose nanocrystal gelation with polysaccharides and surfactants. Langmuir 30:2684–2692.  https://doi.org/10.1021/la404977t CrossRefGoogle Scholar
  16. Kang H, Liu R, Huang Y (2016) Cellulose-Based Gels. Macromol. Chem Phys 217:1322–1344.  https://doi.org/10.1002/macp.201500493 Google Scholar
  17. Li Y, Rodrigues J, Tomás H (2012) Injectable and biodegradable hydrogels: gelation, biodegradation and biomedical applications. Chem Soc Rev 41:2193–2221.  https://doi.org/10.1039/c1cs15203c CrossRefGoogle Scholar
  18. Li Z et al (2016) Mussel-inspired multifunctional supramolecular hydrogels with self-healing, shape memory and adhesive properties. Polym Chem 7:5343–5346.  https://doi.org/10.1039/c6py01112h CrossRefGoogle Scholar
  19. Lin N, Dufresne A (2013) Supramolecular hydrogels from in situ host-guest inclusion between chemically modified cellulose nanocrystals and cyclodextrin. Biomacromol 14:871–880.  https://doi.org/10.1021/bm301955k CrossRefGoogle Scholar
  20. Lin L-J, Larsson M, Liu D-M (2011) A novel dual-structure, self-healable, polysaccharide based hybrid nanogel for biomedical uses. Soft Matter 7:5816–5825.  https://doi.org/10.1039/c1sm05249g CrossRefGoogle Scholar
  21. Liu Y, Li Y, Yang G, Zheng X, Zhou S (2015) Multi-stimulus-responsive shape-memory polymer nanocomposite network cross-linked by cellulose nanocrystals. ACS Appl Mater Interfaces 7:4118–4126.  https://doi.org/10.1021/am5081056 CrossRefGoogle Scholar
  22. Liu H, Sui X, Xu H, Zhang L, Zhong Y, Mao Z (2016) Self-healing polysaccharide hydrogel based on dynamic covalent enamine bonds. Macromol Mater Eng 301:725–732.  https://doi.org/10.1002/mame.201600042 CrossRefGoogle Scholar
  23. Lu S et al (2015) Injectable and self-healing carbohydrate-based hydrogel for cell encapsulation. ACS Appl Mater Interfaces 7:13029–13037.  https://doi.org/10.1021/acsami.5b03143 CrossRefGoogle Scholar
  24. McKee JR, Appel EA, Seitsonen J, Kontturi E, Scherman OA, Ikkala O (2014a) Healable, stable and stiff hydrogels: combining conflicting properties using dynamic and selective three-component recognition with reinforcing cellulose nanorods. Adv Funct Mater 24:2706–2713.  https://doi.org/10.1002/adfm.201303699 CrossRefGoogle Scholar
  25. McKee JR, Hietala S, Seitsonen J, Laine J, Kontturi E, Ikkala O (2014b) Thermoresponsive nanocellulose hydrogels with tunable mechanical properties. ACS Macro Lett 3:266–270.  https://doi.org/10.1021/mz400596g CrossRefGoogle Scholar
  26. Neal JA, Mozhdehi D, Guan Z (2015) Enhancing mechanical performance of a covalent self-healing material by sacrificial noncovalent bonds. J Am Chem Soc 137:4846–4850.  https://doi.org/10.1021/jacs.5b01601 CrossRefGoogle Scholar
  27. Patenaude M, Hoare T (2012) Injectable, degradable thermoresponsive poly(N-isopropylacrylamide) hydrogels. ACS Macro Lett 1:409–413.  https://doi.org/10.1021/mz200121k CrossRefGoogle Scholar
  28. Peng Y, Han B, Liu W, Xu X (2005) Preparation and antimicrobial activity of hydroxypropyl chitosan. Carbohydr Res 340:1846–1851.  https://doi.org/10.1016/j.carres.2005.05.009 CrossRefGoogle Scholar
  29. Sampath UGTM, Ching YC, Chuah CH, Singh R, Lin P-C (2017) Preparation and characterization of nanocellulose reinforced semi-interpenetrating polymer network of chitosan hydrogel. Cellulose 24:2215–2228.  https://doi.org/10.1007/s10570-017-1251-8 CrossRefGoogle Scholar
  30. Sanchez-Sanchez A, Pomposo JA (2014) Single–chain polymer nanoparticles via non-covalent and dynamic covalent bonds. Part Part Syst Charact 31:11–23.  https://doi.org/10.1002/ppsc.201300245 CrossRefGoogle Scholar
  31. Sanchez-Sanchez A, Fulton DA, Pomposo JA (2014) pH-responsive single-chain polymer nanoparticles utilising dynamic covalent enamine bonds. Chem Commun 50:1871–1874.  https://doi.org/10.1039/c3cc48733d CrossRefGoogle Scholar
  32. Sivakumaran D, Maitland D, Hoare T (2011) Injectable microgel-hydrogel composites for prolonged small-molecule drug delivery. Biomacromol 12:4112–4120.  https://doi.org/10.1021/bm201170h CrossRefGoogle Scholar
  33. Tseng T-C, Tao L, Hsieh F-Y, Wei Y, Chiu I-M, S-h Hsu (2015) An injectable, self-healing hydrogel to repair the central nervous system. Adv Mater 27:3518–3524.  https://doi.org/10.1002/adma.201500762 CrossRefGoogle Scholar
  34. Wei Z et al (2013) Dextran-based self-healing hydrogels formed by reversible diels-alder reaction under physiological conditions. Macromol Rapid Commun 34:1464–1470.  https://doi.org/10.1002/marc.201300494 CrossRefGoogle Scholar
