Biocompatibility and Effectiveness Evaluation of a New Hemostatic Embolization Agent: Thrombin Loaded Alginate Calcium Microsphere

Abstract

Background. Until now, there has been no ideal embolization agent for hemorrhage in interventional treatment. In this study, the thrombin was encapsulated in alginate calcium microsphere using electrostatic droplet technique to produce new embolization agent: thrombin loaded alginate calcium microspheres (TACMs). Objectives. The present work was to evaluate the biocompatibility and hemostatic efficiency of TACMs. Methods. Cell cytotoxicity, hemolysis, and superselective embolization of dog liver arteries were performed to investigate the biocompatibility of TACMs. To clarify the embolic effect of TACMs mixed thrombus in vivo, hepatic artery injury animal model of 6 beagles was established and transcatheter artery embolization for bleeding was performed. Results. Coculture with VECs revealed the noncytotoxicity of TACMs, and the hemolysis experiment was negligible. Moreover, the histological study of TACMs in liver blood vessel showed signs of a slight inflammatory reaction. The results of transcatheter application of TACMs mixed thrombus for bleeding showed that the blood flow was shut down completely after the TACMs mixed thrombus was delivered and the postprocedural survival rate of animal models at 12 weeks was 100%. Conclusions. With their good biocompatibility and superior hemostatic efficiency, TACMs might be a promising new hemostatic agent with a wide range of potential applications.

Advances in Biomaterials and Technologies for Vascular Embolization

“…Thrombin was also encapsulated into alginate calcium microspheres (TACMs) through an electrostatic droplet technique, without the need of either high temperatures or crosslinking agents. [242] This approach enabled the production of compressible and monodispersed microspheres with average diameter of 350 μm. Superselective hepatic artery embolization was conducted in a canine model and was successful in all animals during a 90-day observation period.…”

“…The hemostatic mechanism of the TACMs combined with the mechanical occlusion of the blood vessels and procoagulant activities induced by the thrombin release from the TACMs could reinforce the particle/clot complexes. [242] TACMs are simple to fabricate, hemocompatible, biocompatible, and exhibit long-term hemostasis, revealing their potential as a new hemostatic embolic material for interventional applications.…”

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

“…One of the critical prerequisites of the embolic agents to be used in contact with the blood should not induce hemolysis upon implantation [ 51 , 52 ]. Thus, the hemolysis behavior of the BaSO 4 /PVA/CS MS was evaluated by incubating the MS with fresh rabbit blood.…”

Regulation of the Ocular Cell/Tissue Response by Implantable Biomaterials and Drug Delivery Systems

“…Alginate is another natural polysaccharide made of linear unbranched copolymers (1-4)-linked β-d-mannuronic acid and (1-4)-linked α-l-guluronic acid. Biocompatibility, biodegradability, and ease of chemical modification make alginate a suitable vehicle for delivery of a wide range of bioactive molecules such as those used in ocular tissue repair [120,121]. Improved ocular bioavailability of various types of drugs (e.g., lutein) is achievable via their administration by alginate and its composites [122].…”