Skip to main content
SpringerLink
Log in

Preparation and cytocompatibility evaluation for hydrosoluble phosphorous acid-derivatized cellulose as tissue engineering scaffold material

  • Published:
Journal of Materials Science: Materials in Medicine Aims and scope Submit manuscript

Abstract

Chemical modification of cellulose by phosphorylation enhances its bioactivity and provides new derivatives and materials with specific end uses. In the present study, cellulose derivatized with phosphorous acid was obtained using the reaction of microcrystalline cellulose with phosphorous acid–urea mixture, in molten state, in comparison with others methods that used different solvents and catalysts. Completely water soluble films with a substitution degree close to one were obtained and characterized by analytical and spectral analysis (FT-IR, 31P NMR), contact angle, metallographic microscopy and atomic force microscopy (AFM). 31P NMR spectra of derivatized cellulose showed a signal at 2.58 ppm (assigned to P–O–C6) while the doublets at 4.99–5.29 and at 7.38 ppm were assigned to P–O–C2 and P–O–C3, respectively; thus, the formation of monosubstituted phosphorous acid esters of cellulose is advocated. Contact angle measurements showed that the work of adhesion is more important in water than in ethylene glycol, for the phosphorous acid derivatized cellulose. The cytocompatibility of this hydrosoluble derivatized cellulose was tested by direct contact and also by indirect assays on normal human dermal fibroblasts and on osteoblast-like cells (human osteosarcoma). Cell growth on phosphorylated cellulose pellicle and the results from viability assays had shown a good cytocompatibility and lack of toxicity. Phosphorous acid derivatized cellulose would offer a promising biomaterial, useful as scaffolds for new biopolymer composites, and subject for further development as an ionic crosslinker.

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

Access this article

Log in via an institution

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
Fig. 7
Fig. 8

Similar content being viewed by others

References

  1. Enderle JD, Blanchard SM, Bronzino JD. Introduction to biomedical engineering. San Diego: Academic Press; 2000.

    Google Scholar 

  2. Kennedy JF, Phillips GO, Williams PA, Cellucon Conferences (Organization), Sen’i Gakkai (Japan). Cellulose : structural and functional aspects. Ellis Horwood series in polymer science and technology. Chichester/New York: Ellis Horwood/Halsted Press; 1989.

  3. Märtson M, Viljanto J, Hurme T, Laippala P, Saukko P. Is cellulose sponge degradable or stable as implantation material? An in vivo subcutaneous study in the rat. Biomaterials. 1999;20(21):1989–95. doi:10.1016/s0142-9612(99)00094-0.

    Article  Google Scholar 

  4. Granja PL, De Jeso B, Bareille R, Rouais F, Baquey C, Barbosa MA. Mineralization of regenerated cellulose hydrogels induced by human bone marrow stromal cells. Eur Cell Mater. 2005;10:31–7; discussion 7–9.

    Google Scholar 

  5. Barbosa MA, Granja PL, Barrias CC, Amaral IF. Polysaccharides as scaffolds for bone regeneration. ITBM-RBM. 2005;26(3):212–7. doi:10.1016/j.rbmret.2005.04.006.

    Article  Google Scholar 

  6. Barbié C, Chauveaux D, Barthe X, Baquey C, Poustis J. Biological behaviour of cellulosic materials after bone implantation: preliminary results. Clin Mater. 1990;5(2–4):251–8. doi:10.1016/0267-6605(90)90023-o.

    Article  Google Scholar 

  7. Granja PL, Pouységu L, Pétraud M, De Jéso B, Baquey C, Barbosa MA. Cellulose phosphates as biomaterials. I. Synthesis and characterization of highly phosphorylated cellulose gels. J Appl Polym Sci. 2001;82(13):3341–53. doi:10.1002/app.2193.

    Article  Google Scholar 

  8. Granja PL, Pouységu L, Deffieux D, Daudé G, De Jéso B, Labrugère C, et al. Cellulose phosphates as biomaterials. II. Surface chemical modification of regenerated cellulose hydrogels. J Appl Polym Sci. 2001;82(13):3354–65. doi:10.1002/app.2194.

