BioChip Journal

, Volume 7, Issue 3, pp 201–209 | Cite as

Evaluation of immunoreactivity of in vitro and in vivo models against bacterial synthesized cellulose to be used as a prosthetic biomaterial

  • Gun-Dong Kim
  • Hana Yang
  • Hye Rim Park
  • Cheung-Seog Park
  • Yong Seek ParkEmail author
  • Seung Eun LeeEmail author
Original Article


Prosthetic biomaterials are required to be non-toxic, non-thrombogenic, and non-immunogenic. Bacterial cellulose (BC) synthesized by Gluconacetobacter xylinus has recently been studied as a biocompatible material due to its unique features such as high purity, crystallinity, biodegradability, and tensile strength as compared to plant cellulose. Although BC has high potential to be used as biomaterial, its toxicity and immunoreactivity have not been properly studied yet. In this report, we investigated the immunoreactivity of BC in vitro in human umbilical vein endothelial cells (HUVECs) and in vivo using BALB/c mice. We report that BC does not induce apoptosis and necrosis in HUVECs and does not stimulate immune response in both HUVECs and BALB/c mice models. These results suggest that BC may be widely used as a biocompatible biomaterial for tissue engineering and biosensors.


Gluconacetobacter xylinus Bacterial cellulose (BC) Biomaterials Immunoreactivity Human umbilical vein endothelial cells (HUVECs) Lipopolysaccharide (LPS) 


Unable to display preview. Download preview PDF.

Unable to display preview. Download preview PDF.


