CardioVascular and Interventional Radiology

, Volume 40, Issue 4, pp 576–584 | Cite as

Chitosan–Sodium Tetradecyl Sulfate Hydrogel: Characterization and Preclinical Evaluation of a Novel Sclerosing Embolizing Agent for the Treatment of Endoleaks

  • Fatemeh Zehtabi
  • Vincent Dumont-Mackay
  • Ahmed Fatimi
  • Antony Bertrand-Grenier
  • Hélène Héon
  • Gilles Soulez
  • Sophie LerougeEmail author
Laboratory Investigation



To compare the efficacy of an embolization agent with sclerosing properties (made of chitosan and sodium tetradecyl sulfate, CH–STS) with a similar embolization agent but without sclerosing properties (made of chitosan, CH) in treating endoleaks in a canine endovascular aneurysm repair model.


Two chitosan-based radiopaque hydrogels were prepared, one with STS and one without STS. Their rheological, injectability, and embolizing properties were assessed in vitro; afterwards, their efficacy in occluding endoleaks was compared in a canine bilateral aneurysm model reproducing type I endoleaks (n = 9 each). The primary endpoint was endoleak persistence at 3 or 6 months, assessed on a CT scan and macroscopic examination. Secondary endpoints were the occurrence of stent-graft (SG) thrombosis, the evolution of the aneurysm mean diameter, as well as aneurysm healing and inflammation scores in pathology examinations.


In vitro experiments showed that both products gelled rapidly and presented initial storage moduli greater than 800 Pa, which increased with time. Both gels were compatible with microcatheter injection and occlude flow up to physiological pressure in vitro. In a type I endoleak model, the injection of CH–STS sclerosing gel tended to reduce the risk of occurrence of endoleaks, compared to CH non-sclerosing agent (2/9 vs. 6/9, p = 0.069). No case of SG thrombosis was observed. Moderate inflammation was found around both gels, with a comparable intensity score in both CH and CH–STS groups (2.6 ± 0.9 and 2.7 ± 0.9, respectively; p = 0.789).


Flow occlusion combined with chemical endothelial denudation appears promising for the treatment of endoleaks.

Level of Evidence



Sclerosing agent Endovascular aneurysm repair Chitosan Hydrogels Endoleak Embolization 



This work was supported by the Canadian Institutes of Health Research (PPP-106794) and the Canada Research Chair (S.L). Gilles Soulez is supported by a National Researcher Award from the Fonds de la Recherche en Santé du Quebec. The authors thank Dr. Philippe Roméo for his invaluable help and supervision during the histopathological analysis, Martin Ladouceur for statistical analysis, and Jocelyne Lavoie, Michel Gouin, Elias Assaad, and the animal care staff for their technical help during animal experiments.

Compliance with Ethical Standards

Conflict of interest

Fatemeh Zehtabi, Vincent Dumont-Mackay, Antony Bertrand-Grenier, and Hélène Héon have no commercial, proprietary, or financial interest in any products or companies described in this article (No potential conflict of interest). Ahmed Fatimi, Gilles Soulez, and Sophie Lerouge are co-inventors on a patent pertaining to chitosan–STS gel and have transferred their rights to their institutions. The technology has been exclusively licensed to Cook Medical. Currently, there is a research contract agreement in place between the academic institutions and Cook Medical to develop the technology.

Ethical Approval

All surgeries and interventions were performed under general anesthesia according to the guidelines of the Canadian Council on Animal Care, and were approved by the institutional animal committee.

Supplementary material

270_2016_1557_MOESM1_ESM.docx (1.2 mb)
Supplementary material 1 (DOCX 1277 kb)


