Skip to main content
Log in

Hemicellulose-reinforced nanocellulose hydrogels for wound healing application

  • Original Paper
  • Published:
Cellulose Aims and scope Submit manuscript

Abstract

Polysaccharides are finding an increasing number of applications in medical and pharmaceutical fields thanks to their biodegradability, biocompatibility, and in some cases bioactivity. Two approaches were applied to use hemicelluloses as crosslinkers to tune the structural and mechanical properties of nanofibrillated cellulose (NFC) hydrogel scaffolds, and thus to investigate the effect of these properties on the cellular behavior during wound healing application. Different types of hemicellulose (galactoglucomannan (GGM), xyloglucan (XG), and xylan) were introduced into the NFC network via pre-sorption (Method I) and in situ adsorption (Method II) to reinforce the NFC hydrogels. The charge density of the NFC, the incorporated hemicellulose type and amount, and the swelling time of the hydrogels were found to affect the pore structure, the mechanical strength, and thus the cells’ growth on the composite hydrogel scaffolds. The XG showed the highest adsorption capacity on the NFC, the highest reinforcement effect, and facilitated/promoted cell growth. The pre-sorbed XG in the low-charged NFC network with a lower weight ratio (NFC/XG-90:10) showed the highest efficacy in supporting the growth and proliferation of fibroblast cells (NIH 3T3). These all-polysaccharide composite hydrogels may work as promising scaffolds in wound healing applications to provide supporting networks and to promote cells adhesion, growth, and proliferation.

This is a preview of subscription content, log in via an institution to check access.

Access this article

Price excludes VAT (USA)
Tax calculation will be finalised during checkout.

Instant access to the full article PDF.

Institutional subscriptions

Fig. 1
Fig. 2
Fig. 3
Fig. 4
Fig. 5
Fig. 6

Similar content being viewed by others

References

  • Alexandrescu L, Syverud K, Gatti A, Chinga-Carrasco G (2013) Cytotoxicity tests of cellulose nanofibril-based structures. Cellulose 20:1765–1775. doi:10.1007/s10570-013-9948-9

    Article  CAS  Google Scholar 

  • Andrijevic L, Radotic K, Bogdanovic J, Mutavdzic D, Bogdanovic G (2008) Antiproliferative effect of synthetic lignin against human breast cancer and normal fetal lung cell lines. Potency of low molecular weight fractions. J BUON 13:241–244

    Google Scholar 

  • Balakrishnan B, Banerjee R (2011) Biopolymer-based hydrogels for cartilage tissue engineering. Chem Rev 111:4453–4474. doi:10.1021/cr100123h

    Article  CAS  Google Scholar 

  • Barbucci R (2009) Hydrogels: biological properties and applications. Springer, Milan

    Book  Google Scholar 

  • Bhattacharya M et al (2012) Nanofibrillar cellulose hydrogel promotes three-dimensional liver cell culture. J Controll Release 164:291–298. doi:10.1016/j.jconrel.2012.06.039

    Article  CAS  Google Scholar 

  • Bodin A, Ahrenstedt L, Fink H, Brumer H, Risberg B, Gatenholm P (2007) Modification of nanocellulose with a xyloglucan-RGD conjugate enhances adhesion and proliferation of endothelial cells: implications for tissue engineering. Biomacromolecules 8:3697–3704. doi:10.1021/bm070343q

    Article  CAS  Google Scholar 

  • Bonilla MR, Lopez-Sanchez P, Gidley MJ, Stokes JR (2015) Micromechanical model of biphasic biomaterials with internal adhesion: application to nanocellulose hydrogel composites. Acta Biomater. doi:10.1016/j.actbio.2015.10.032

    Google Scholar 

  • Borges AC et al (2011) Nanofibrillated cellulose composite hydrogel for the replacement of the nucleus pulposus. Acta Biomater 7:3412–3421. doi:10.1016/j.actbio.2011.05.029

    Article  CAS  Google Scholar 

  • Cartmell SH, Thurstan S, Gittings JP, Griffiths S, Bowen CR, Turner IG (2014) Polarization of porous hydroxyapatite scaffolds: influence on osteoblast cell proliferation and extracellular matrix production. J Biomed Mater Res Part A 102:1047–1052. doi:10.1002/jbm.a.34790

