Skip to main content

Advertisement

SpringerLink
Log in

Crosstalk between chitosan and cell signaling pathways

  • Review
  • Published:
Cellular and Molecular Life Sciences Aims and scope Submit manuscript

Abstract

The field of tissue engineering (TE) experiences its most exciting time in the current decade. Recent progresses in TE have made it able to translate into clinical applications. To regenerate damaged tissues, TE uses biomaterial scaffolds to prepare a suitable backbone for tissue regeneration. It is well proven that the cell–biomaterial crosstalk impacts tremendously on cell biological activities such as differentiation, proliferation, migration, and others. Clarification of exact biological effects and mechanisms of a certain material on various cell types promises to have a profound impact on clinical applications of TE. Chitosan (CS) is one of the most commonly used biomaterials with many promising characteristics such as biocompatibility, antibacterial activity, biodegradability, and others. In this review, we discuss crosstalk between CS and various cell types to provide a roadmap for more effective applications of this polymer for future uses in tissue engineering and regenerative medicine.

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

(reprinted from Ref. [56] with permission from Wiley InterScience)

Fig. 3

(reprinted from Ref. [82] with permission from Royal Society of Chemistry)

Fig. 4

(reprinted from Ref. [96] with permission from Elsevier B.V.)

Fig. 5

(reprinted from Ref. [182] with permission from Elsevier B.V.)

Fig. 6
Fig. 7

Similar content being viewed by others

References

  1. Gholipourmalekabadi M et al (2015) Optimization of nanofibrous silk fibroin scaffold as a delivery system for bone marrow adherent cells: in vitro and in vivo studies. Biotechnol Appl Biochem 62:785–794

    Article  CAS  PubMed  Google Scholar 

  2. Hamidabadi HG, Shafaroudi MM, Seifi M, Bojnordi MN, Behruzi M, Gholipourmalekabadi M, Shafaroudi AM, Rezaei N (2018) Repair of critical-sized rat calvarial defects with three-dimensional hydroxyapatite-gelatin scaffolds and bone marrow stromal stem cells. Med Arch 72:88

    Article  PubMed  PubMed Central  Google Scholar 

  3. Gholipourmalekabadi M, Sameni M, Radenkovic D, Mozafari M, Mossahebi-Mohammadi M, Seifalian A (2016) Decellularized human amniotic membrane: how viable is it as a delivery system for human adipose tissue-derived stromal cells? Cell Prolif 49:115–121

    Article  CAS  PubMed  Google Scholar 

  4. del Mar Encabo-Berzosa M et al (2017) The effect of PEGylated hollow gold nanoparticles on stem cell migration: potential application in tissue regeneration. Nanoscale 9:9848–9858

    Article  Google Scholar 

  5. Ghasemi Hamidabadi H et al (2017) Chitosan-intercalated montmorillonite/poly (vinyl alcohol) nanofibers as a platform to guide neuronlike differentiation of human dental pulp stem cells. ACS Appl Mater Interfaces 9:11392–11404

    Article  CAS  PubMed  Google Scholar 

  6. Gholipourmalekabadi M, Chauhan NPS, Farhadihosseinabad B, Samadikuchaksaraei A (2016) Human amniotic membrane as a biological source for regenerative medicine. In: Arjmand B (ed) Perinatal tissue-derived stem cells. Springer, New York, pp 81–105

    Chapter  Google Scholar 

  7. Samadikuchaksaraei A, Gholipourmalekabadi M, Farhadihosseinabadi B, Rezvani Z, Mozafari M (2016) Carboxymethyl chitosan/forsterite bone tissue engineering scaffolds: correlations between composition and physico-chemical characteristics. Biointerface Res Appl Chem 6(3)

  8. Delattre C (2017) Current opinion on chitosan and its derivatives: biological impact in antimicrobial applications from nature to chitosan and it derivatives: how it is working? Adv Biotechnol Microbiol 6(2)

  9. Raafat D, Leib N, Wilmes M, François P, Schrenzel J, Sahl H-G (2017) Development of in vitro resistance to chitosan is related to changes in cell envelope structure of Staphylococcus aureus. Carbohydr Polym 157:146–155

    Article  CAS  PubMed  Google Scholar 

  10. Mustafa A, Sîrbu R (2017) Studies on chitosan extraction and its biomedical properties. Eur J Pharm Med Stud 1:7–14

    Google Scholar 

  11. Kim S-K (2010) Chitin, chitosan, oligosaccharides and their derivatives: biological activities and applications. CRC Press, London

    Book  Google Scholar 

  12. Sugier K, Vacherie B, Cornils A, Jamet J-L, Wincker P, Madoui M-A (2017) Chitin distribution in the Oithona digestive and reproductive systems revealed by fluorescence microscopy. PeerJ (preprints)

  13. Leedy MR, Martin HJ, Norowski PA, Jennings JA, Haggard WO, Bumgardner JD (2011) Use of chitosan as a bioactive implant coating for bone-implant applications. In: Chitosan for biomaterials II, pp. 129–165. Springer, New York

  14. Cheung RCF, Ng TB, Wong JH, Chan WY (2015) Chitosan: an update on potential biomedical and pharmaceutical applications. Mar Drugs 13:5156–5186

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  15. Manigandan V, Karthik R, Ramachandran S, Rajagopal S (2018) Chitosan applications in food industry. In: Biopolymers for food design, pp 469–491. Elsevier, New York

  16. Desbrieres J, Guibal E (2018) Chitosan for wastewater treatment. Polym Int 67:7–14

    Article  CAS  Google Scholar 

  17. Song Z, Li G, Guan F, Liu W (2018) Application of chitin/chitosan and their derivatives in the papermaking industry. Polymers 10:389

    Article  CAS  PubMed Central  Google Scholar 

  18. Ding F, Li H, Du Y, Shi X (2018) Recent advances in chitosan-based self-healing materials. Res Chem Intermed 44:1–14

    Article  CAS  Google Scholar 

  19. Silva SS, Mano JF, Reis RL (2017) Ionic liquids in the processing and chemical modification of chitin and chitosan for biomedical applications. Green Chem 19:1208–1220

    Article  CAS  Google Scholar 

  20. Kim S-K, Rajapakse N (2005) Enzymatic production and biological activities of chitosan oligosaccharides (COS): a review. Carbohydr Polym 62:357–368

    Article  CAS  Google Scholar 

  21. Riegger BR, Bäurer B, Mirzayeva A, Tovar GE, Bach M (2018) A systematic approach of chitosan nanoparticle preparation via emulsion crosslinking as potential adsorbent in wastewater treatment. Carbohydr Polym 180:46–54

    Article  CAS  PubMed  Google Scholar 

  22. Meraz OV (2017) Synthesis and characterization of chitosan composites reinforced with carbon nanostructures

  23. Gavhane Y, Gurav A, Yadav A (2013) Chitosan and its applications: a review of literature. Int J Biomed Pharm Sci 4:312–331

    Google Scholar 

  24. Sahoo R, Sahoo S, Nayak PL (2013) Synthesis and characterization of gelatin–chitosan nanocomposite to explore the possible use as drug delivery vehicle. Eur Sci J (ESJ) 9(18)

  25. Park JK, Chung MJ, Choi HN, Park YI (2011) Effects of the molecular weight and the degree of deacetylation of chitosan oligosaccharides on antitumor activity. Int J Mol Sci 12:266–277