  1. 1.
    Nevala T, Biancari F, Manninen H, Aho P-S, Matsi P, Mäkinen K, et al. Type II endoleak after endovascular repair of abdominal aortic aneurysm: effectiveness of embolization. Cardiovasc Interv Radiol. 2010;33(2):278–84. doi: 10.1007/s00270-009-9685-5.CrossRefGoogle Scholar
  2. 2.
    Hiramoto JS, Reilly LM, Schneider DB, Sivamurthy N, Rapp JH, Chuter TAM. Long-term outcome and reintervention after endovascular abdominal aortic aneurysm repair using the Zenith stent graft. J Vasc Surg. 2007;45(3):461–6. doi: 10.1016/j.jvs.2006.11.034.CrossRefPubMedGoogle Scholar
  3. 3.
    Seriki DM, Ashleigh RJ, Butterfield JS, England A, McCollum CN, Akhtar N, et al. Midterm follow-up of a single-center experience of endovascular repair of abdominal aortic aneurysms with use of the Talent stent-graft. J Vasc Interv Radiol. 2006;17(6):973–7. doi: 10.1097/01.RVI.0000222661.64390.3e.CrossRefPubMedGoogle Scholar
  4. 4.
    Chung R, Morgan RA. Type 2 endoleaks post-EVAR: current evidence for rupture risk, intervention and outcomes of treatment. Cardiovasc Interv Radiol. 2015;38(3):507–22. doi: 10.1007/s00270-014-0987-x.CrossRefGoogle Scholar
  5. 5.
    Brewster DC, Jones JE, Chung TK, Lamuraglia GM, Kwolek CJ, Watkins MT, et al. Long-term outcomes after endovascular abdominal aortic aneurysm repair: the first decade. Ann Surg. 2006;244(3):426–38. doi: 10.1097/01.sla.0000234893.88045.dc.PubMedPubMedCentralGoogle Scholar
  6. 6.
    Khaja MS, Park AW, Swee W, Evans AJ, Fritz Angle J, Turba UC, et al. Treatment of type II endoleak using Onyx with long-term imaging follow-up. Cardiovasc Interv Radiol. 2014;37(3):613–22. doi: 10.1007/s00270-013-0706-z.CrossRefGoogle Scholar
  7. 7.
    Muller-Wille R, Wohlgemuth WA, Heiss P, Wiggermann P, Guntner O, Schreyer AG, et al. Transarterial embolization of type II endoleaks after EVAR: the role of ethylene vinyl alcohol copolymer (Onyx). Cardiovasc Interv Radiol. 2013;36(5):1288–95. doi: 10.1007/s00270-013-0567-5.CrossRefGoogle Scholar
  8. 8.
    Sarac TP, Gibbons C, Vargas L, Liu J, Srivastava S, Bena J, et al. Long-term follow-up of type II endoleak embolization reveals the need for close surveillance. J Vasc Surg. 2012;55(1):33–40. doi: 10.1016/j.jvs.2011.07.092.CrossRefPubMedGoogle Scholar
  9. 9.
    Stavropoulos SW, Kim H, Clark TW, Fairman RM, Velazquez O, Carpenter JP. Embolization of type 2 endoleaks after endovascular repair of abdominal aortic aneurysms with use of cyanoacrylate with or without coils. J Vasc Interv Radiol. 2005;16(6):857–61. doi: 10.1097/01.rvi.0000156495.66062.62.CrossRefPubMedGoogle Scholar
  10. 10.
    Martin ML, Dolmatch BL, Fry PD, Machan LS. Treatment of type II endoleaks with Onyx. J Vasc Interv Radiol. 2001;12(5):629–32. doi: 10.1016/S1051-0443(07)61489-4.CrossRefPubMedGoogle Scholar
  11. 11.
    Cao P, De Rango P, Verzini F, Parlani G. Endoleak after endovascular aortic repair: classification, diagnosis and management following endovascular thoracic and abdominal aortic repair. J Cardiovasc Surg. 2010;51(1):53.Google Scholar
  12. 12.
    Ghouri M, Krajcer Z. Endoluminal abdominal aortic aneurysm repair: the latest advances in prevention of distal endograft migration and type 1 endoleak. Tex Heart Inst J. 2010;37(1):19.PubMedPubMedCentralGoogle Scholar
  13. 13.
