Skip to main content

Advertisement

Log in

Cell Adhesion and Proliferation on Sulfonated and Non-Modified Chitosan Films

  • Research Article
  • Theme: Recent Trends in the Development of Chitosan-Based Drug Delivery Systems
  • Published:
AAPS PharmSciTech Aims and scope Submit manuscript

Abstract

Three types of chitosan-based films have been prepared and evaluated: a non-modified chitosan film bearing cationizable aliphatic amines and two films made of N-sulfopropyl chitosan derivatives bearing both aliphatic amines and negative sulfonate groups at different ratios. Cell adhesion and proliferation on chitosan films of C2C12 pre-myoblastic cells and B16 cells as tumoral model have been tested. A differential cell behavior has been observed on chitosan films due to their different surface modification. B16 cells have shown lower vinculin expression when cultured on sulfonated chitosan films. This study shows how the interaction among cells and material surface can be modulated by physicochemical characteristics of the biomaterial surface, altering tumoral cell adhesion and proliferation processes.

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.

Fig. 1
Fig. 2
Fig. 3
Fig. 4
Fig. 5
Fig. 6
Fig. 7

Similar content being viewed by others

References

  1. Roberts G. Chitin chemistry. London: Macmillan; 1998.

    Google Scholar 

  2. Aranaz I, Mengíbar M, Harris R, Miralles B, Acosta N, Calderón L, et al. Curr Chem Biol. 2014;1:27–42.

    Article  Google Scholar 

  3. Abarrategi A, Civantos A, Ramos V, Sanz Casado JV, López-Lacomba JL. Biomacromolecules. 2008;9:711–8.

    Article  CAS  PubMed  Google Scholar 

  4. Abarrategi A, García-Cantalejo J, Moreno-Vicente C, Civantos A, Ramos V, Casado JV. Acta Biomater. 2009;5:2633–46.

    Article  CAS  PubMed  Google Scholar 

  5. Busilacchi A, Gigante A, Mattioli-Belmonte M, Manzotti S, Muzzarelli RAA. Chitosan stabilizes platelet growth factors and modulates stem cell differentiation toward tissue regeneration. Carbohydr Polym. 2013;98:665–76.

    Article  CAS  PubMed  Google Scholar 

  6. Jana S, Maji N, Nayak AK, Sen KK, Basu SK. Development of chitosan-based nanoparticles through inter-polymeric complexation for oral drug delivery. Carbohydr Polym. 2013;98:870–6.

    Article  CAS  PubMed  Google Scholar 

  7. Muzzarelli RAA. Chitins and chitosans for the repair of wounded skin, nerve, cartilage and bone. Carbohydr Polym. 2009;76:167–82.

    Article  CAS  Google Scholar 

  8. Muzzarelli RAA. Chitosan composites with inorganics, morphogenetic proteins and stem cells, for bone regeneration. Carbohydr Polym. 2011;83:1433–45.

    Article  CAS  Google Scholar 

  9. Rodrigues S, Dionísio M, Remuñán López C, Grenha A. Biocompatibility of chitosan carriers with application in drug delivery. J Funct Biomater. 2012;3:615–41.

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  10. Guzmán R, Nardecchia S, Gutiérrez MC, Ferrer ML, Ramos V, del Monte F, et al. Chitosan scaffolds containing calcium phosphate salts and rhBMP-2: in vitro and in vivo testing for bone tissue regeneration. PLoS ONE. 2014;9, e87149. doi:10.1371/journal.pone.0087149.

    Article  PubMed  PubMed Central  Google Scholar 

  11. Bhattarai N, Gunn J, Zhang M. Chitosan-based hydrogels for controlled, localized drug delivery. Adv Drug Deliv Rev. 2010;62:83–99.

    Article  CAS  PubMed  Google Scholar 

  12. Freier T, Koh HS, Kazazian K, Shoichet MS. Controlling cell adhesion and degradation of chitosan films by N-acetylation. Biomaterials. 2005;26:5872–8.

    Article  CAS  PubMed  Google Scholar 

  13. Grinnell F. Cellular adhesiveness and extracellular substrata. Int Rev Cytol. 1978;53:65.

    Article  CAS  PubMed  Google Scholar 

  14. Ohgaki M, Kizuki T, Katsura M, Yamashita K. Manipulation of selective cell adhesion and growth by surface charges of electrically polarized hydroxyapatite. J Biomed Mater Res. 2001;57:366–73.