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  26. Naqvi S, Moerschbacher BM (2017) The cell factory approach toward biotechnological production of high-value chitosan oligomers and their derivatives: an update. Crit Rev Biotechnol 37:11–25

    Article  CAS  PubMed  Google Scholar 

  27. He X, Li K, Xing R, Liu S, Hu L, Li P (2016) The production of fully deacetylated chitosan by compression method. Egypt J Aquat Res 42:75–81

    Article  Google Scholar 

  28. Wu T (2004). Production and characterization of fungal chitin and chitosan

  29. Wang J, Jiang J-Z, Chen W, Bai Z-W (2016) Data of 1H/13C NMR spectra and degree of substitution for chitosan alkyl urea. Data Brief 7:1228–1236

    Article  PubMed  PubMed Central  Google Scholar 

  30. Nwe N, Furuike T, Tamura H (2009) The mechanical and biological properties of chitosan scaffolds for tissue regeneration templates are significantly enhanced by chitosan from Gongronella butleri. Materials 2:374–398

    Article  CAS  PubMed Central  Google Scholar 

  31. Gholipourmalekabadi M, Zhao S, Harrison BS, Mozafari M, Seifalian AM (2016) Oxygen-generating biomaterials: a new, viable paradigm for tissue engineering? Trends Biotechnol 34:1010–1021

    Article  CAS  PubMed  Google Scholar 

  32. Amaral I, Sampaio P, Barbosa M (2006) Three-dimensional culture of human osteoblastic cells in chitosan sponges: the effect of the degree of acetylation. J Biomed Mater Res Part A 76:335–346

    Article  CAS  Google Scholar 

  33. Chatelet C, Damour O, Domard A (2001) Influence of the degree of acetylation on some biological properties of chitosan films. Biomaterials 22:261–268

    Article  CAS  PubMed  Google Scholar 

  34. Chupa JM, Foster AM, Sumner SR, Madihally SV, Matthew HW (2000) Vascular cell responses to polysaccharide materials: in vitro and in vivo evaluations. Biomaterials 21:2315–2322

    Article  CAS  PubMed  Google Scholar 

  35. Dhiman HK, Ray AR, Panda AK (2004) Characterization and evaluation of chitosan matrix for in vitro growth of MCF-7 breast cancer cell lines. Biomaterials 25:5147–5154

    Article  CAS  PubMed  Google Scholar 

  36. Thein-Han WW, Kitiyanant Y (2007) Chitosan scaffolds for in vitro buffalo embryonic stem-like cell culture: an approach to tissue engineering. J Biomed Mater Res B Appl Biomater 80:92–101

    Article  CAS  PubMed  Google Scholar 

  37. Helander I, Nurmiaho-Lassila E-L, Ahvenainen R, Rhoades J, Roller S (2001) Chitosan disrupts the barrier properties of the outer membrane of Gram-negative bacteria. Int J Food Microbiol 71:235–244

    Article  CAS  PubMed  Google Scholar 

  38. Croisier F, Jérôme C (2013) Chitosan-based biomaterials for tissue engineering. Eur Polym J 49:780–792

    Article  CAS  Google Scholar 

  39. Muzzarelli R (1997) Human enzymatic activities related to the therapeutic administration of chitin derivatives. Cell Mol Life Sci 53:131–140

    Article  CAS  PubMed  Google Scholar 

  40. Tomihata K, Ikada Y (1997) In vitro and in vivo degradation of films of chitin and its deacetylated derivatives. Biomaterials 18:567–575

    Article  CAS  PubMed  Google Scholar 

  41. Prusty A, Gupta BK (2017) Role of chitosan and eudragit in polymer-based extended release matrix tablets—a review. Int J Pharm Sci Res 8:4973–4982

    CAS  Google Scholar 

  42. Li Q, Dunn E, Grandmaison E, Goosen MF (1992) Applications and properties of chitosan. J Bioact Compat Polym 7:370–397

    Article  CAS  Google Scholar 

  43. Singh DK, Ray AR (2000) Biomedical applications of chitin, chitosan, and their derivatives. J Macromol Sci Part C Polym Rev 40:69–83

    Article  Google Scholar 

  44. Schatz C, Viton C, Delair T, Pichot C, Domard A (2003) Typical physicochemical behaviors of chitosan in aqueous solution. Biomacromolecules 4:641–648

    Article  CAS  PubMed  Google Scholar 

  45. Lopez-Leon T, Carvalho EL, Seijo B, Ortega-Vinuesa JL, Bastos-Gonzalez D (2005) Physicochemical characterization of chitosan nanoparticles: electrokinetic and stability behavior. J Colloid Interface Sci 283:344–351

    Article  CAS  PubMed  Google Scholar 

  46. Mazancová P, Némethová V, Treľová D, Kleščíková L, Lacík I, Rázga FJCP (2018) Dissociation of chitosan/tripolyphosphate complexes into separate components upon pH elevation. Polymers 192:104–110

    Google Scholar 

  47. Cruz-Filho AMD, Bordin ARDV, Souza-Flamini LE, Guedes DFDC, Saquy PC, Silva RG, Pécora JDJ (2017) Analysis of the shelf life of chitosan stored in different types of packaging, using colorimetry and dentin microhardness. Restor Dentis Endod 42:87–94

    Article  Google Scholar 

  48. Ali A, Ahmed SJ (2018) A review on chitosan and its nanocomposites in drug delivery. Int J Biol Macromol 109:273–286

    Article  CAS  PubMed  Google Scholar 

  49. Bernkop-Schnürch A, Dünnhaupt SJ (2012) Chitosan-based drug delivery systems. Eur J Pharm Biopharm 81:463–469

    Article  CAS  PubMed  Google Scholar 

  50. Rampino A, Borgogna M, Blasi P, Bellich B, Cesàro AJ (2013) Chitosan nanoparticles: preparation, size evolution and stability. Int J Pharm 455:219–228

    Article  CAS  PubMed  Google Scholar 

  51. Salatin S, Yari Khosroushahi AJ (2017) Overviews on the cellular uptake mechanism of polysaccharide colloidal nanoparticles. J Cell Mol Med 21:1668–1686

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  52. Khalili AA, Ahmad MR (2015) A review of cell adhesion studies for biomedical and biological applications. Int J Mol Sci 16:18149–18184

    Article  CAS  PubMed  Google Scholar 

  53. Bernkop-Schnürch A, Guggi D, Pinter Y (2004) Thiolated chitosans: development and in vitro evaluation of a mucoadhesive, permeation enhancing oral drug delivery system. J Control Release 94:177–186

    Article  CAS  PubMed  Google Scholar 

  54. Bravo-Osuna I, Vauthier C, Farabollini A, Palmieri GF, Ponchel G (2007) Mucoadhesion mechanism of chitosan and thiolated chitosan-poly (isobutyl cyanoacrylate) core-shell nanoparticles. Biomaterials 28:2233–2243

    Article  CAS  PubMed  Google Scholar 

  55. Patel V, Prajapati B, Patel M (2007) Design and characterization of chitosan-containing mucoadhesive buccal patches of propranolol hydrochloride. Acta Pharm 57:61–72

    Article  CAS  PubMed  Google Scholar 

  56. Li Z, Zhang M (2005) Chitosan-alginate as scaffolding material for cartilage tissue engineering. J Biomed Mater Res Part A 75:485–493