    Article  Google Scholar 

  9. Fricain JC, Granja PL, Barbosa MA, de Jéso B, Barthe N, Baquey C. Cellulose phosphates as biomaterials. In vivo biocompatibility studies. Biomaterials. 2002;23(4):971–80. doi:10.1016/s0142-9612(01)00152-1.

    Article  Google Scholar 

  10. Granja PL, Barbosa MA, Pouységu L, De Jéso B, Rouais F, Baquey C. Cellulose phosphates as biomaterials. Mineralization of chemically modified regenerated cellulose hydrogels. J Mater Sci. 2001;36(9):2163–72. doi:10.1023/a:1017587815583.

    Article  Google Scholar 

  11. Granja PL, Ribeiro CC, De Jeso B, Baquey C, Barbosa MA. Mineralization of regenerated cellulose hydrogels. J Mater Sci Mater Med. 2001;12(9):785–91.

    Article  Google Scholar 

  12. Mucalo MR, Kato K, Yokogawa Y. Phosphorylated, cellulose-based substrates as potential adsorbents for bone morphogenetic proteins in biomedical applications: a protein adsorption screening study using cytochrome C as a bone morphogenetic protein mimic. Colloids Surf B. 2009;71(1):52–8. doi:10.1016/j.colsurfb.2009.01.004.

    Article  Google Scholar 

  13. Kim SS, Jeong WY, Shin BC, Oh SY, Kim HW, Rhee JM. Behavior of CHO cells on phosphated cellulose membranes. J Biomed Mater Res. 1998;40(3):401–6.

    Article  Google Scholar 

  14. Nifant’ev EE. The Phosphorylation of Cellulose. Russ Chem Rev. 1965;34(12):942–9. doi:10.1070/RC1965v034n12ABEH001577.

    Article  Google Scholar 

  15. McCormick CL, Callais PA, Hutchinson BH. Solution studies of cellulose in lithium chloride and N,N-dimethylacetamide. Macromolecules. 1985;18(12):2394–401. doi:10.1021/ma00154a010.

    Article  Google Scholar 

  16. Ramos LA, Assaf JM, El Seoud OA, Frollini E. Influence of the supramolecular structure and physicochemical properties of cellulose on its dissolution in a lithium chloride/N,N-Dimethylacetamide solvent system. Biomacromolecules. 2005;6(5):2638–47. doi:10.1021/bm0400776.

    Article  Google Scholar 

  17. Isogai A, Atalla RH. Dissolution of cellulose in aqueous NaOH solutions. Cellulose. 1998;5(4):309–19. doi:10.1023/a:1009272632367.

    Article  Google Scholar 

  18. Petreuş O, Bubulac T, Petreuş I, Cazacu G. Reactions of some phosphorus compounds with cellulose dissolved in aqueous alkaline solution. J Appl Polym Sci. 2003;90(2):327–33. doi:10.1002/app.12532.

    Article  Google Scholar 

  19. Inagaki N, Nakamura S, Asai H, Katsuura K. Phosphorylation of cellulose with phosphorous acid and thermal degradation of the product. J Appl Polym Sci. 1976;20(10):2829–36. doi:10.1002/app.1976.070201017.

    Article  Google Scholar 

  20. Gospodinova N, Grelard A, Jeannin M, Chitanu GC, Carpov A, Thiery V, et al. Efficient solvent-free microwave phosphorylation of microcrystalline cellulose. Green Chem. 2002;4(3):220–2.

    Article  Google Scholar 

  21. Inagaki N, Katsuura K. Modification of cellulose phosphonate with N, N-dimethylacrylamide and 4-vinylpyridine, and flame-retardant properties of the products. J Polym Sci. 1978;16(11):2771–9. doi:10.1002/pol.1978.170161105.

    Google Scholar 

  22. Luneva N, Petrovskaya L, Ezovitova T. Synthesis and properties of cellulose phosphates. Russ J Appl Chem. 2007;80(11):1923–7. doi:10.1134/s1070427207110298.

