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