    Article  CAS  Google Scholar 

  57. Cui YL, Di Qi A, Liu WG, Wang XH, Wang H, Ma DM, De Yao K (2003) Biomimetic surface modification of poly (l-lactic acid) with chitosan and its effects on articular chondrocytes in vitro. Biomaterials 24:3859–3868

    Article  CAS  PubMed  Google Scholar 

  58. Patrulea V, Ostafe V, Borchard G, Jordan O (2015) Chitosan as a starting material for wound healing applications. Eur J Pharm Biopharm 97:417–426

    Article  CAS  PubMed  Google Scholar 

  59. Gholipourmalekabadi M et al (2018) 3D protein-based bilayer artificial skin for the guided scarless healing of third-degree burn wounds in vivo. Biomacromolecules

  60. Branco A, Saraswathibhatla A, Notbohm J, Thibeault S (2018) Migration and contraction of fibroblasts from normal and scar vocal folds with applications to wound healing. Biophys J 114:517a

    Article  Google Scholar 

  61. Behera SS, Das U, Kumar A, Bissoyi A, Singh AK (2017) Chitosan/TiO2 composite membrane improves proliferation and survival of L929 fibroblast cells: application in wound dressing and skin regeneration. Int J Biol Macromol 98:329–340

    Article  CAS  PubMed  Google Scholar 

  62. Patrulea V, Hirt-Burri N, Jeannerat A, Applegate L, Ostafe V, Jordan O, Borchard G (2016) Peptide-decorated chitosan derivatives enhance fibroblast adhesion and proliferation in wound healing. Carbohydr Polym 142:114–123

    Article  CAS  PubMed  Google Scholar 

  63. Howling GI, Dettmar PW, Goddard PA, Hampson FC, Dornish M, Wood EJ (2001) The effect of chitin and chitosan on the proliferation of human skin fibroblasts and keratinocytes in vitro. Biomaterials 22:2959–2966

    Article  CAS  PubMed  Google Scholar 

  64. Okamoto Y, Watanabe M, Miyatake K, Morimoto M, Shigemasa Y, Minami S (2002) Effects of chitin/chitosan and their oligomers/monomers on migrations of fibroblasts and vascular endothelium. Biomaterials 23:1975–1979

    Article  CAS  PubMed  Google Scholar 

  65. Goy RC, Britto DD, Assis OB (2009) A review of the antimicrobial activity of chitosan. Polímeros 19:241–247

    Article  CAS  Google Scholar 

  66. Li B, Shan C, Ge M, Wang L, Fang Y, Wang Y, Xie G, Sun G (2013) Antibacterial mechanism of chitosan and its applications in protection of plant from bacterial disease: mini review. Asian J Chem 25:10033

    Article  CAS  Google Scholar 

  67. Han Y, Zhao L, Yu Z, Feng J, Yu QJ (2005) Role of mannose receptor in oligochitosan-mediated stimulation of macrophage function. Int Immunopharmacol 5:1533–1542

    Article  CAS  PubMed  Google Scholar 

  68. Otterlei M, Vårum KM, Ryan L, Espevik T (1994) Characterization of binding and TNF-α-inducing ability of chitosans on monocytes: the involvement of CD14. Vaccine 12:825–832

    Article  CAS  PubMed  Google Scholar 

  69. Wu GJ, Tsai GJ (2007) Chitooligosaccharides in combination with interferon-γ increase nitric oxide production via nuclear factor-κB activation in murine RAW264.7 macrophages. Food Chem Toxicol 45:250–258

    Article  CAS  PubMed  Google Scholar 

  70. Bueter CL, Lee CK, Rathinam VA, Healy GJ, Taron CH, Specht CA, Levitz SMJ (2011) Chitosan but not chitin activates the inflammasome by a mechanism dependent upon phagocytosis. J Biol Chem 286:35447–35455

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  71. Yuan Z-X, Zhang Z-R, Zhu D, Sun X, Gong T, Liu J, Luan C-T (2008) Specific renal uptake of randomly 50% N-acetylated low molecular weight chitosan. Mol Pharm 6:305–314

    Article  CAS  Google Scholar 

  72. Huang M, Khor E, Lim LY (2004) Uptake and cytotoxicity of chitosan molecules and nanoparticles: effects of molecular weight and degree of deacetylation. Pharm Res 21:344–353

    Article  CAS  PubMed  Google Scholar 

  73. Behzadi S et al (2017) Cellular uptake of nanoparticles: journey inside the cell. Chem Soc Rev 46:4218–4244

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  74. Jia L, Gao X, Wang Y, Yao N, Zhang X (2014) Structural, phenotypic and functional maturation of bone marrow dendritic cells (BMDCs) induced by chitosan (CTS). Biologicals 42:334–338

    Article  CAS  PubMed  Google Scholar 

  75. Mori A et al (2012) The vaccine adjuvant alum inhibits IL-12 by promoting PI3 kinase signaling while chitosan does not inhibit IL-12 and enhances Th1 and Th17 responses. Eur J Immunol 42:2709–2719

    Article  CAS  PubMed  Google Scholar 

  76. Deog-Yong L, Jeong-Hee H, Han-Sang Y (2002) Chitosan and d-glucosamine induce expression of Th1 cytokine genes in porcine spleen cells. J Vet Med Sci 64:645–648

    Article  Google Scholar 

  77. Wen Z-S, Xu Y-L, Zou X-T, Xu Z-R (2011) Chitosan nanoparticles act as an adjuvant to promote both Th1 and Th2 immune responses induced by ovalbumin in mice. Mar Drugs 9:1038–1055

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  78. Gong Y et al (2015) Chitosan as an adjuvant for a Helicobacter pylori therapeutic vaccine. Mol Med Rep 12:4123–4132

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  79. Feng X et al (2014) 3D porous chitosan scaffolds suit survival and neural differentiation of dental pulp stem cells. Cell Mol Neurobiol 34:859–870

    Article  CAS  PubMed  Google Scholar 

  80. Bof MJ, Bordagaray VC, Locaso DE, García MA (2015) Chitosan molecular weight effect on starch-composite film properties. Food Hydrocolloids 51:281–294

    Article  CAS  Google Scholar 

  81. Dou Y, Sun X, Guo G, Dong J, Lu M, Zhang W (2016). Electrospun pure chitosan nanofibrous mats with high structural stability for dura mater regeneration. Front Bioeng Biotechnol

  82. Kumar PS, Praveen G, Raj M, Chennazhi K, Jayakumar R (2014) Flexible, micro-porous chitosan–gelatin hydrogel/nanofibrin composite bandages for treating burn wounds. RSC Adv 4:65081–65087

    Article  CAS  Google Scholar 

  83. Chakrabarti A, Talukdar D, Pal A, Ray M (2014) Immunomodulation of macrophages by methylglyoxal conjugated with chitosan nanoparticles against Sarcoma-180 tumor in mice. Cell Immunol 287:27–35

    Article  CAS  PubMed  Google Scholar 

  84. Valmikinathan CM, Mukhatyar VJ, Jain A, Karumbaiah L, Dasari M, Bellamkonda RV (2012) Photocrosslinkable chitosan based hydrogels for neural tissue engineering. Soft Matter 8:1964–1976