  1. 1.
    Petersen, N. & Gatenholm, P. Bacterial cellulose-based materials and medical devices: current state and perspectives. Appl. Microbiol. Biotechnol. 91, 1277–1286 (2011).CrossRefGoogle Scholar
  2. 2.
    Klemm, D. et al. Nanocelluloses: A New Family of Nature-Based Materials. Angewandte Chemie-International Edition 50, 5438–5466 (2011).CrossRefGoogle Scholar
  3. 3.
    Kim, S.Y. et al. Production of bacterial cellulose by Gluconacetobacter sp. RKY5 isolated from persimmon vinegar. Appl. Biochem. Biotechnol. 131, 705–715 (2006).CrossRefGoogle Scholar
  4. 4.
    Falcao, S.C., Coelho, A.R. & Evencio Neto, J. Biomechanical evaluation of microbial cellulose (Zoogloea sp.) and expanded polytetrafluoroethylene membranes as implants in repair of produced abdominal wall defects in rats. Acta Cir. Bras. 23, 184–191 (2008).CrossRefGoogle Scholar
  5. 5.
    Brown, R.M., Jr., Willison, J.H. & Richardson, C.L. Cellulose biosynthesis in Acetobacter xylinum: visualization of the site of synthesis and direct measurement of the in vivo process. Proc. Natl. Acad. Sci. USA 73, 4565–4569 (1976).CrossRefGoogle Scholar
  6. 6.
    Ross, P., Mayer, R. & Benziman, M. Cellulose biosynthesis and function in bacteria. Microbiol. Rev. 55, 35–58 (1991).Google Scholar
  7. 7.
    Hutchens, S.A. et al. Biomimetic synthesis of calciumdeficient hydroxyapatite in a natural hydrogel. Biomaterials 27, 4661–4670 (2006).CrossRefGoogle Scholar
  8. 8.
    Helenius, G. et al. In vivo biocompatibility of bacterial cellulose. J. Biomed. Mater. Res. A. 76, 431–438 (2006).Google Scholar
  9. 9.
    Muller, D. et al. Structure and properties of polypyrrole/bacterial cellulose nanocomposites. Carbohydrate Polymers 94, 655–662 (2013).CrossRefGoogle Scholar
  10. 10.
    Teeri, T.T., Brumer, H., 3rd, Daniel, G. & Gatenholm, P. Biomimetic engineering of cellulose-based materials. Trends Biotechnol. 25, 299–306 (2007).CrossRefGoogle Scholar
  11. 11.
    Czaja, W., Krystynowicz, A., Bielecki, S. & Brown, R.M., Jr. Microbial cellulose — the natural power to heal wounds. Biomaterials 27, 145–151 (2006).CrossRefGoogle Scholar
  12. 12.
    Liang, Y. et al. A novel bacterial cellulose-based carbon paste electrode and its polyoxometalate-modified properties. Electrochemistry Communications 11, 1018–1021 (2009).CrossRefGoogle Scholar
  13. 13.
    Jeong, S.I. et al. Effect of alpha,beta-unsaturated aldehydes on endothelial cell growth in bacterial cellulose for vascular tissue engineering. Mol. Cell. Toxicol. 8, 119–126 (2012).CrossRefGoogle Scholar
  14. 14.
    Schumann, D.A. et al. Artificial vascular implants from bacterial cellulose: preliminary results of small arterial substitutes. Cellulose 16, 877–885 (2009).CrossRefGoogle Scholar
  15. 15.
    Klemm, D., Schumann, D., Udhardt, U. & Marsch, S. Bacterial synthesized cellulose — artificial blood vessels for microsurgery. Progress in Polymer Science 26, 1561–1603 (2001).CrossRefGoogle Scholar
  16. 16.
    Schumann, D.A. et al. New results about BASYC (R) (bacterial synthesized cellulose), the promising artificial blood vessel for microsurgery and further application of bacterial cellulose in medicine. Abstracts of Papers of the American Chemical Society 229, U300–U300 (2005).Google Scholar
  17. 17.
    Backdahl, H. et al. Mechanical properties of bacterial cellulose and interactions with smooth muscle cells. Biomaterials 27, 2141–2149 (2006).CrossRefGoogle Scholar
  18. 18.
    Lau, R.K.L. et al. Mechanical characterization of cellulosic thecal plates in dinoflagellates by nanoindentation. Journal of Nanoscience and Nanotechnology 7, 452–457 (2007).Google Scholar
  19. 19.
    Habibovic, P. et al. 3D microenvironment as essential element for osteoinduction by biomaterials. Biomaterials 26, 3565–3575 (2005).CrossRefGoogle Scholar
  20. 20.
    Fink, H. et al. An in vitro study of blood compatibility of vascular grafts made of bacterial cellulose in comparison with conventionally-used graft materials. Journal of Biomedical Materials Research Part A 97A, 52–58 (2011).CrossRefGoogle Scholar
  21. 21.
    Wang, B. & Dong, S. Sol-gel-derived amperometric biosensor for hydrogen peroxide based on methylene green incorporated in Nafion film. Talanta 51, 565–572 (2000).CrossRefGoogle Scholar