    Article  CAS  Google Scholar 

  • Chang H-I, Wang Y (2011) Cell responses to surface and architecture of tissue engineering scaffolds. In: Daniel E (ed) Regenerative medicine and tissue engineering—cells and biomaterials. InTech, Croatla. doi:10.5772/21983

  • Chinga-Carrasco G, Syverud K (2014) Pretreatment-dependent surface chemistry of wood nanocellulose for pH-sensitive hydrogels. J Biomater Appl 29:423–432. doi:10.1177/0885328214531511

    Article  Google Scholar 

  • Chinga-Carrasco G, Averianova N, Kondalenko O, Garaeva M, Petrov V, Leinsvang B, Karlsen T (2014) The effect of residual fibres on the micro-topography of cellulose nanopaper. Micron 56:80–84. doi:10.1016/j.micron.2013.09.002

    Article  CAS  Google Scholar 

  • Czaja WK, Young DJ, Kawecki M, Brown RM Jr (2007) The future prospects of microbial cellulose in biomedical applications. Biomacromolecules 8:1–12. doi:10.1021/bm060620d

    Article  CAS  Google Scholar 

  • Eckardt NA (2008) Role of xyloglucan in primary cell walls. Plant Cell 20:1421–1422. doi:10.1105/tpc.108.061382

    Article  CAS  Google Scholar 

  • Eisenbarth E, Meyle J, Nachtigall W, Breme J (1996) Influence of the surface structure of titanium materials on the adhesion of fibroblasts. Biomaterials 17:1399–1403

    Article  CAS  Google Scholar 

  • Eronen P, Osterberg M, Heikkinen S, Tenkanen M, Laine J (2011a) Interactions of structurally different hemicelluloses with nanofibrillar cellulose. Carbohydr Polym 86:1281–1290. doi:10.1016/j.carbpol.2011.06.031

    Article  CAS  Google Scholar 

  • Eronen P, Österberg M, Heikkinen S, Tenkanen M, Laine J (2011b) Interactions of structurally different hemicelluloses with nanofibrillar cellulose. Carbohydr Polym 86:1281–1290. doi:10.1016/j.carbpol.2011.06.031

    Article  CAS  Google Scholar 

  • Fukuzumi H, Saito T, Iwata T, Kumamoto Y, Isogai A (2009) Transparent and high gas barrier films of cellulose nanofibers prepared by TEMPO-mediated oxidation. Biomacromolecules 10:162–165. doi:10.1021/bm801065u

    Article  CAS  Google Scholar 

  • George JT, Howard G (1963) Quantitative studies of the growth of mouse embryo cells in culture and their development into established lines. J Cell Biol 17:15. doi:10.1083/jcb.17.2.299

    Google Scholar 

  • Goldschmid O (1954) Determination of phenolic hydroxyl content of lignin preparations by ultraviolet spectrophotometry. Anal Chem 26:1421–1423

    Article  CAS  Google Scholar 

  • Holback H, Yeo Y, Park K (2011) Hydrogel swelling behavior and its biomedical applications. In: Rimmer S (ed) Biomedical hydrogels. Woodhead Publishing, UK, pp 3–24

    Chapter  Google Scholar 

  • Hua K, Carlsson DO, Ålander E, Lindström T, Strømme M, Mihranyan A, Ferraz N (2014) Translational study between structure and biological response of nanocellulose from wood and green algae. RSC Adv 4:2892–2903. doi:10.1039/c3ra45553j

    Article  CAS  Google Scholar 

  • Itoh S, Nakamura S, Nakamura M, Shinomiya K, Yamashita K (2006) Enhanced bone ingrowth into hydroxyapatite with interconnected pores by Electrical Polarization. Biomaterials 27:5572–5579. doi:10.1016/j.biomaterials.2006.07.007

    Article  CAS  Google Scholar 

  • Janmey PA, Miller RT (2011) Mechanisms of mechanical signaling in development and disease. J Cell Sci 124:9–18. doi:10.1242/jcs.071001

    Article  CAS  Google Scholar 

  • Johansson P et al (2004) Crystal structures of a poplar xyloglucan endotransglycosylase reveal details of transglycosylation acceptor binding. Plant cell 16:874–886. doi:10.1105/tpc.020065

    Article  CAS  Google Scholar 

  • Kabel MA, van den Borne H, Vincken JP, Voragen AGJ, Schols HA (2007) Structural differences of xylans affect their interaction with cellulose. Carbohydr Polym 69:94–105