    Article  CAS  PubMed  Google Scholar 

  15. Kleinfeld D, Kahler K, Hockberger P. Controlled outgrowth of dissociated neurons on patterned substrates. J Neurosci. 1988;8:4098–120.

    CAS  PubMed  Google Scholar 

  16. Tan J, Gemeinhart RA, Ma M, Saltzman WM. Improved cell adhesion and proliferation on synthetic phosphonic acid-containing hydrogels. Biomaterials. 2005;26:3663–71.

    Article  CAS  PubMed  Google Scholar 

  17. Aranaz I, Martínez-Campos E, Nash ME, Tardajos MG, Reinecke H, Elvira C, et al. Pseudo-double network hydrogels with unique properties as supports for cell manipulation. J Mater Chem B. 2014;2:3839–48.

    Article  CAS  Google Scholar 

  18. Tsai HS, Wan YZ, Lin JJ, Lie WF. Preparation and properties of sulfopropyl chitosan derivatives with various sulfonation degree. J Appl Polym Sci. 2010;116:1686–93.

    Article  CAS  Google Scholar 

  19. Lavertu M, Xia Z, Serreqi AN, Berrada M, Rodrigues A, et al. A validated 1H NMR method for the determination of the degree of deacetylation of chitosan. J Pharm Biomed Anal. 2003;32:1149–58.

    Article  CAS  PubMed  Google Scholar 

  20. Focher B, Beltranme PL, Naggi A, Torri G. Alkaline N-deacetylation of chitin enhanced by flash treatments: reaction kinetics and structure modifications. Carbohydr Polym. 1990;12:405–18.

    Article  CAS  Google Scholar 

  21. Holme KR, Perlin AS. Chitosan N-sulfate. A water-soluble polyelectrolyte. Carbohydr Res. 1997;302:7–12.

    Article  CAS  PubMed  Google Scholar 

  22. Muzzarelli RAA. Modified chitosans carrying sulfonic acid groups. Carbohydr Polym. 1992;19:231–6.

    Article  CAS  Google Scholar 

  23. Nud’ga LA, Plisko EA, Danilov SN. Synthesis and properties of sulfoethylchitosan. Zhur Prikl Khim. 1974;47:872–5.

    Google Scholar 

  24. Kurita K. Controlled functionalization of the polymer chitin. Prog Polym Sci. 2001;26:1921–71.

    Article  CAS  Google Scholar 

  25. Jerant AF, Johnson JT, Sheridan CD, Caffrey TJ. Early detection and treatment of skin cancer. Am Fam Physician. 2000;62:357–68.

    CAS  PubMed  Google Scholar 

  26. López-Lacomba JL, García-Cantalejo JM, Sanz Casado JV, Abarrategi A, Correas Magaña V. Use of rhBMP-2 activated chitosan films to improve osseointegration. Biomacromolecules. 2006;7:792–8.

    Article  PubMed  Google Scholar 

  27. Friedl P, Wolf K. Tumour-cell invasion and migration: diversity and escape mechanisms. Nat Rev Cancer. 2003;3:362–74.

    Article  CAS  PubMed  Google Scholar 

  28. Szabó A, Merks RM. Cellular potts modeling of tumor growth, tumor invasion, and tumor evolution. Front Oncol. 2013;3:87. doi:10.3389/fonc.2013.00087.

    Article  PubMed  PubMed Central  Google Scholar 

  29. Amaral IF, Cordeiro AL, Sampaio P, Barbosa MA. Attachment, spreading and short-term proliferation of human osteoblastic cells cultured on chitosan films with different degrees of acetylation. J Biomater Sci Polym. 2007;18:469–85.

    Article  CAS  Google Scholar 

  30. Gaggioli C, Sahai E. Melanoma invasion—current knowledge and future directions. Pigment Cell Res. 2007;20:161–72.

    Article  CAS  PubMed  Google Scholar 

  31. Kuphal S, Bauer R, Bosserhoff AK. Integrin signaling in malignant melanoma. Cancer Metastasis Rev. 2005;24:195–222.

    Article  CAS  PubMed  Google Scholar 

  32. Bendas G, Borsig L. Cancer cell adhesion and metastasis: selectins, integrins, and the inhibitory potential of heparins. Int J cell Biol. 2012. doi:10.1155/2012/676731.

