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Immobilized thrombin on X-ray radiopaque polyvinyl alcohol/chitosan embolic microspheres for precise localization and topical blood coagulation.

ABSTRACT: Trans-catheter arterial embolization (TAE) plays an important role in treating various diseases. The available embolic agents lack X-ray visibility and do not prevent the reflux phenomenon, thus hindering their application for TAE therapy. Herein, we aim to develop a multifunctional embolic agent that combines the X-ray radiopacity with local procoagulant activity. The barium sulfate nanoparticles (BaSO₄ NPs) were synthesized and loaded into the polyvinyl alcohol/chitosan (PVA/CS) to prepare the radiopaque BaSO₄/PVA/CS microspheres (MS). Thereafter, thrombin was immobilized onto the BaSO₄/PVA/CS MS to obtain the thrombin@BaSO₄/PVA/CS MS. The prepared BaSO₄/PVA/CS MS were highly spherical with diameters ranging from 100 to 300 μm. In vitro CT imaging showed increased X-ray visibility of BaSO₄/PVA/CS MS with the increased content of BaSO₄ NPs in the PVA/CS MS. The biocompatibility assessments demonstrated that the MS were non-cytotoxic and possessed permissible hemolysis rate. The biofunctionalized thrombin@BaSO₄/PVA/CS MS showed improved hemostatic capacity and facilitated hemostasis in vitro. Additionally, in vivo study performed on a rabbit ear embolization model confirmed the excellent X-ray radiopaque stability of the BaSO₄/PVA/CS MS. Moreover, both the BaSO₄/PVA/CS and thrombin@BaSO₄/PVA/CS MS achieved superior embolization effects with progressive ischemic necrosis on the ear tissue and induced prominent ultrastructural changes in the endothelial cells. The findings of this study suggest that the developed MS could act as a radiopaque and hemostatic embolic agent to improve the embolization efficiency.

SUBMITTER: Li X

PROVIDER: S-EPMC7807145 | biostudies-literature |

REPOSITORIES: biostudies-literature

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Project description:ObjectivesTract embolization has been performed to prevent bleeding after trans-organ puncture. This study evaluated clinical outcomes of tract embolization using a gel-like radiopaque material comprising two sheets of gelatin sponge and 3 mL of contrast agent, and experimentally confirmed its viscosity and hemostatic efficacy.MethodsThree study phases were planned. In a clinical setting, 57 consecutive patients who underwent tract embolization after transhepatic puncture were retrospectively analyzed. Clinical success was evaluated as absence of bleeding complications for 30 days after the procedure. In a basic experiment, viscosity of the material was analyzed. In an animal experiment, rabbit kidney puncture site was embolized via a 7-Fr sheath using this material, coils, or N-butyl-2-cyanoacrylate glue or received no embolization while removing the sheath. Amounts of tract bleeding were measured for 1 min and compared between groups.ResultsEmbolization was successfully completed in all clinical cases. No postoperative bleeding requiring intervention was encountered. The basic experiment revealed the material was highly viscous. In the animal experiment, mean weights of bleeding in the control, gel-like embolic material, coil, and N-butyl-2-cyanoacrylate glue groups were 1.04±0.32 g, 0.080±0.056 g, 0.20±0.17 g and 0.11±0.10 g, respectively. No significant differences were seen among embolization groups, while the control group showed significantly more bleeding than any embolization group.ConclusionTract embolization with this gel-like radiopaque embolic material appears safe and feasible.Advances in knowledgeTract embolization using this embolic material with two sheets of gelatin sponge and 3 mL of contrast agent offers a safe, feasible, and economical procedure after trans-organ puncture, because the material offers the following characteristics: visibility under X-ray; viscosity facilitating retention in the tract; ability to allow repeated puncture via the same route; and low cost.

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Immobilized thrombin on X-ray radiopaque polyvinyl alcohol/chitosan embolic microspheres for precise localization and topical blood coagulation.

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