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

Zehtabi, Fatemeh; Dumont-Mackay, Vincent; Fatimi, Ahmed; Bertrand-Grenier, Antony; Héon, Hélène; Soulez, Gilles; Lerouge, Sophie

doi:10.1007/s00270-016-1557-1

Cited by 17 publications

(16 citation statements)

References 32 publications

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“…However, probably because of the small sample size, this effect did not reach the statistical significance. The better efficacy of Chi-STS over only Chi gels was previously reported [ 8 ]. SWI could be used to monitor the stiffness and biodegradation of new generation embolisation agents.…”

Section: Discussionsupporting

confidence: 64%

“…Animal procedures were approved by our institution’s Animal Care Committee in accordance with Canadian Council on Animal Care guidelines. The method for the creation of occlusive and sclerosing gels and their safety/efficacy to treat endoleak was previously reported including six animals of the current study [ 8 ]. The current publication focus on the potential of SWI for characterising aneurysm healing after endoleak embolisation.…”

Section: Methodsmentioning

confidence: 99%

“…Embolisation with thrombin, colis, or liquid agent (ethylene vinyl alcohol copolymer, cyanoacrylates) has been proposed to prevent or treat endoleaks [ 7 ]. However, despite embolisation, endoleak recurrences are frequently observed [ 7 , 8 ] and the role of endothelial lining in endoleak formation and recurrence was established [ 9 ]. To improve the results of endoleak embolisation, an injectable chitosan hydrogel combined with a sclerosing agent (sodium tetradecyl sulfate [STS]) was developed to promote endothelial ablation and fibrous healing of the sac [ 8 , 9 ].…”

Section: Introductionmentioning

confidence: 99%

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Shear wave elasticity imaging for residual endoleak and thrombus characterisation after endoleak embolisation following endovascular aneurysm repair: a canine animal study

et al. 2018

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BackgroundTo evaluate residual endoleak and thrombus organisation with shear wave imaging (SWI) after endoleak embolisation through an animal study.MethodsThis prospective experimental study involved eight dogs with creation of 16 iliac aneurysms and type I endoleak after endovascular aneurysm repair (EVAR). Embolisation agents were injected into the sac to seal endoleak. SWI and colour flow Doppler ultrasound (DUS) were performed at implantation, one week, and one and three months after implantation; for three dogs, SWI and DUS were also performed six months after implantation. Digital subtraction angiography and contrast-enhanced computed tomography were performed at sacrifice. Macroscopic and histopathological analyses were processed to identify regions of interest (ROIs) for endoleak, fresh thrombus, organised thrombus and embolisation agent, where SWI elasticity moduli were compared.ResultsAt sacrifice, nine aneurysms had residual endoleak, while seven were sealed. Ten had a fresh and 15 had an organised thrombus. SWI was able to detect all endoleaks, including two cases undetected with DUS. Elasticity moduli of 0.2 kPa ± 0.1 kPa (mean ± SD), 9.5 kPa ± 3.3 kPa, 48.1 kPa ± 21.3 kPa and 44.9 kPa ± 23.7 kPa were found in the ROIs positioned in endoleaks, fresh thrombi, organised thrombi and embolisation agent, respectively. Elasticity values of endoleak and fresh thrombus were lower than those of organised thrombi and embolisation agent (p < 0.001). Stiffness of fresh thrombus at one week (8.7 kPa ± 3.6 kPa) increased at three months (30.2 kPa ± 13.8 kPa), indicating thrombus maturation (p < 0.001).ConclusionsIn a dog model of iliac EVAR, SWI was able to identify endoleak, thrombus maturation and embolising agents after endoleak embolisation.

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Section: Discussionsupporting

confidence: 64%

Section: Methodsmentioning

confidence: 99%

Section: Introductionmentioning

confidence: 99%

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Shear wave elasticity imaging for residual endoleak and thrombus characterisation after endoleak embolisation following endovascular aneurysm repair: a canine animal study

et al. 2018

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“…All angiographic procedures were performed in an experimental angiography room (Artis Q, Siemens, Forchheim, Germany). At the start of the procedure, through femoral approach, the gastroduodenal artery and the left gastric artery (arising in the pig from the proper hepatic artery) were embolized with an experimental gel made of chitosan‐sodium tetradecyl sulfate . Then, a 5‐French compliant occlusion balloon catheter (Fogarty, Edwards Lifescience, Irvine, CA) was introduced in the proximal hepatic artery 3–4 cm below the right–left bifurcation.…”

Section: Methodsmentioning

confidence: 99%

“…At the start of the procedure, through femoral approach, the gastroduodenal artery and the left gastric artery (arising in the pig from the proper hepatic artery) were embolized with an experimental gel made of chitosan-sodium tetradecyl sulfate. 23 Then, a 5-French compliant occlusion balloon catheter (Fogarty, Edwards Lifescience, Irvine, CA) was introduced in the proximal hepatic artery 3-4 cm below the right-left bifurcation. To evaluate the influence of selective liver embolization on the proximal hepatic flow, three pigs had selective particle embolization of the left medial lobe using a microcatheter (FasTracker 325, Boston Scientific, Marlborough, MA) advanced coaxially through the deflated balloon catheter.…”