    Article  CAS  Google Scholar 

  • Karaaslan MA, Tshabalala MA, Yelle DJ, Buschle-Diller G (2011) Nanoreinforced biocompatible hydrogels from wood hemicelluloses and cellulose whiskers. Carbohydr Polym 86:192–201. doi:10.1016/j.carbpol.2011.04.030

    Article  CAS  Google Scholar 

  • Kilpeläinen P, Kitunen V, Pranovich A, Ilvesniemi H, Willfor S (2013) Pressurized Hot Water Flow-through Extraction of Birch Sawdust with Acetate pH Buffer. Bioresources 8:5202–5218

    Article  Google Scholar 

  • Lin S, Sangaj N, Razafiarison T, Zhang C, Varghese S (2011) Influence of physical properties of biomaterials on cellular behavior. Pharm Res 28:1422–1430. doi:10.1007/s11095-011-0378-9

    Article  CAS  Google Scholar 

  • Linder A, Bergman R, Bodin A, Gatenholm P (2003) Mechanism of assembly of xylan onto cellulose surfaces. Langmuir ACS J Surf Colloids 19:5072–5077

    Article  CAS  Google Scholar 

  • Liu J, Korpinen R, Mikkonen K, Willför S, Xu C (2014) Nanofibrillated cellulose originated from birch sawdust after sequential extractions: a promising polymeric material from waste to films. Cellulose 21:2587–2598. doi:10.1007/s10570-014-0321-4

    Article  CAS  Google Scholar 

  • Liu J, Willför S, Xu C (2015) A review of bioactive plant polysaccharides: biological activities, functionalization, and biomedical applications. Bioact Carbohydr Diet Fibre 5:31–61

    Article  CAS  Google Scholar 

  • Liu J et al (2016) Development of nanocellulose scaffolds with tunable structures to support 3D cell culture. Carbohydr Polym 148:259–271

    Article  CAS  Google Scholar 

  • Lopez-Sanchez P, Cersosimo J, Wang D, Flanagan B, Stokes JR, Gidley MJ (2015) Poroelastic mechanical effects of hemicelluloses on cellulosic hydrogels under compression. PLOS One 10:e0122132. doi:10.1371/journal.pone.0122132

    Article  Google Scholar 

  • Lucenius J, Parikka K, Österberg M (2014) Nanocomposite films based on cellulose nanofibrils and water-soluble polysaccharides. React Funct Polym 85:167–174. doi:10.1016/j.reactfunctpolym.2014.08.001

    Article  CAS  Google Scholar 

  • Malinen MM, Kanninen LK, Corlu A, Isoniemi HM, Lou Y-R, Yliperttula ML, Urtti AO (2014) Differentiation of liver progenitor cell line to functional organotypic cultures in 3D nanofibrillar cellulose and hyaluronan-gelatin hydrogels. Biomaterials 35:5110–5121. doi:10.1016/j.biomaterials.2014.03.020

    Article  CAS  Google Scholar 

  • Martinez-Ruvalcaba A (2008) Swelling characterization and drug delivery kinetics of polyacrylamide-co-itaconic acid/chitosan hydrogels eXPRESS. Polym Lett 3:25–32. doi:10.3144/expresspolymlett.2009.5

    Article  Google Scholar 

  • Mehling T, Smirnova I, Guenther U, Neubert RHH (2009) Polysaccharide-based aerogels as drug carriers. J Non-Cryst Solids 355:2472–2479. doi:10.1016/j.jnoncrysol.2009.08.038

    Article  CAS  Google Scholar 

  • Mertaniemi H et al (2016) Human stem cell decorated nanocellulose threads for biomedical applications. Biomaterials 82:208–220. doi:10.1016/j.biomaterials.2015.12.020

    Article  CAS  Google Scholar 

  • Moroni L, de Wijn JR, van Blitterswijk CA (2006) 3D fiber-deposited scaffolds for tissue engineering: influence of pores geometry and architecture on dynamic mechanical properties. Biomaterials 27:974–985. doi:10.1016/j.biomaterials.2005.07.023

    Article  CAS  Google Scholar 

  • Muiznieks LD, Keeley FW (2013) Molecular assembly and mechanical properties of the extracellular matrix: a fibrous protein perspective. Biochim Biophys Acta 1832:866–875. doi:10.1016/j.bbadis.2012.11.022