    Article  CAS  PubMed  Google Scholar 

  85. Park CJ, Gabrielson NP, Pack DW, Jamison RD, Johnson AJW (2009) The effect of chitosan on the migration of neutrophil-like HL60 cells, mediated by IL-8. Biomaterials 30:436–444

    Article  CAS  PubMed  Google Scholar 

  86. Simard P, Galarneau H, Marois S, Rusu D, Hoemann CD, Poubelle PE, El-Gabalawy H, Fernandes MJ (2009) Neutrophils exhibit distinct phenotypes toward chitosans with different degrees of deacetylation: implications for cartilage repair. Arthritis Res Ther 11:R74

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  87. Li H, Shi B, Yan S, Zhao T, Li J, Guo X (2014) Effects of chitosan on the secretion of cytokines and expression of inducible nitric oxide synthase mRNA in peritoneal macrophages of broiler chicken. Braz Arch Biol Technol 57:466–471

    Article  CAS  Google Scholar 

  88. Xia Z, Triffitt JT (2006) A review on macrophage responses to biomaterials. Biomed Mater 1:R1

    Article  CAS  PubMed  Google Scholar 

  89. Da Silva CA, Hartl D, Liu W, Lee CG, Elias JA (2008) TLR-2 and IL-17A in chitin-induced macrophage activation and acute inflammation. J Immunol 181:4279–4286

    Article  PubMed  PubMed Central  Google Scholar 

  90. Zhang P, Liu W, Peng Y, Han B, Yang Y (2014) Toll like receptor 4 (TLR4) mediates the stimulating activities of chitosan oligosaccharide on macrophages. Int Immunopharmacol 23:254–261

    Article  CAS  PubMed  Google Scholar 

  91. Zhu J, Zhang Y, Wu G, Xiao Z, Zhou H, Yu X (2015) Inhibitory effects of oligochitosan on TNF-α, IL-1β and nitric oxide production in lipopolysaccharide-induced RAW264.7 cells. Mol Med Rep 11:729–733

    Article  CAS  PubMed  Google Scholar 

  92. Wernersson S, Pejler G (2014) Mast cell secretory granules: armed for battle. Nat Rev Immunol 14:478–494

    Article  CAS  PubMed  Google Scholar 

  93. Amin K (2012) The role of mast cells in allergic inflammation. Respir Med 106:9–14

    Article  PubMed  Google Scholar 

  94. Vo T-S, Kim J-A, Ngo D-H, Kong C-S, Kim S-K (2012) Protective effect of chitosan oligosaccharides against FcɛRI-mediated RBL-2H3 mast cell activation. Process Biochem 47:327–330

    Article  CAS  Google Scholar 

  95. Farrugia BL, Whitelock JM, Jung M, McGrath B, O’Grady RL, McCarthy SJ, Lord MS (2014) The localisation of inflammatory cells and expression of associated proteoglycans in response to implanted chitosan. Biomaterials 35:1462–1477

    Article  CAS  PubMed  Google Scholar 

  96. Younes I, Frachet V, Rinaudo M, Jellouli K, Nasri M (2016) Cytotoxicity of chitosans with different acetylation degrees and molecular weights on bladder carcinoma cells. Int J Biol Macromol 84:200–207

    Article  CAS  PubMed  Google Scholar 

  97. Zou P, Yang X, Zhang Y, Du P, Yuan S, Yang D, Wang J (2016) Antitumor effects of orally and intraperitoneally administered chitosan oligosaccharides (COSs) on S180-bearing/residual mouse. J Food Sci 81:H3035–H3042

    Article  CAS  PubMed  Google Scholar 

  98. Wimardhani YS, Suniarti DF, Freisleben HJ, Wanandi SI, Siregar NC, Ikeda M-A (2014) Chitosan exerts anticancer activity through induction of apoptosis and cell cycle arrest in oral cancer cells. J Oral Sci 56:119–126

    Article  CAS  PubMed  Google Scholar 

  99. Zhang J, Xia W, Liu P, Cheng Q, Tahi T, Gu W, Li B (2010) Chitosan modification and pharmaceutical/biomedical applications. Mar Drugs 8:1962–1987

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  100. Wiegand C, Winter D, Hipler U-C (2010) Molecular-weight-dependent toxic effects of chitosans on the human keratinocyte cell line HaCaT. Skin Pharmacol Physiol 23:164–170

    Article  CAS  PubMed  Google Scholar 

  101. Senturk S, Mumcuoglu M, Gursoy-Yuzugullu O, Cingoz B, Akcali KC, Ozturk M (2010) Transforming growth factor-beta induces senescence in hepatocellular carcinoma cells and inhibits tumor growth. Hepatology 52:966–974

    Article  CAS  PubMed  Google Scholar 

  102. Mandel A, Larsson P, Sarwar M, Semenas J, Khaja ASS, Persson JL (2018) The interplay between AR, EGF receptor and MMP-9 signaling pathways in invasive prostate cancer. Mol Med 24:34

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  103. Shen K-T, Chen M-H, Chan H-Y, Jeng J-H, Wang Y-J (2009) Inhibitory effects of chitooligosaccharides on tumor growth and metastasis. Food Chem Toxicol 47:1864–1871

    Article  CAS  PubMed  Google Scholar 

  104. Masuda S et al (2014) Anti-tumor properties of orally administered glucosamine and N-acetyl-d-glucosamine oligomers in a mouse model. Carbohydr Polym 111:783–787

    Article  CAS  PubMed  Google Scholar 

  105. Azuma K, Osaki T, Minami S, Okamoto Y (2015) Anticancer and anti-inflammatory properties of chitin and chitosan oligosaccharides. J Funct Biomater 6:33–49

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  106. Chou T-C, Fu E, Wu C-J, Yeh J-H (2003) Chitosan enhances platelet adhesion and aggregation. Biochem Biophys Res Commun 302:480–483

    Article  CAS  PubMed  Google Scholar 

  107. Lord MS, Cheng B, McCarthy SJ, Jung M, Whitelock JM (2011) The modulation of platelet adhesion and activation by chitosan through plasma and extracellular matrix proteins. Biomaterials 32:6655–6662

    Article  CAS  PubMed  Google Scholar 

  108. Shen E-C, Chou TC, Gau CH, Tu HP, Chen YT, Fu E (2006) Releasing growth factors from activated human platelets after chitosan stimulation: a possible bio-material for platelet-rich plasma preparation. Clin Oral Implant Res 17:572–578

    Article  Google Scholar 

  109. Periayah MH, Halim AS, Saad AZM, Yaacob NS, Hussein AR, Karim FA, Rashid AHA, Ujang Z (2015) Chitosan scaffold enhances growth factor release in wound healing in von Willebrand disease. Int J Clin Exp Med 8:15611

    CAS  PubMed  PubMed Central  Google Scholar 

  110. Busilacchi A, Gigante A, Mattioli-Belmonte M, Manzotti S, Muzzarelli RA (2013) Chitosan stabilizes platelet growth factors and modulates stem cell differentiation toward tissue regeneration. Carbohydr Polym 98:665–676

    Article  CAS  PubMed  Google Scholar 

  111. Okamoto Y, Yano R, Miyatake K, Tomohiro I, Shigemasa Y, Minami S (2003) Effects of chitin and chitosan on blood coagulation. Carbohydr Polym 53:337–342