    Chun JY, Morgan R. Transcatheter embolisation of type 1 endoleaks after endovascular aortic aneurysm repair with Onyx: when no other treatment option is feasible. Eur J Vasc Endovasc Surg. 2013;45(2):141–4. doi: 10.1016/j.ejvs.2012.11.010.CrossRefPubMedGoogle Scholar
  14. 14.
    Eberhardt KM, Sadeghi-Azandaryani M, Worlicek S, Koeppel T, Reiser MF, Treitl M. Treatment of type I endoleaks using transcatheter embolization with Onyx. J Endovasc Ther. 2014;21(1):162–71. doi: 10.1583/13-4349mr2.1.CrossRefPubMedGoogle Scholar
  15. 15.
    Henrikson O, Roos H, Falkenberg M. Ethylene vinyl alcohol copolymer (Onyx) to seal type 1 endoleak. A new technique. Vascular. 2011;19(2):77–81. doi: 10.1258/vasc.2010.oa0257.CrossRefPubMedGoogle Scholar
  16. 16.
    Soulez G, Lerouge S, Darsaut T, Salazkin I, Oliva VL, Raymond J. Role of the endothelial lining in endoleak formation and persistence after endovascular repair of aneurysm. J Vasc Interv Radiol. 2008;19(7):1070–8. doi: 10.1016/j.jvir.2008.04.008.CrossRefPubMedGoogle Scholar
  17. 17.
    Fatimi A, Chabrot P, Berrahmoune S, Coutu JM, Soulez G, Lerouge S. A new injectable radiopaque chitosan-based sclerosing embolizing hydrogel for endovascular therapies. Acta Biomater. 2012;8(7):2712–21. doi: 10.1016/j.actbio.2012.04.006.CrossRefPubMedGoogle Scholar
  18. 18.
    Cabrera J, Cabrera J Jr, Garcia-Olmedo MA, Redondo P. Treatment of venous malformations with sclerosant in microfoam form. Arch Dermatol. 2003;139(11):1409–16. doi: 10.1001/archderm.139.11.1409.CrossRefPubMedGoogle Scholar
  19. 19.
    Dubois J, Soulez G, Oliva VL, Berthiaume MJ, Lapierre C, Therasse E. Soft-tissue venous malformations in adult patients: imaging and therapeutic issues. Radiographics. 2001;21(6):1519–31. doi: 10.1148/radiographics.21.6.g01nv031519.CrossRefPubMedGoogle Scholar
  20. 20.
    Ahmadi F, Oveisi Z, Samani SM, Amoozgar Z. Chitosan based hydrogels: characteristics and pharmaceutical applications. Res Pharm Sci. 2015;10(1):1–16.PubMedPubMedCentralGoogle Scholar
  21. 21.
    Fatimi A, Zehtabi F, Lerouge S. Optimization and characterization of injectable chitosan-iodixanol-based hydrogels for the embolization of blood vessels. J Biomed Mater Res B Appl Biomater. 2016;104B(8):1551–1562. doi: 10.1002/jbm.b.33500.CrossRefGoogle Scholar
  22. 22.
    Soulez G, Lerouge S, Salazkin I, Darsaut T, Oliva VL, Raymond J. Type I and collateral flow in experimental aneurysm models treated with stent-grafts. J Vasc Interv Radiol. 2007;18(2):265–72. doi: 10.1016/j.jvir.2006.12.728.CrossRefPubMedGoogle Scholar
  23. 23.
    Lerouge S, Raymond J, Salazkin I, Qin Z, Gaboury L, Cloutier G, et al. Endovascular aortic aneurysm repair with stent-grafts: experimental models can reproduce endoleaks. J Vasc Interv Radiol. 2004;15(9):971–9. doi: 10.1097/01.rvi.0000130816.33038.ed.CrossRefPubMedGoogle Scholar
  24. 24.
    Stavropoulos SW, Clark TWI, Carpenter JP, Fairman RM, Litt H, Velazquez OC, et al. Use of CT angiography to classify endoleaks after endovascular repair of abdominal aortic aneurysms. J Vasc Interv Radiol. 2005;16(5):663–7. doi: 10.1097/01.RVI.0000152386.97448.F1.CrossRefPubMedGoogle Scholar
  25. 25.
    Carter AJ, Aggarwal M, Kopia GA, Tio F, Tsao PS, Kolata R, et al. Long-term effects of polymer-based, slow-release, sirolimus-eluting stents in a porcine coronary model. Cardiovasc Res. 2004;63(4):617–24. doi: 10.1016/j.cardiores.2004.04.029.CrossRefPubMedGoogle Scholar