  35. Wei Z et al (2015) Novel biocompatible polysaccharide-based self-healing hydrogel. Adv Funct Mater 25:1352–1359.  https://doi.org/10.1002/adfm.201401502 CrossRefGoogle Scholar
  36. Xing R et al (2016) An injectable self-assembling collagen-gold hybrid hydrogel for combinatorial antitumor photothermal/photodynamic therapy. Adv Mater 28:3669–3676.  https://doi.org/10.1002/adma.201600284 CrossRefGoogle Scholar
  37. Xue Y, Mou Z, Xiao H (2017) Nanocellulose as a sustainable biomass material: structure, properties, present status and future prospects in biomedical applications. Nanoscale 9:14758–14781.  https://doi.org/10.1039/c7nr04994c CrossRefGoogle Scholar
  38. Yan S et al (2014) Injectable in situ self-cross-linking hydrogels based on poly(l-glutamic acid) and alginate for cartilage tissue engineering. Biomacromol 15:4495–4508.  https://doi.org/10.1021/bm501313t CrossRefGoogle Scholar
  39. Yang X, Cranston ED (2014) Chemically cross-linked cellulose nanocrystal aerogels with shape recovery and superabsorbent properties. Chem Mater 26:6016–6025.  https://doi.org/10.1021/cm502873c CrossRefGoogle Scholar
  40. Yang J, Xu F (2017) Synergistic reinforcing mechanisms in cellulose nanofibrils composite hydrogels: interfacial dynamics, energy dissipation, and damage resistance. Biomacromol 18:2623–2632.  https://doi.org/10.1021/acs.biomac.7b00730 CrossRefGoogle Scholar
  41. Yang B, Zhang Y, Zhang X, Tao L, Li S, Wei Y (2012a) Facilely prepared inexpensive and biocompatible self-healing hydrogel: a new injectable cell therapy carrier. Polym Chem 3:3235–3238.  https://doi.org/10.1039/c2py20627g CrossRefGoogle Scholar
  42. Yang J, Han C-R, Duan J-F, Ma M-G, Zhang X-M, Xu F, Sun R-C (2012b) Synthesis and characterization of mechanically flexible and tough cellulose nanocrystals–polyacrylamide nanocomposite hydrogels. Cellulose 20:227–237.  https://doi.org/10.1007/s10570-012-9841-y CrossRefGoogle Scholar
  43. Yang X, Bakaic E, Hoare T, Cranston ED (2013) Injectable polysaccharide hydrogels reinforced with cellulose nanocrystals: morphology, rheology, degradation, and cytotoxicity. Biomacromol 14:4447–4455.  https://doi.org/10.1021/bm401364z CrossRefGoogle Scholar
  44. Yang J, Han C-R, Zhang X-M, Xu F, Sun R-C (2014a) Cellulose nanocrystals mechanical reinforcement in composite hydrogels with multiple cross-links: correlations between dissipation properties and deformation mechanisms. Macromolecules 47:4077–4086.  https://doi.org/10.1021/ma500729q CrossRefGoogle Scholar
  45. Yang J, Han CR, Xu F, Sun RC (2014b) Simple approach to reinforce hydrogels with cellulose nanocrystals. Nanoscale 6:5934–5943.  https://doi.org/10.1039/c4nr01214c CrossRefGoogle Scholar
  46. Yang J, Zhang X-M, Xu F (2015) Design of cellulose nanocrystals template-assisted composite hydrogels: insights from static to dynamic alignment. Macromolecules 48:1231–1239.  https://doi.org/10.1021/ma5026175 CrossRefGoogle Scholar
  47. Yang J, Xu F, Han CR (2017) Metal ion mediated cellulose nanofibrils transient network in covalently cross-linked hydrogels: mechanistic insight into morphology and dynamics. Biomacromol 18:1019–1028.  https://doi.org/10.1021/acs.biomac.6b01915 CrossRefGoogle Scholar
  48. Yesilyurt V, Webber MJ, Appel EA, Godwin C, Langer R, Anderson DG (2016) Injectable self-healing glucose-responsive hydrogels with pH-regulated mechanical properties. Adv Mater 28:86–91.  https://doi.org/10.1002/adma.201502902 CrossRefGoogle Scholar
  49. Yu L, Ding J (2008) Injectable hydrogels as unique biomedical materials. Chem Soc Rev 37:1473–1481.  https://doi.org/10.1039/b713009k CrossRefGoogle Scholar
  50. Zhang Y, Fu C, Li Y, Wang K, Wang X, Wei Y, Tao L (2017) Synthesis of an injectable, self-healable and dual responsive hydrogel for drug delivery and 3D cell cultivation. Polym Chem 8:537–544.  https://doi.org/10.1039/c6py01704e CrossRefGoogle Scholar

Copyright information

© Springer Science+Business Media B.V., part of Springer Nature 2017

Authors and Affiliations

  • Hongchen Liu
    • 1
  • Chaojing Li
    • 2
  • Bijia Wang
    • 1
  • Xiaofeng Sui
    • 1
  • Lu Wang
    • 2
  • Xiaolin Yan
    • 3
  • Hong Xu
    • 1
  • Linping Zhang
    • 1
  • Yi Zhong
    • 1
  • Zhiping Mao
    • 1
  1. 1.Key Lab of Science and Technology of Eco-textile, Ministry of Education, College of Chemistry, Chemical Engineering and BiotechnologyDonghua UniversityShanghaiPeople’s Republic of China
  2. 2.Key Lab of Textile Science and Technology, Ministry of EducationDonghua UniversityShanghaiPeople’s Republic of China
  3. 3.Inner Mongolia Agricultural UniversityHohhotPeople’s Republic of China

Personalised recommendations