    Article  CAS  Google Scholar 

  112. Hao C, Gao L, Zhang Y, Wang W, Yu G, Guan H, Zhang L, Li C (2015) Acetylated chitosan oligosaccharides act as antagonists against glutamate-induced PC12 cell death via Bcl-2/Bax signal pathway. Mar Drugs 13:1267–1289

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  113. Urquhart DM, Soufan C, Teichtahl AJ, Wluka AE, Hanna F, Cicuttini FM (2008) Factors that may mediate the relationship between physical activity and the risk for developing knee osteoarthritis. Arthritis Res Ther 10:203

    Article  PubMed  PubMed Central  Google Scholar 

  114. Daheshia M, Yao JQ (2008) The interleukin 1β pathway in the pathogenesis of osteoarthritis. J Rheumatol 35:2306–2312

    Article  CAS  PubMed  Google Scholar 

  115. Lin Z, Willers C, Xu J, Zheng M-H (2006) The chondrocyte: biology and clinical application. Tissue Eng 12:1971–1984

    Article  CAS  PubMed  Google Scholar 

  116. Chen Q, Liu S-Q, Du Y-M, Peng H, Sun L-P (2006) Carboxymethyl-chitosan protects rabbit chondrocytes from interleukin-1β-induced apoptosis. Eur J Pharmacol 541:1–8

    Article  CAS  PubMed  Google Scholar 

  117. Zhang C, Yu L, Zhou Y, Zhao Q, Liu S-Q (2016) Chitosan oligosaccharides inhibit IL-1β-induced chondrocyte apoptosis via the P38 MAPK signaling pathway. Glycoconj J 33:735–744

    Article  CAS  PubMed  Google Scholar 

  118. Weinberg BJ, Fermor B, Guilak F (2007) Nitric oxide synthase and cyclooxygenase interactions in cartilage and meniscus. In: Inflammation in the pathogenesis of chronic diseases, pp 31–62. Springer, New York

  119. de Andrés MC, Maneiro E, Martín MA, Arenas J, Blanco FJ (2013) Nitric oxide compounds have different effects profiles on human articular chondrocyte metabolism. Arthritis Res Ther 15:R115

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  120. Zhou PH, Liu SQ, Peng H (2008) The effect of hyaluronic acid on IL-1β-induced chondrocyte apoptosis in a rat model of osteoarthritis. J Orthop Res 26:1643–1648

    Article  CAS  PubMed  Google Scholar 

  121. Menon MB et al (2017) p38 MAPK/MK2-dependent phosphorylation controls cytotoxic RIPK1 signalling in inflammation and infection. Nat Cell Biol 19:1248

    Article  CAS  PubMed  Google Scholar 

  122. Liu C et al (2018) Novel 1, 4-naphthoquinone derivatives induce apoptosis via ROS-mediated p38/MAPK, Akt and STAT3 signaling in human hepatoma Hep3B cells. Int J Biochem Cell Biol 96:9–19

    Article  CAS  PubMed  Google Scholar 

  123. Lu JX, Prudhommeaux F, Meunier A, Sedel L, Guillemin G (1999) Effects of chitosan on rat knee cartilages. Biomaterials 20:1937–1944

    Article  CAS  PubMed  Google Scholar 

  124. Tan ML et al (2014) The potential role of free chitosan in bone trauma and bone cancer management. Biomaterials 35:7828–7838

    Article  CAS  PubMed  Google Scholar 

  125. Shao P, Wei Y, Dass CR, Zhang G, Wu Z (2018) Systemic delivery of free chitosan accelerates femur fracture healing in rats. Curr Drug Targets 19:460–466

    Article  CAS  PubMed  Google Scholar 

  126. Dhivya S, Keshav Narayan A, Logith Kumar R, Viji Chandran S, Vairamani M, Selvamurugan N (2018) Proliferation and differentiation of mesenchymal stem cells on scaffolds containing chitosan, calcium polyphosphate and pigeonite for bone tissue engineering. Cell Prolif 51:e12408

    Article  CAS  Google Scholar 

  127. Bhowmick A, Banerjee SL, Pramanik N, Jana P, Mitra T, Gnanamani A, Das M, Kundu PP (2018) Organically modified clay supported chitosan/hydroxyapatite–zinc oxide nanocomposites with enhanced mechanical and biological properties for the application in bone tissue engineering. Int J Biol Macromol 106:11–19

    Article  CAS  PubMed  Google Scholar 

  128. Qiu J, Liu L, Chen B, Qiao Y, Cao H, Zhu H, Liu X (2018) Graphene oxide as a dual Zn/Mg ion carrier and release platform: enhanced osteogenic activity and antibacterial properties. J Mater Chem B 6:2004–2012

    Article  CAS  Google Scholar 

  129. Rutkovskiy A, Stensløkken K-O, Vaage IJ (2016) Osteoblast differentiation at a glance. Med Sci Monit Basic Res 22:95

    Article  PubMed  PubMed Central  Google Scholar 

  130. Jafary F, Hanachi P, Gorjipour K (2017) Osteoblast differentiation on collagen scaffold with immobilized alkaline phosphatase. Int J Organ Transplant Med 8:195

    CAS  PubMed  PubMed Central  Google Scholar 

  131. Ohara N, Hayashi Y, Yamada S, Kim S-K, Matsunaga T, Yanagiguchi K, Ikeda T (2004) Early gene expression analyzed by cDNA microarray and RT-PCR in osteoblasts cultured with water-soluble and low molecular chitooligosaccharide. Biomaterials 25:1749–1754

    Article  CAS  PubMed  Google Scholar 

  132. Lu Z, Roohani-Esfahani S-I, Li J, Zreiqat H (2015) Synergistic effect of nanomaterials and BMP-2 signalling in inducing osteogenic differentiation of adipose tissue-derived mesenchymal stem cells. Nanomed Nanotechnol Biol Med 11:219–228

    Article  CAS  Google Scholar 

  133. Komori T (2011) Signaling networks in RUNX2-dependent bone development. J Cell Biochem 112:750–755

    Article  CAS  PubMed  Google Scholar 

  134. Hawse JR, Subramaniam M, Ingle JN, Oursler MJ, Rajamannan N, Spelsberg TC (2008) Estrogen-TGFβ cross-talk in bone and other cell types: role of TIEG, Runx2, and other transcription factors. J Cell Biochem 103:383–392

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  135. Wohl GR, Towler DA, Silva MJ (2009) Stress fracture healing: fatigue loading of the rat ulna induces upregulation in expression of osteogenic and angiogenic genes that mimic the intramembranous portion of fracture repair. Bone 44:320–330

    Article  CAS  PubMed  Google Scholar 

  136. Ho WP, Chan WP, Hsieh MS, Chen RM (2009) Runx2-mediated bcl-2 gene expression contributes to nitric oxide protection against hydrogen peroxide-induced osteoblast apoptosis. J Cell Biochem 108:1084–1093

    Article  CAS  PubMed  Google Scholar 

  137. Ho M-H, Liao M-H, Lin Y-L, Lai C-H, Lin P-I, Chen R-M (2014) Improving effects of chitosan nanofiber scaffolds on osteoblast proliferation and maturation. Int J Nanomed 9:4293