    PubMed  PubMed Central  Google Scholar 

  33. Matsuyoshi N, Tanaka T, Toda K, Imamura S. Identification of novel cadherins expressed in human melanoma cells. J Invest Dermatol. 1997;108:908–13.

    Article  CAS  PubMed  Google Scholar 

  34. Bauer R, Hein R, Bosserhoff AK. A secreted form of P-cadherin is expressed in malignant melanoma. Exp Cell Res. 2005;305:418–26.

    Article  CAS  PubMed  Google Scholar 

  35. Bonitsis N, Batistatou A, Karantima S, Charalabopoulos K. The role of cadherin/catenin complex in malignant melanoma. Exp Oncol. 2006;28:187–93.

    CAS  PubMed  Google Scholar 

  36. Liu XP, Zhou ST, Li XY, Chen XC, Zhao X, Qian ZY, et al. Anti-tumor activity of N-trimethyl chitosan encapsulated camptothecin in a mouse melanoma model. J Exp Clin Cancer Res. 2010;29:76. doi:10.1186/1756-9966-29-76.

    Article  PubMed  PubMed Central  Google Scholar 

  37. Mengatto LN, Helbling LN, Luna JA. Recent advances in chitosan films for controlled release of drugs. Recent Pat Drug Deliv Formul. 2012;6:156–70.

    Article  CAS  PubMed  Google Scholar 

  38. Seferian PG, Martinez ML. Immune stimulating activity of two new chitosan containing adjuvant formulation. Vaccine. 2001;19:661–8.

    Article  Google Scholar 

  39. Muzzarelli RAA, Greco F, Busilacchi A, Sollazzo V, Gigante A. Chitosan, hyaluronan and chondroitin sulfate in tissue engineering for cartilage regeneration: a review. Carbohydr Polym. 2012;89:723–39.

    Article  CAS  PubMed  Google Scholar 

  40. Hocker TL, Singh MK, Tsao H. Melanoma genetics and therapeutic approaches in the 21st century: moving from the benchside to the bedside. J Invest Dermatol. 2008;128:2575–95.

    Article  CAS  PubMed  Google Scholar 

Download references

Acknowledgments

This paper was supported by the Spanish Ministry of Economy and Competitiveness (MAT 2010-20001 and CONSOLIDER CSD2009-00088 projects; JAR and IA JAE-PRE fellowship and JAE-DOC contract, respectively), the Spanish Ministry of Science and Innovation (SAF2011-27863 and PET2008_0168), and the Seventh Framework Program of the European Commission (EuroNanomed ERA-NET initiative, REBONE project; PI10/02985FIS). Dr. Carolina Garcia and Dr. Pilar Posada from Characterization Service (Institute of Polymer Science and Technology) are acknowledged for the AFM measurements and support.

Author information

Authors and Affiliations

Authors

Corresponding authors

Correspondence to Enrique Martínez-Campos or Inmaculada Aranaz.

Additional information

Guest Editors: Claudio Salomon, Francisco Goycoolea, and Bruno Moerschbacher

In Memoriam

In loving memory of our Professor José Luis López Lacomba, who taught us everything about science and life.

Enrique Martínez-Campos and Ana Civantos contributed equally to this work.

Electronic supplementary material

Below is the link to the electronic supplementary material.

Figure Suplemental 1

Cell proliferation over S-CS films with different degrees of sulfonation (0,3 and 0,7). A. Cell morphology at 72 h. B. Metabolic activity of C2C12 premioblasts and B16 tumoral cells measured with Alamar Blue, growing on S-CS films (0,3 and 0,7). The results are expressed as Relative Fluorescence Units (RFUs). (GIF 209 kb)

High resolution image (TIF 1291 kb)

Rights and permissions

Reprints and permissions

About this article

Check for updates. Verify currency and authenticity via CrossMark

Cite this article

Martínez-Campos, E., Civantos, A., Redondo, J.A. et al. Cell Adhesion and Proliferation on Sulfonated and Non-Modified Chitosan Films. AAPS PharmSciTech 18, 974–982 (2017). https://doi.org/10.1208/s12249-016-0619-7

Download citation

  • Received:

  • Accepted:

  • Published:

  • Issue Date:

  • DOI: https://doi.org/10.1208/s12249-016-0619-7

KEY WORDS

Navigation