    Article  Google Scholar 

  23. Weil ED, Levchik SV. Flame retardants for plastics and textiles: practical applications. Cincinnati: Hanser; 2009.

    Book  Google Scholar 

  24. Suflet DM, Chitanu GC, Popa VI. Phosphorylation of polysaccharides: new results on synthesis and characterisation of phosphorylated cellulose. React Funct Polym. 2006;66(11):1240–9. doi:10.1016/j.reactfunctpolym.2006.03.006.

    Article  Google Scholar 

  25. Granja PL, Jéso BD, Bareille R, Rouais F, Baquey C, Barbosa MA. Cellulose phosphates as biomaterials. In vitro biocompatibility studies. React Funct Polym. 2006;66(7):728–39. doi:10.1016/j.reactfunctpolym.2005.10.027.

    Article  Google Scholar 

  26. Petreuş O, Cazacu G, Vasile C, Bubulac T. Noi metode de sinteză a celulozei fosforilate şi utilizarea sa ca biomaterial. Celuloză şi Hârtie. 2003;52(20):20–6.

    Google Scholar 

  27. Simionescu C, Butnaru R, Rozmarin G. Investigation the field of the supermolecular structure of cellulose. Cellulose Chem Technol. 1973;7:153–69.

    Google Scholar 

  28. Pimentel GC, Sederholm CH. Correlation of infrared stretching frequencies and hydrogen bond distances in crystals. J Chem Phys. 1956;24(4):639. doi:10.1063/1.1742588.

    Article  Google Scholar 

  29. Rozmarin G, Simionescu C, Bulacovschi V, Butnaru R. Chimia lemnului si a celulozei. Iasi: Litografia Institutului Politehnic; 1973. p. 175–93.

    Google Scholar 

  30. Merz W. Eine mikroanalytische schnellmethode zur bestimmung von phosphor sowie zur gleichzeitigen bestimmung von phosphor und halogen in organischen substanzen. Microchim Acta. 1959;47(3):456–65. doi:10.1007/bf01216866.

    Article  Google Scholar 

  31. Mosmann T. Rapid colorimetric assay for cellular growth and survival: application to proliferation and cytotoxicity assays. J Immunol Methods. 1983;65(1–2):55–63. doi:10.1016/0022-1759(83)90303-4.

    Article  Google Scholar 

  32. Cory AH, Owen TC, Barltrop JA, Cory JG. Use of an aqueous soluble tetrazolium/formazan assay for cell growth assays in culture. Cancer Commun. 1991;3(7):207–12.

    Google Scholar 

  33. Suzuki M, Yoshida T, Koyama T, Kobayashi S, Kimura M, Hanabusa K, et al. Ionic conduction in partially phosphorylated poly(vinyl alcohol) as polymer electrolytes. Polymer. 2000;41(12):4531–6. doi:10.1016/s0032-3861(99)00682-5.

    Article  Google Scholar 

  34. Granja P, Pouysegu L, Petraud M, De Jeso B, Baquey C, Barbosa M. Cellulose phosphates as biomaterials. I. Synthesis and characterization of highly phosphorylated cellulose gels. J Appl Polym Sci. 2001;82(13):3341–53.

    Article  Google Scholar 

  35. Curtis A, Forrester J, Clark P. Substrate hydroxylation and cell adhesion. J Cell Sci. 1986;86(1):9–24.

    Google Scholar 

  36. Kim S, Jeong W, Shin B, Oh S, Kim H, Rhee J. Behavior of CHO cells on phosphated cellulose membranes. J Biomed Mater Res. 1998;40(3):401–6.

    Article  Google Scholar 

  37. Popescu C, Tibirna C, Raschip I, Popescu M, Ander P, Vasile C. Bulk and surface characterization of unbleached and bleaced softwood kraft pulp fibers. Cellulose Chem Technol. 2008;42(9–10):525–7.

    Google Scholar 

  38. Bismarck A, Kumru ME, Springer J. Characterization of several polymer surfaces by streaming potential and wetting measurements: some reflections on acid–base interactions. J Colloid Interface Sci. 1999;217(2):377–87. doi:10.1006/jcis 1999.6345.