    Google Scholar 

  138. Ho M-H, Yao C-J, Liao M-H, Lin P-I, Liu S-H, Chen R-M (2015) Chitosan nanofiber scaffold improves bone healing via stimulating trabecular bone production due to upregulation of the Runx2/osteocalcin/alkaline phosphatase signaling pathway. Int J Nanomed 10:5941

    CAS  Google Scholar 

  139. Mendis E, Kim M-M, Rajapakse N, Kim S-K (2007) An in vitro cellular analysis of the radical scavenging efficacy of chitooligosaccharides. Life Sci 80:2118–2127

    Article  CAS  PubMed  Google Scholar 

  140. Liu H-T, Li W-M, Xu G, Li X-Y, Bai X-F, Wei P, Yu C, Du Y-G (2009) Chitosan oligosaccharides attenuate hydrogen peroxide-induced stress injury in human umbilical vein endothelial cells. Pharmacol Res 59:167–175

    Article  CAS  PubMed  Google Scholar 

  141. Panieri E, Santoro M (2016) ROS homeostasis and metabolism: a dangerous liason in cancer cells. Cell Death Dis 7:e2253

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  142. Khodagholi F, Eftekharzadeh B, Maghsoudi N, Rezaei PF (2010) Chitosan prevents oxidative stress-induced amyloid β formation and cytotoxicity in NT2 neurons: involvement of transcription factors Nrf2 and NF-κB. Mol Cell Biochem 337:39–51

    Article  CAS  PubMed  Google Scholar 

  143. Ryu B, Himaya S, Napitupulu RJ, Eom T-K, Kim S-K (2012) Sulfated chitooligosaccharide II (SCOS II) suppress collagen degradation in TNF-induced chondrosarcoma cells via NF-κB pathway. Carbohydr Res 350:55–61

    Article  CAS  PubMed  Google Scholar 

  144. Wei P, Ma P, Xu Q-S, Bai Q-H, Gu J-G, Xi H, Du Y-G, Yu C (2012) Chitosan oligosaccharides suppress production of nitric oxide in lipopolysaccharide-induced N9 murine microglial cells in vitro. Glycoconj J 29:285–295

    Article  CAS  PubMed  Google Scholar 

  145. Fang I-M, Yang C-H, Yang C-M, Chen M-S (2013) Chitosan oligosaccharides attenuates oxidative-stress related retinal degeneration in rats. PLoS ONE 8:e77323

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  146. Jeng PS, Inoue-Yamauchi A, Hsieh JJ, Cheng EH (2018) BH3-dependent and independent activation of BAX and BAK in mitochondrial apoptosis. Curr Opin Physiol

  147. Fang I-M, Yang C-M, Yang C-H (2015) Chitosan oligosaccharides prevented retinal ischemia and reperfusion injury via reduced oxidative stress and inflammation in rats. Exp Eye Res 130:38–50

    Article  CAS  PubMed  Google Scholar 

  148. Tan K, Wang X, Zhang J, Zhuang Z, Dong T (2018) Effect of chitosan porous scaffolds combined with bone marrow mesenchymal stem cells in repair of neurological deficit after traumatic brain injury in rats. Chinese J Reparative Reconstr Surg (Zhongguo xiufu chongjian waike zazhi) 32:745–752

    Google Scholar 

  149. Moattari M, Kouchesfehani HM, Kaka G, Sadraie SH, Naghdi M, Mansouri K (2018) Chitosan-film associated with mesenchymal stem cells enhanced regeneration of peripheral nerves: a rat sciatic nerve model. J Chem Neuroanat 88:46–54

    Article  CAS  PubMed  Google Scholar 

  150. Damas I, Zuliani C, Moraes A, Westin C, Kharmandayan P, Andrade K, Mamonei R, Coimbra I (2018) Comparision between human amniotic fluid and adipose tissue mesenchymal stem cells induced-chondrogenesis cultured in chitosan-xanthan scaffold stimulated with TGF-β3. Osteoarthr Cartil 26:S298–S299

    Article  Google Scholar 

  151. Wang A, Ao Q, He Q, Gong X, Gong K, Gong Y, Zhao N, Zhang X (2006) Neural stem cell affinity of chitosan and feasibility of chitosan-based porous conduits as scaffolds for nerve tissue engineering. Tsinghua Sci Technol 11:415–420

    Article  CAS  Google Scholar 

  152. Li Z, Tian X, Yuan Y, Song Z, Zhang L, Wang X, Li T (2013) Effect of cell culture using chitosan membranes on stemness marker genes in mesenchymal stem cells. Mol Med Rep 7:1945–1949

    Article  CAS  PubMed  Google Scholar 

  153. Liu HT, Li WM, Li XY, Xu QS, Liu QS, Bai XF, Yu C, Du YG (2010) Chitosan oligosaccharides inhibit the expression of interleukin-6 in lipopolysaccharide-induced human umbilical vein endothelial cells through p38 and ERK1/2 protein kinases. Basic Clin Pharmacol Toxicol 106:362–371

    Article  CAS  PubMed  Google Scholar 

  154. Segers VF, Lee RT (2008) Stem-cell therapy for cardiac disease. Nature 451:937–942

    Article  CAS  PubMed  Google Scholar 

  155. Liu Z et al (2012) The influence of chitosan hydrogel on stem cell engraftment, survival and homing in the ischemic myocardial microenvironment. Biomaterials 33:3093–3106

    Article  CAS  PubMed  Google Scholar 

  156. Yang J, Liu A, Zhou C (2011) Proliferation of mesenchymal stem cell on chitosan films associated with convex micro-topography. J Biomater Sci Polym Ed 22:919–929

    Article  CAS  PubMed  Google Scholar 

  157. Ragetly GR, Griffon DJ, Lee H-B, Fredericks LP, Gordon-Evans W, Chung YS (2010) Effect of chitosan scaffold microstructure on mesenchymal stem cell chondrogenesis. Acta Biomater 6:1430–1436

    Article  CAS  PubMed  Google Scholar 

  158. Van Bockstaele E, Ross J (2018) SI: Catecholamine dysregulation and neurodegenerative disease catecholamine dysregulation in neurodegenerative disease: from molecular mechanisms to circuit dysfunctioned. Elsevier, New York

    Google Scholar 

  159. Sweeney MD, Sagare AP, Zlokovic BV (2018) Blood–brain barrier breakdown in Alzheimer disease and other neurodegenerative disorders. Nat Rev Neurol 14:133

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  160. Hao C, Wang W, Wang S, Zhang L, Guo Y (2017) An overview of the protective effects of chitosan and acetylated chitosan oligosaccharides against neuronal disorders. Mar Drugs 15:89

    Article  CAS  PubMed Central  Google Scholar 

  161. Amor S, Peferoen LA, Vogel DY, Breur M, van der Valk P, Baker D, van Noort JM (2014) Inflammation in neurodegenerative diseases—an update. Immunology 142:151–166

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  162. Kimura Y, Shibuya N, Kimura H (2018) Sulfite protects neurons from oxidative stress. Br J Pharmacol

  163. Im H, Lim J (2018) Oxidative stress caused by accumulation of misfolded Z-type alpha1-antitrypsin. Free Radical Biol Med 120:S71–S72

    Article  Google Scholar 

  164. Chen B, Li J, Borgens RB (2018) Neuroprotection by chitosan nanoparticles in oxidative stress-mediated injury. BMC Res Notes 11:49