  22. 22.
    Salomao, R. et al. Bacterial Sensing, Cell Signaling, and Modulation of the Immune Response during Sepsis. Shock 38, 227–242 (2012).CrossRefGoogle Scholar
  23. 23.
    Zhao, Q.T., Guo, Q.M., Wang, P. & Wang, Q. Salvianic acid A inhibits lipopolysaccharide-induced apoptosis through regulating glutathione peroxidase activity and malondialdehyde level in vascular endothelial cells. Chinese Journal of Natural Medicines 10, 53–57 (2012).CrossRefGoogle Scholar
  24. 24.
    Galanos, C. et al. Biological activities of lipopolysaccharides and lipid A from Rhodospirillaceae. Infect. Immun. 16, 407–412 (1977).Google Scholar
  25. 25.
    Mackensen, A., Galanos, C. & Engelhardt, R. Modulating Activity of Interferon-Gamma on Endotoxin-Induced Cytokine Production in Cancer-Patients. Blood 78, 3254–3258 (1991).Google Scholar
  26. 26.
    Dimmeler, S. & Zeiher, A.M. Endothelial cell apoptosis in angiogenesis and vessel regression. Circ. Res. 87, 434–439 (2000).CrossRefGoogle Scholar
  27. 27.
    Munoz, C. et al. Dysregulation of in vitro cytokine production by monocytes during sepsis. J. Clin. Invest. 88, 1747–1754 (1991).CrossRefGoogle Scholar
  28. 28.
    De Beaux, A.C. et al. Interleukin-4 and interleukin-10 increase endotoxin-stimulated human umbilical vein endothelial cell interleukin-8 release. J. Interferon. Cytokine Res. 15, 441–445 (1995).CrossRefGoogle Scholar
  29. 29.
    Le, J., Lin, J.X., Henriksen-DeStefano, D. & Vilcek, J. Bacterial lipopolysaccharide-induced interferongamma production: roles of interleukin 1 and interleukin 2. J. Immunol. 136, 4525–4530 (1986).Google Scholar
  30. 30.
    Eliopoulos, A.G. et al. Induction of COX-2 by LPS in macrophages is regulated by Tpl2-dependent CREB activation signals. EMBO J. 21, 4831–4840 (2002).CrossRefGoogle Scholar
  31. 31.
    Park, Y.S. et al. Acrolein induces cyclooxygenase-2 and prostaglandin production in human umbilical vein endothelial cells: roles of p38 MAP kinase. Arterioscler Thromb Vasc Biol. 27, 1319–1325 (2007).CrossRefGoogle Scholar
  32. 32.
    Caughey, G.E. et al. Roles of cyclooxygenase (COX)-1 and COX-2 in prostanoid production by human endothelial cells: selective up-regulation of prostacyclin synthesis by COX-2. J. Immunol. 167, 2831–2838 (2001).Google Scholar
  33. 33.
    Tough, D.F., Sun, S. & Sprent, J. T cell stimulation in vivo by lipopolysaccharide (LPS). J. Exp. Med. 185, 2089–2094 (1997).CrossRefGoogle Scholar
  34. 34.
    Yang, H.Y., Dundon, P.L., Nahill, S.R. & Welsh, R.M. Virus-induced polyclonal cytotoxic T lymphocyte stimulation. J. Immunol. 142, 1710–1718 (1989).Google Scholar
  35. 35.
    Wang, L. et al. High dose lipopolysaccharide triggers polarization of mouse thymic Th17 cells in vitro in the presence of mature dendritic cells. Cellular Immunology 274, 98–108 (2012).CrossRefGoogle Scholar
  36. 36.
    O’Sullivan, S.T. et al. Major injury leads to predominance of the T helper-2 lymphocyte phenotype and diminished interleukin-12 production associated with decreased resistance to infection. Ann. Surg. 222, 482–490; discussion 490–482 (1995).Google Scholar
  37. 37.
    Jeong, S.I. et al. Toxicologic evaluation of bacterial synthesized cellulose in endothelial cells and animals. Mol. Cell. Toxicol. 6, 373–380 (2010).CrossRefGoogle Scholar
  38. 38.
    Lee, S.E. et al. Upregulation of heme oxygenase-1 as an adaptive mechanism for protection against crotonaldehyde in human umbilical vein endothelial cells. Toxicology Letters 201, 240–248 (2011).CrossRefGoogle Scholar
  39. 39.
    Jeong, S.I. et al. Genome-wide analysis of gene expression by crotonaldehyde in human umbilical vein endothelial cells. Mol. Cell. Toxicol. 7, 127–134 (2011).CrossRefGoogle Scholar
  40. 40.
    Yang, H. et al. Up-regulation of Heme Oxygenase-1 by Korean Red Ginseng Water Extract as a Cytoprotective Effect in Human Endothelial Cells. Journal of Ginseng Research 35, 352–359 (2011).CrossRefGoogle Scholar

Copyright information

© The Korean BioChip Society and Springer-Verlag Berlin Heidelberg 2013

Authors and Affiliations

  1. 1.Department of Microbiology, School of MedicineKyung Hee UniversityHoegi-dong, Dongdaemun-gu, SeoulKorea

Personalised recommendations