  26. 26.
    Lerouge S, Bonneviot MC, Salazkin I, Raymond J, Soulez G. Endothelial denudation combined with embolization in the prevention of endoleaks after endovascular aneurysm repair: an animal study. J Endovasc Ther. 2011;18(5):686–96. doi: 10.1583/11-3541.1.CrossRefPubMedGoogle Scholar
  27. 27.
    Hamada J, Kai Y, Morioka M, Kazekawa K, Ishimaru Y, Iwata H, et al. A mixture of ethylene vinyl alcohol copolymer and ethanol yielding a nonadhesive liquid embolic agent to treat cerebral arteriovenous malformations: initial clinical experience. J Neurosurg. 2002;97(4):881–8. doi: 10.3171/jns.2002.97.4.0881.CrossRefPubMedGoogle Scholar
  28. 28.
    Dompmartin A, Blaizot X, Theron J, Hammer F, Chene Y, Labbe D, et al. Radio-opaque ethylcellulose-ethanol is a safe and efficient sclerosing agent for venous malformations. Eur Radiol. 2011;21(12):2647–56. doi: 10.1007/s00330-011-2213-4.CrossRefPubMedGoogle Scholar
  29. 29.
    Nakai M, Ikoma A, Sato M, Sato H, Nishimura Y, Okamura Y. Prophylactic intraoperative embolization of abdominal aortic aneurysm sacs using N-butyl cyanoacrylate/lipiodol/ethanol mixture with proximal neck aortic balloon occlusion during endovascular abdominal aortic repair. J Vasc Interv Radiol. 2016;27(7):954–60. doi: 10.1016/j.jvir.2016.03.037.CrossRefPubMedGoogle Scholar
  30. 30.
    Chenite A, Buschmann M, Wang D, Chaput C, Kandani N. Rheological characterisation of thermogelling chitosan/glycerol-phosphate solutions. Carbohydr Polym. 2001;46(1):39–47. doi: 10.1016/S0144-8617(00)00281-2.CrossRefGoogle Scholar
  31. 31.
    Coutu JM, Fatimi A, Berrahmoune S, Soulez G, Lerouge S. A new radiopaque embolizing agent for the treatment of endoleaks after endovascular repair: influence of contrast agent on chitosan thermogel properties. J Biomed Mater Res B Appl Biomater. 2013;101(1):153–61. doi: 10.1002/jbm.b.32828.CrossRefPubMedGoogle Scholar
  32. 32.
    Saeed Kilani M, Izaaryene J, Cohen F, Varoquaux A, Gaubert JY, Louis G, et al. Ethylene vinyl alcohol copolymer (Onyx(R)) in peripheral interventional radiology: indications, advantages and limitations. Diagn Interv Imaging. 2015;96(4):319–26. doi: 10.1016/j.diii.2014.11.030.CrossRefPubMedGoogle Scholar
  33. 33.
    Ganji F, Abdekhodaie MJ, Ramazani SAA. Gelation time and degradation rate of chitosan-based injectable hydrogel. J Sol Gel Sci Technol. 2007;42(1):47–53. doi: 10.1007/s10971-006-9007-1.CrossRefGoogle Scholar
  34. 34.
    Adolph R, Vorp DA, Steed DL, Webster MW, Kameneva MV, Watkins SC. Cellular content and permeability of intraluminal thrombus in abdominal aortic aneurysm. J Vasc Surg. 1997;25(5):916–26. doi: 10.1016/S0741-5214(97)70223-4.CrossRefPubMedGoogle Scholar

Copyright information

© Springer Science+Business Media New York and the Cardiovascular and Interventional Radiological Society of Europe (CIRSE) 2017

Authors and Affiliations

  1. 1.Department of Mechanical EngineeringÉcole de technologie supérieureMontrealCanada
  2. 2.Research CentreCentre Hospitalier de l’Université de Montréal (CRCHUM)MontrealCanada
  3. 3.Département de pathologieCentre hospitalier de l’Université de MontréalMontrealCanada
  4. 4.Department of RadiologyUniversité de MontréalMontrealCanada
  5. 5.Faculté Polydisciplinaire, Department of ChemistryUniversité Sultan Moulay SlimaneBeni-MellalMorocco

Personalised recommendations