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  165. Xu W, Huang H-C, Lin C-J, Jiang Z-F (2010) Chitooligosaccharides protect rat cortical neurons against copper induced damage by attenuating intracellular level of reactive oxygen species. Bioorg Med Chem Lett 20:3084–3088

    Article  CAS  PubMed  Google Scholar 

  166. Atwood CS, Huang X, Moir RD, Tanzi RE, Bush AI (2018) Role of free radicals and metal ions in the pathogenesis of Alzheimer’s disease. In: Metal ions in biological systems, pp 309–364. Routledge, Abingdon

  167. Murphy TH, Miyamoto M, Sastre A, Schnaar RL, Coyle JT (1989) Glutamate toxicity in a neuronal cell line involves inhibition of cystine transport leading to oxidative stress. Neuron 2:1547–1558

    Article  CAS  PubMed  Google Scholar 

  168. Zhou S, Yang Y, Gu X, Ding F (2008) Chitooligosaccharides protect cultured hippocampal neurons against glutamate-induced neurotoxicity. Neurosci Lett 444:270–274

    Article  CAS  PubMed  Google Scholar 

  169. Kim M-S, Sung M-J, Seo S-B, Yoo S-J, Lim W-K, Kim H-M (2002) Water-soluble chitosan inhibits the production of pro-inflammatory cytokine in human astrocytoma cells activated by amyloid β peptide and interleukin-1β. Neurosci Lett 321:105–109

    Article  CAS  PubMed  Google Scholar 

  170. Pangestuti R, Bak S-S, Kim S-K (2011) Attenuation of pro-inflammatory mediators in LPS-stimulated BV2 microglia by chitooligosaccharides via the MAPK signaling pathway. Int J Biol Macromol 49:599–606

    Article  CAS  PubMed  Google Scholar 

  171. Verma DK et al (2018) New therapeutic activity of metabolic enhancer piracetam in treatment of neurodegenerative disease: participation of caspase independent death factors, oxidative stress, inflammatory responses and apoptosis. Biochim Biophys Acta (BBA) Mol Basis Dis 1864:2078–2096

    Article  CAS  Google Scholar 

  172. Wang X, Miao J, Yan C, Ge R, Liang T, Liu E, Li Q (2016) Chitosan attenuates dibutyltin-induced apoptosis in PC12 cells through inhibition of the mitochondria-dependent pathway. Carbohydr Polym 151:996–1005

    Article  CAS  PubMed  Google Scholar 

  173. Koo H-N, Jeong H-J, Hong S-H, Choi J-H, An N-H, Kim H-M (2002) High molecular weight water-soluble chitosan protects against apoptosis induced by serum starvation in human astrocytes. J Nutr Biochem 13:245–249

    Article  CAS  PubMed  Google Scholar 

  174. Green DR, Kroemer G (2009) Cytoplasmic functions of the tumour suppressor p53. Nature 458:1127

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  175. Lim YY et al (2018) Association of β-amyloid and apolipoprotein E ε4 with memory decline in preclinical Alzheimer disease. JAMA Neurol 75:488–494

    Article  PubMed  Google Scholar 

  176. Dai X, Hou W, Sun Y, Gao Z, Zhu S, Jiang Z (2015) Chitosan oligosaccharides inhibit/disaggregate fibrils and attenuate amyloid β-mediated neurotoxicity. Int J Mol Sci 16:10526–10536

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  177. Cao Z, Gilbert RJ, He W (2009) Simple agarose–chitosan gel composite system for enhanced neuronal growth in three dimensions. Biomacromolecules 10:2954–2959

    Article  CAS  PubMed  Google Scholar 

  178. Blanpain C (2007) Epidermal stem cells. Bull Mem Acad R Med Belg 162:418

    CAS  PubMed  Google Scholar 

  179. Chai J, Modak C, Mouazzen W, Narvaez R, Pham J (2010) Epithelial or mesenchymal: where to draw the line? Biosci Trends 4(3)

  180. Paz AC, Soleas J, Poon JC, Trieu D, Waddell TK, McGuigan AP (2013) Challenges and opportunities for tissue-engineering polarized epithelium. Tissue Eng Part B Rev 20:56–72

    Article  PubMed  Google Scholar 

  181. Muanprasat C, Wongkrasant P, Satitsri S, Moonwiriyakit A, Pongkorpsakol P, Mattaveewong T, Pichyangkura R, Chatsudthipong V (2015) Activation of AMPK by chitosan oligosaccharide in intestinal epithelial cells: mechanism of action and potential applications in intestinal disorders. Biochem Pharmacol 96:225–236

    Article  CAS  PubMed  Google Scholar 

  182. Hsiao Y-C, Chen C-N, Chen Y-T, Yang T-L (2013) Controlling branching structure formation of the salivary gland by the degree of chitosan deacetylation. Acta Biomater 9:8214–8223

    Article  CAS  PubMed  Google Scholar 

  183. Yang T-L, Lin L, Hsiao Y-C, Lee H-W, Young T-H (2012) Chitosan biomaterials induce branching morphogenesis in a model of tissue-engineered glandular organs in serum-free conditions. Tissue Eng Part A 18:2220–2230

    Article  CAS  PubMed  Google Scholar 

  184. Patil SV, Nanduri LS (2017) Interaction of chitin/chitosan with salivary and other epithelial cells—an overview. Int J Biol Macromol 104:1398–1406

    Article  CAS  PubMed  Google Scholar 

  185. Huang TW, Wei CK, Su HW, Fang KM (2017) Chitosan promotes aquaporin formation and inhibits mucociliary differentiation of nasal epithelial cells through increased TGF-β1 production. J Tissue Eng Regen Med 11:3567–3575

    Article  CAS  PubMed  Google Scholar 

  186. Smith J, Wood E, Dornish M (2004) Effect of chitosan on epithelial cell tight junctions. Pharm Res 21:43–49

    Article  CAS  PubMed  Google Scholar 

  187. Liu SH, Huang YW, Wu CT, Chiu CY, Chiang MT (2013) Low molecular weight chitosan accelerates glucagon-like peptide-1 secretion in human intestinal endocrine cells via a p38-dependent pathway. J Agric Food Chem 61:4855–4861

    Article  CAS  PubMed  Google Scholar 

  188. Montorfano I et al (2014) Oxidative stress mediates the conversion of endothelial cells into myofibroblasts via a TGF-β1 and TGF-β2-dependent pathway. Lab Investig 94:1068

    Article  CAS  PubMed  Google Scholar 

  189. Förstermann U, Xia N, Li H (2017) Roles of vascular oxidative stress and nitric oxide in the pathogenesis of atherosclerosis. Circ Res 120:713–735

    Article  CAS  PubMed  Google Scholar 

  190. Amiya E (2016) Interaction of hyperlipidemia and reactive oxygen species: insights from the lipid-raft platform. World J Cardiol 8:689

    Article  PubMed  PubMed Central  Google Scholar 

  191. Xu H-B, Huang Z-Q (2007) Icariin enhances endothelial nitric-oxide synthase expression on human endothelial cells in vitro. Vasc Pharmacol 47:18–24

    Article  CAS  Google Scholar 

  192. Nam K-S, Kim M-K, Shon Y-H (2007) Inhibition of proinflammatory cytokine-induced invasiveness of HT-29 cells by chitosan oligosaccharide. J Microbiol Biotechnol 17:2042–2045