    Article  CAS  Google Scholar 

  • Okay O (2010) General properties of hydrogels. In: Gerlach G, Arndt K-F (eds) Hydrogel sensors and actuators, vol vol 6., Springer Series on Chemical Sensors and BiosensorsSpringer, Heidelberg, pp 1–14. doi:10.1007/978-3-540-75645-3_1

    Chapter  Google Scholar 

  • Park YB, Cosgrove DJ (2015) Xyloglucan and its interactions with other components of the growing cell wall. Plant Cell Physiol 56:180–194

    Article  Google Scholar 

  • Pereira MM et al (2013) Cytotoxicity and expression of genes involved in the cellular stress response and apoptosis in mammalian fibroblast exposed to cotton cellulose nanofibers. Nanotechnology 24

  • Petersen N, Gatenholm P (2011) Bacterial cellulose-based materials and medical devices: current state and perspectives. Appl Microbiol Biotechnol 91:1277–1286. doi:10.1007/s00253-011-3432-y

    Article  CAS  Google Scholar 

  • Plant AL, Bhadriraju K, Spurlin TA, Elliott JT (2009) Cell response to matrix mechanics: focus on collagen. Biochim Biophys Acta (BBA)—Mol Cell Res 1793:893–902. doi:10.1016/j.bbamcr.2008.10.012

    Article  CAS  Google Scholar 

  • Popa V (2011) Polysaccharides in medicinal and pharmaceutical applications. Smithers Rapra, Shrewsbury

    Google Scholar 

  • Portal O, Clark WA, Levinson DJ (2009) Microbial cellulose wound dressing in the treatment of nonhealing lower extremity ulcers. Wounds 21:1–3

    Google Scholar 

  • Powell LC, Khan S, Chinga-Carrasco G, Wright CJ, Hill KE, Thomas DW (2016) An investigation of Pseudomonas aeruginosa biofilm growth on novel nanocellulose fibre dressings. Carbohydr Polym 137:191–197. doi:10.1016/j.carbpol.2015.10.024

    Article  CAS  Google Scholar 

  • Prakobna K, Kisonen V, Xu C, Berglund L (2015) Strong reinforcing effects from galactoglucomannan hemicellulose on mechanical behavior of wet cellulose nanofiber gels. J Mater Sci 50:7413–7423. doi:10.1007/s10853-015-9299-z

    Article  CAS  Google Scholar 

  • Richards RG (1996) The effect of surface roughness on fibroblast adhesion in vitro. Injury 27(Suppl 3):SC38–43

    Google Scholar 

  • Rimmer SD (2011) Biomedical hydrogels: biochemistry, manufacture and medical applications. Woodhead Pub, Oxford

    Book  Google Scholar 

  • Rosario P (2013) Advances in biomaterials science and biomedical applications. InTech. doi:10.5772/56420

  • Saddiq ZA, Barbenel JC, Grant MH (2009) The mechanical strength of collagen gels containing glycosaminoglycans and populated with fibroblasts. J Biomed Mater Res Part A 89A:697–706. doi:10.1002/jbm.a.32007

    Article  CAS  Google Scholar 

  • Saito T, Nishiyama Y, Putaux J-L, Vignon M, Isogai A (2006) Homogeneous suspensions of individualized microfibrils from TEMPO-catalyzed oxidation of native cellulose. Biomacromolecules 7:1687–1691. doi:10.1021/bm060154s

    Article  CAS  Google Scholar 

  • Sehaqui H, Zhou Q, Berglund LA (2011) High-porosity aerogels of high specific surface area prepared from nanofibrillated cellulose (NFC). Compos Sci Technol 71:1593–1599. doi:10.1016/j.compscitech.2011.07.003

    Article  CAS  Google Scholar 

  • Simkovic I (2013) Unexplored possibilities of all-polysaccharide composites. Carbohydr Polym 95:697–715. doi:10.1016/j.carbpol.2013.03.040

    Article  CAS  Google Scholar 

  • Sorimachi K, Watanabe K, Yamazaki S, Yasumura Y (1992) Inhibition of fibroblast growth by polyanions; effects of dextran sulfate and lignin derivatives. Cell Biol Int Rep 16:63–71

    Article  CAS  Google Scholar 

  • Stevanic JS, Mikkonen KS, Xu CL, Tenkanen M, Berglund L, Salmen L (2014) Wood cell wall mimicking for composite films of spruce nanofibrillated cellulose with spruce galactoglucomannan and arabinoglucuronoxylan. J Mater Sci 49:5043–5055