    Article  Google Scholar 

  39. Yamane C, Aoyagi T, Ago M, Sato K, Okajima K, Takahashi T. Two different surface properties of regenerated cellulose due to structural anisotropy. Polymer. 2006;38(8):819–26.

    Article  Google Scholar 

  40. De Bartolo L, Morelli S, Bader A, Drioli E. Evaluation of cell behaviour related to physico-chemical properties of polymeric membranes to be used in bioartificial organs. Biomaterials. 2002;23(12):2485–97. doi:10.1016/s0142-9612(01)00383-0.

    Article  Google Scholar 

  41. Gunnars S, Wågberg L. Cohen stuart MA. model films of cellulose:I. Method development and initial results. Cellulose. 2002;9(3):239–49. doi:10.1023/a:1021196914398.

    Article  Google Scholar 

  42. Kolovith L, Ingall E, Benner R. Composition and cycling of marine organic phosphorus. Limnol Oceanogr. 2001;46(2):309–20.

    Article  Google Scholar 

  43. Maciel GE, Kolodziejski WL, Bertran MS, Dale BE. Carbon-13 NMR and order in cellulose. Macromolecules. 1982;15(2):686–7. doi:10.1021/ma00230a097.

    Article  Google Scholar 

  44. Segal L, Creely JJ, Martin AE, Conrad CM. An empirical method for estimating the degree of crystallinity of native cellulose using the X-ray diffractometer. Text Res J. 1959;29(10):786–94. doi:10.1177/004051755902901003.

    Article  Google Scholar 

  45. Rathna GV. Gelatin hydrogels: enhanced biocompatibility, drug release and cell viability. J Mater Sci Mater Med. 2008;19(6):2351–8. doi:10.1007/s10856-007-3334-9.

    Article  Google Scholar 

Download references

Acknowledgments

This paper was supported by the Research Grant IDEI 2560/2008.

Author information

Authors and Affiliations

  1. Gr.T.Popa University of Medicine and Pharmacy Iasi, 16 Universitatii Str., 700115, Iasi, Romania

    Tudor Petreus, Bogdan Alexandru Stoica, Ancuta Goriuc & Carmen-Elena Cotrutz

  2. Petru Poni Institute of Macromolecular Chemistry, 41A Alley Grigore Ghica Voda, 700487, Iasi, Romania

    Oana Petreus

  3. University “POLITEHNICA” Bucharest, 313 Splai Independentei, Sect. 6, 06004216, Bucharest, Romania

    Iulian-Vasile Antoniac

  4. Babes Bolyai University Cluj-Napoca, 1 Mihail Kogalniceanu Str., 400084, Cluj-Napoca, Romania

    Lucian Barbu-Tudoran

Authors
  1. Tudor Petreus
    View author publications

    You can also search for this author in PubMed Google Scholar

  2. Bogdan Alexandru Stoica
    View author publications

    You can also search for this author in PubMed Google Scholar

  3. Oana Petreus
    View author publications

    You can also search for this author in PubMed Google Scholar

  4. Ancuta Goriuc
    View author publications

    You can also search for this author in PubMed Google Scholar

  5. Carmen-Elena Cotrutz
    View author publications

    You can also search for this author in PubMed Google Scholar

  6. Iulian-Vasile Antoniac
    View author publications

    You can also search for this author in PubMed Google Scholar

  7. Lucian Barbu-Tudoran
    View author publications

    You can also search for this author in PubMed Google Scholar

Corresponding author

Correspondence to Oana Petreus.

Rights and permissions

Reprints and permissions

About this article

Cite this article

Petreus, T., Stoica, B.A., Petreus, O. et al. Preparation and cytocompatibility evaluation for hydrosoluble phosphorous acid-derivatized cellulose as tissue engineering scaffold material. J Mater Sci: Mater Med 25, 1115–1127 (2014). https://doi.org/10.1007/s10856-014-5146-z

Download citation

  • Received:

  • Accepted:

  • Published:

  • Issue Date:

  • DOI: https://doi.org/10.1007/s10856-014-5146-z

Keywords

Search

Navigation