Section: A In Vivo Flow Modulation and Measurementmentioning

confidence: 99%

Selective embolization with magnetized microbeads using magnetic resonance navigation in a controlled‐flow liver model

Michaud

Plantefève

et al. 2018

Medical Physics

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Purpose The purpose of this study was to demonstrate the feasibility of using a custom gradient sequence on an unmodified 3T magnetic resonance imaging (MRI) scanner to perform magnetic resonance navigation (MRN) by investigating the blood flow control method in vivo, reproducing the obtained rheology in a phantom mimicking porcine hepatic arterial anatomy, injecting magnetized microbead aggregates through an implantable catheter, and steering the aggregates across arterial bifurcations for selective tumor embolization. Materials and Methods In the first phase, arterial hepatic velocity was measured using cine phase‐contrast imaging in seven pigs under free‐flow conditions and controlled‐flow conditions, whereby a balloon catheter is used to occlude arterial flow and saline is injected at different rates. Three of the seven pigs previously underwent selective lobe embolization to simulate a chemoembolization procedure. In the second phase, the measured in vivo controlled‐flow velocities were approximately reproduced in a Y‐shaped vascular bifurcation phantom by injecting saline at an average rate of 0.6 mL/s with a pulsatile component. Aggregates of 200‐μm magnetized particles were steered toward the right or left hepatic branch using a 20‐mT/m MRN gradient. The phantom was oriented at 0°, 45°, and 90° with respect to the B0 magnetic field. The steering differences between left–right gradient and baseline were calculated using Fisher's exact test. A theoretical model of the trajectory of the aggregate within the main phantom branch taking into account gravity, magnetic force, and hydrodynamic drag was also designed, solved, and validated against the experimental results to characterize the physical limitations of the method. Results At an injection rate of 0.5 mL/s, the average flow velocity decreased from 20 ± 15 to 8.4 ± 5.0 cm/s after occlusion in nonembolized pigs and from 13.6 ± 2.0 to 5.4 ± 3.0 cm/s in previously embolized pigs. The pulsatility index measured to be 1.7 ± 1.8 and 1.1 ± 0.1 for nonembolized and embolized pigs, respectively, decreased to 0.6 ± 0.4 and 0.7 ± 0.3 after occlusion. For MRN performed at each orientation, the left–right distribution of aggregates was 55%, 25%, and 75% on baseline and 100%, 100%, and 100% (P < 0.001, P = 0.003, P = 0.003) after the application of MRN, respectively. According to the theoretical model, the aggregate reaches a stable transverse position located toward the direction of the gradient at a distance equal to 5.8% of the radius away from the centerline within 0.11 s, at which point the aggregate will have transited through a longitudinal distance of 1.0 mm from its release position. Conclusion In this study, we showed that the use of a balloon catheter reduces arterial hepatic flow magnitude and variation with the aim to reduce steering failures caused by fast blood flow rates and low magnetic steering forces. A mathematical model confirmed that the reduced flow rate is low enough to maximize steering ratio. After reproducing the flow rate in a vascular bifur...

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Injectable Shear‐Thinning Hydrogels with Sclerosing and Matrix Metalloproteinase Modulatory Properties for the Treatment of Vascular Malformations

Zehtabi,

Gangrade,

Tseng

et al. 2023

Adv Funct Materials

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Sac embolization of abdominal aortic aneurysms (AAAs) remains clinically limited by endoleak recurrences. These recurrences are correlated with recanalization due to the presence of endothelial lining and matrix metalloproteinases (MMPs)‐mediated aneurysm progression. This study incorporates doxycycline (DOX), a well‐known sclerosant and MMPs inhibitor, into a shear‐thinning biomaterial (STB)‐based vascular embolizing hydrogel. The addition of DOX is expected to improve embolizing efficacy while preventing endoleaks by inhibiting MMP activity and promoting endothelial removal. The results show that STBs containing 4.5% w/w silicate nanoplatelet and 0.3% w/v of DOX are injectable and have a twofold increase in storage modulus compared to those without DOX. STB‐DOX hydrogels also reduced clotting time by 33% compared to untreated blood. The burst release of DOX from the hydrogels show sclerosing effects after 6 h in an ex vivo pig aorta model. Sustained release of DOX from hydrogels on endothelial cells shows MMP inhibition (approximately an order of magnitude larger than control groups) after 7 days. The hydrogels successfully occlude a patient‐derived abdominal aneurysm model at physiological blood pressures and flow rates. The sclerosing and MMP inhibition characteristics in the engineered multifunctional STB‐DOX hydrogels may provide promising opportunities for the efficient embolization of aneurysms in blood vessels.

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

Abstract: N/A.

Cited by 17 publications

References 32 publications

Shear wave elasticity imaging for residual endoleak and thrombus characterisation after endoleak embolisation following endovascular aneurysm repair: a canine animal study

Shear wave elasticity imaging for residual endoleak and thrombus characterisation after endoleak embolisation following endovascular aneurysm repair: a canine animal study

Selective embolization with magnetized microbeads using magnetic resonance navigation in a controlled‐flow liver model

Injectable Shear‐Thinning Hydrogels with Sclerosing and Matrix Metalloproteinase Modulatory Properties for the Treatment of Vascular Malformations

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