    Article  CAS  Google Scholar 

  • Syverud K, Chinga-Carrasco G, Toledo J, Toledo PG (2011) A comparative study of Eucalyptus and Pinus radiata pulp fibres as raw materials for production of cellulose nanofibrils. Carbohydr Polym 84:1033–1038. doi:10.1016/j.carbpol.2010.12.066

    Article  CAS  Google Scholar 

  • Syverud K, Pettersen S, Draget K, Chinga-Carrasco G (2014) Controlling the elastic modulus of cellulose nanofibril hydrogels—scaffolds with potential in tissue engineering. Cellulose 1–9 doi:10.1007/s10570-014-0470-5

  • Syverud K, Pettersen S, Draget K, Chinga-Carrasco G (2015) Controlling the elastic modulus of cellulose nanofibril hydrogels—scaffolds with potential in tissue engineering. Cellulose 22:473–481. doi:10.1007/s10570-014-0470-5

    Article  CAS  Google Scholar 

  • Wells RG (2008) The role of matrix stiffness in regulating cell behavior. Hepatology 47:1394–1400. doi:10.1002/hep.22193

    Article  CAS  Google Scholar 

  • Wells RG (2013) Tissue mechanics and fibrosis. Biochim Biophys Acta 1832:884–890. doi:10.1016/j.bbadis.2013.02.007

    Article  CAS  Google Scholar 

  • Willför S, Rehn P, Sundberg A, Sundberg K, Holmbom B (2003) Recovery of water-soluble acetylgalactoglucomannans from mechanical pulp of spruce. TAPPI J 2:27–32

    Google Scholar 

  • Xu C, Leppanen AS, Eklund P, Holmlund P, Sjoholm R, Sundberg K, Willfor S (2010) Acetylation and characterization of spruce (Picea abies) galactoglucomannans. Carbohydr Res 345:810–816. doi:10.1016/j.carres.2010.01.007

    Article  CAS  Google Scholar 

  • Xu C, Spadiut O, Araújo AC, Nakhai A, Brumer H (2012) Chemo-enzymatic assembly of clickable cellulose surfaces via multivalent polysaccharides. ChemSusChem 5:661–665. doi:10.1002/cssc.201100522

    Article  CAS  Google Scholar 

  • Yang T, Malkoch M, Hult A (2013) Sequential interpenetrating poly(ethylene glycol) hydrogels prepared by UV-initiated thiol–ene coupling chemistry. J Polym Sci, Part A Polym Chem 51:363–371. doi:10.1002/pola.26393

    Article  CAS  Google Scholar 

Download references

Acknowledgments

Jun Liu would like to acknowledge the financial support of the China Scholarship Council and Graduate School of Chemical Engineering of Åbo Akademi University. This work is also part of the activities at the Johan Gadolin Process Chemistry Centre, a Centre of Excellence appointed by Åbo Akademi University. NordForsk via the Refining Lignocellulosics to Advanced Polymers and Fibers (PolyRefNorth) network and the NORCEL project (Grant No. 228147) and NanoHeal project (Grant No. 219733), funded by the Research Council of Norway through the NANO2021 Program, are thanked for supporting the research exchange of Jun Liu at PFI. The Research Council of Norway is also acknowledged for the support to the Norwegian Micro- and Nano-Fabrication Facility, NorFab (Grant No. 197411/V30), which facilitated the AFM analysis. Ingebjorg Leirset, Per Olav Johnsen, Anne Reitan, Mirjana Filipovic, Storker Mor, and all other colleagues at PFI are acknowledged for assistance of the laboratory work.

Author information

Authors and Affiliations

Authors

Corresponding authors

Correspondence to Kristin Syverud or Chunlin Xu.

Electronic supplementary material

Below is the link to the electronic supplementary material.

Supplementary material 1 (DOC 12,307 kb)

Rights and permissions

Reprints and permissions

About this article

Check for updates. Verify currency and authenticity via CrossMark

Cite this article

Liu, J., Chinga-Carrasco, G., Cheng, F. et al. Hemicellulose-reinforced nanocellulose hydrogels for wound healing application. Cellulose 23, 3129–3143 (2016). https://doi.org/10.1007/s10570-016-1038-3

Download citation

  • Received:

  • Accepted:

  • Published:

  • Issue Date:

  • DOI: https://doi.org/10.1007/s10570-016-1038-3

Keywords

Navigation