    CAS  PubMed  Google Scholar 

  193. Wang Z, Zheng L, Yang S, Niu R, Chu E, Lin X (2007) N-acetylchitooligosaccharide is a potent angiogenic inhibitor both in vivo and in vitro. Biochem Biophys Res Commun 357:26–31

    Article  CAS  PubMed  Google Scholar 

  194. Liu H-T, Huang P, Ma P, Liu Q-S, Yu C, Du Y-G (2011) Chitosan oligosaccharides suppress LPS-induced IL-8 expression in human umbilical vein endothelial cells through blockade of p38 and Akt protein kinases. Acta Pharmacol Sin 32:478–486

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  195. Li Y, Xu Q, Wei P, Cheng L, Peng Q, Li S, Yin H, Du Y (2014) Chitosan oligosaccharides downregulate the expression of E-selectin and ICAM-1 induced by LPS in endothelial cells by inhibiting MAP kinase signaling. Int J Mol Med 33:392–400

    Article  CAS  PubMed  Google Scholar 

  196. Nam K-S, Shon Y-H (2009) Suppression of metastasis of human breast cancer cells by chitosan oligosaccharides. J Microbiol Biotechnol 19:629–633

    Article  CAS  PubMed  Google Scholar 

  197. Huang X, Huang X, Jiang X-H, Hu F-Q, Du Y-Z, Zhu Q-F, Jin C-S (2012) In vitro antitumour activity of stearic acid-g-chitosan oligosaccharide polymeric micelles loading podophyllotoxin. J Microencapsul 29:1–8

    Article  CAS  PubMed  Google Scholar 

  198. Zong A et al (2013) Anti-metastatic and anti-angiogenic activities of sulfated polysaccharide of Sepiella maindroni ink. Carbohydr Polym 91:403–409

    Article  CAS  PubMed  Google Scholar 

  199. Zheng M, Han B, Yang Y, Liu W (2011) Synthesis, characterization and biological safety of O-carboxymethyl chitosan used to treat sarcoma 180 tumor. Carbohydr Polym 86:231–238

    Article  CAS  Google Scholar 

  200. Hu F, Chen W, Zhao M, Yuan H, Du Y (2013) Effective antitumor gene therapy delivered by polyethylenimine-conjugated stearic acid-g-chitosan oligosaccharide micelles. Gene Ther 20:597

    Article  CAS  PubMed  Google Scholar 

  201. Termsarasab U, Cho H-J, Kim DH, Chong S, Chung S-J, Shim C-K, Moon HT, Kim D-D (2013) Chitosan oligosaccharide-arachidic acid-based nanoparticles for anti-cancer drug delivery. Int J Pharm 441:373–380

    Article  CAS  PubMed  Google Scholar 

  202. Li TSC, Yawata T, Honke K (2014) Efficient siRNA delivery and tumor accumulation mediated by ionically cross-linked folic acid-poly (ethylene glycol)-chitosan oligosaccharide lactate nanoparticles: for the potential targeted ovarian cancer gene therapy. Eur J Pharm Sci 52:48–61

    Article  CAS  PubMed  Google Scholar 

  203. Younes I, Hajji S, Frachet V, Rinaudo M, Jellouli K, Nasri M (2014) Chitin extraction from shrimp shell using enzymatic treatment. Antitumor, antioxidant and antimicrobial activities of chitosan. Int J Biol Macromol 69:489–498

    Article  CAS  PubMed  Google Scholar 

  204. Chien R-C, Yen M-T, Mau J-L (2016) Antimicrobial and antitumor activities of chitosan from shiitake stipes, compared to commercial chitosan from crab shells. Carbohydr Polym 138:259–264

    Article  CAS  PubMed  Google Scholar 

  205. Chokradjaroen C, Rujiravanit R, Watthanaphanit A, Theeramunkong S, Saito N, Yamashita K, Arakawa R (2017) Enhanced degradation of chitosan by applying plasma treatment in combination with oxidizing agents for potential use as an anticancer agent. Carbohydr Polym 167:1–11

    Article  CAS  PubMed  Google Scholar 

  206. Srinivasan H, Kanayairam V, Ravichandran R (2018) Chitin and chitosan preparation from shrimp shells Penaeus monodon and its human ovarian cancer cell line, PA-1. Int J Biol Macromol 107:662–667

    Article  CAS  PubMed  Google Scholar 

Download references

Acknowledgements

We would like to show our gratitude to Dr. Saman Mohammadiamanab for his comments on this paper.

Author information

Authors and Affiliations

  1. Department of Biotechnology, School of Advanced Technologies in Medicine, Shahid Beheshti University of Medical Sciences, Tehran, Iran

    Behrouz Farhadihosseinabadi & Mohamad Eftekhary

  2. Department of Medical Nanotechnology, Faculty of Advanced Medical Science, Tabriz University of Medical Science, Tabriz, Iran

    Amir Zarebkohan

  3. Drug Applied Research Center, Tabriz University of Medical Sciences, Tabriz, Iran

    Amir Zarebkohan

  4. Baqiyatallah Research Center for Gastroenterology and Liver Diseases, Baqiyatallah University of Medical Sciences, Tehran, Iran

    Mohammad Heiat

  5. Applied Biotechnology Research Center, Baqiyatallah University of Medical Sciences, Tehran, Iran

    Mehrdad Moosazadeh Moghaddam

  6. Cellular and Molecular Research Centre, Iran University of Medical Sciences, Tehran, Iran

    Mazaher Gholipourmalekabadi

  7. Department of Tissue Engineering & Regenerative Medicine, Faculty of Advanced Technologies in Medicine, Iran University of Medical Sciences, Tehran, Iran

    Mazaher Gholipourmalekabadi

Authors
  1. Behrouz Farhadihosseinabadi
    View author publications

    You can also search for this author in PubMed Google Scholar

  2. Amir Zarebkohan
    View author publications

    You can also search for this author in PubMed Google Scholar

  3. Mohamad Eftekhary
    View author publications

    You can also search for this author in PubMed Google Scholar

  4. Mohammad Heiat
    View author publications

    You can also search for this author in PubMed Google Scholar

  5. Mehrdad Moosazadeh Moghaddam
    View author publications

    You can also search for this author in PubMed Google Scholar

  6. Mazaher Gholipourmalekabadi
    View author publications

    You can also search for this author in PubMed Google Scholar

Corresponding authors

Correspondence to Mehrdad Moosazadeh Moghaddam or Mazaher Gholipourmalekabadi.

Ethics declarations

Conflict of interest

There is no conflict of interest.

Additional information

Publisher's Note

Springer Nature remains neutral with regard to jurisdictional claims in published maps and institutional affiliations.

Rights and permissions

Reprints and permissions

About this article

Check for updates. Verify currency and authenticity via CrossMark

Cite this article

Farhadihosseinabadi, B., Zarebkohan, A., Eftekhary, M. et al. Crosstalk between chitosan and cell signaling pathways. Cell. Mol. Life Sci. 76, 2697–2718 (2019). https://doi.org/10.1007/s00018-019-03107-3

Download citation

  • Received:

  • Revised:

  • Accepted:

  • Published:

  • Issue Date:

  • DOI: https://doi.org/10.1007/s00018-019-03107-3

Keywords

Search

Navigation