Alginate-calcium microsphere loaded with thrombin: A new composite biomaterial for hemostatic embolization

Rong, Jingjing; Liang, Ming; Xuan, Fengqi; Sun, Jie; Zhao, Lijun; Zhen, Hui-zhen; Tian, Xiaoxiang; Liú, Dan; Zhang, Quan-yu; Peng, Chengfei; Tian-ming, Yao; Li, Fēi; Wang, Xiaozeng; Han, Yaling; Wu, Yu

doi:10.1016/j.ijbiomac.2014.12.043

Cited by 57 publications

(25 citation statements)

References 38 publications

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“…The hemostatic mechanism of TAMCs involves not only mechanical occlusion of mixed thrombin but also procoagulant activity of thrombin, sustainedly released from TACMs, which reinforce the mixed clots. In previous research, Rong et al found that one-week survival rate after embolization in TACMs mixed clots group is significantly higher compared with autologous clots group [16]. The results of this research further indicated that the clot strength of thrombus could be increased by adding TACMs to form mixed clot.…”

Section: Resultssupporting

confidence: 55%

“…Then, 3 mL whole blood was drawn from the artery sheath and was rapidly mixed with 0.5 mL TACMs in a 5 mL syringe to form TACMs and whole blood mixed clot as embolic agent. In order to site-specifically release the embolic agent with no complications related to the procedure, a special delivery method named “sandwich delivery” was performed [16]. By using guide wire, an angiography catheter was inserted along the sheath into the hepatic artery to perform angiography (Figure 1(a)).…”

Section: Methodsmentioning

confidence: 99%

“…In this study, we put forward an idea for preparing a kind of new embolic material, thrombin loaded alginate calcium microspheres (TACMs), which combine the advantage of embolic microspheres with the efficient procoagulant activity of thrombin. Rong et al have previously developed a novel application method of TACMs by mixing TACMs with whole blood in vitro to form a stronger mixed thrombus as embolic agent [16]. This study was conducted to evaluate biocompatibility of TACMs both in vitro and in vivo.…”

Section: Introductionmentioning

confidence: 99%

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

Xuan

Rong

Liang

et al. 2017

BioMed Research International

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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.

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Section: Resultssupporting

confidence: 55%

Section: Methodsmentioning

confidence: 99%

Section: Introductionmentioning

confidence: 99%

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

Xuan

Rong

Liang

et al. 2017

BioMed Research International

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“…40 Rong et al investigated in vivo degradation behavior of thrombin-loaded ALG-calcium microspheres after subcutaneous implantation in rats, revealing, through histological analyses, that only at 10 weeks it was not possible to identify microspheres anymore. 41 The biodegradation rate of coated P1 fibers depends not only on calcium-cross-linking of ALG but also on the ionic interaction between the carboxylate moieties of ALG and the protonated amines on CS. The soaking of P1 fibers in a CaCl 2 /CS solution promotes the formation of ALG-CS interactions, which have been reported to slow down polymer matrix degradation.…”

Section: Discussionmentioning

confidence: 99%

Coated electrospun alginate-containing fibers as novel delivery systems for regenerative purposes

Vigani

Rossi

Sandri

et al. 2018

IJN

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AimThe aim of the present work was to develop biodegradable alginate (ALG)-containing fibrous membranes intended for tissue repair, acting as both drug delivery systems and cell growth guidance.MethodsMembranes were prepared by electrospinning. Since ALG can be electrospun only when blended with other spinnable polymers, dextran (DEX) and polyethylene oxide (PEO) were investigated as process adjuvants. ALG/DEX mixtures, characterized by different rheological and conductivity properties, were prepared in phosphate buffer or deionized water; surfactants were added to modulate polymer solution surface tension. The Design of Experiments (DoE) approach (full factorial design) was used to investigate the role of polymer solution features (rheological properties, surface tension, and conductivity) on electrospun fiber morphology. A high viscosity at 1,000 s−1 (1.3–1.9 Pa.s) or a high pseudoplasticity index (≥1.7), combined with a low surface tension (30–32 mN/m) and a low conductivity (800–1,000 μS/cm), was responsible for the production of ALG/DEX homogeneous fibers. Such ranges were successfully employed for the preparation of ALG-containing fibers, using PEO, instead of DEX, as process adjuvant. ALG/DEX and ALG/PEO fibers were subsequently subjected to cross-linking/coating processes to make them slowly biodegradable in aqueous medium. In particular, ALG/PEO fibers were cross-linked and coated with CaCl2/chitosan solutions in water/ethanol mixtures. Due to DEX high content, ALG/DEX fibers were soaked in a polylactide-co-glycolide (PLGA) solution in ethyl acetate.ResultsBoth cross-linking and coating processes made fibers insoluble in physiological medium and produced an increase in their mechanical resistance, assessed by means of a tensile test. PLGA-coated ALG/DEX and chitosan-coated ALG/PEO fibers were biocompatible and able to support fibroblast adhesion.ConclusionThe DoE approach allowed to draw up guidelines useful for the preparation of homogeneous fibers, starting from mixtures of ALG and non-ionic polymers. Such fibers, upon coating, resulted to be good cell substrates, allowing cell adhesion and growth.

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“…Besides the traditional hydrogelic form, the alginate material can also be made into micro/nanoparticles as well as micro/nanofiber using suitable processing techniques, and these solid forms have been recently evaluated in hemostatic applications. Alginate microspheres loaded with the antifibrinolytic agent tranexamic acid or the procoagulant agent thrombin, have shown promising hemostatic capabilities in vitro and in vivo in preclinical models . Currently a large number of alginate‐based wound dressings are clinically approved for surgical and hemostatic applications, e.g., Algosteril (Johnson & Johnson, USA) and KALTOSTAT (Conva Tec, UK).…”

Section: Hemostatic Biomaterials and Technologies For Topical (Externmentioning

confidence: 99%

Biomaterials and Advanced Technologies for Hemostatic Management of Bleeding

et al. 2017

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Bleeding complications arising from trauma, surgery, and as congenital, disease-associated, or drug-induced blood disorders can cause significant morbidities and mortalities in civilian and military populations. Therefore, stoppage of bleeding (hemostasis) is of paramount clinical significance in prophylactic, surgical, and emergency scenarios. For externally accessible injuries, a variety of natural and synthetic biomaterials have undergone robust research, leading to hemostatic technologies including glues, bandages, tamponades, tourniquets, dressings, and procoagulant powders. In contrast, treatment of internal noncompressible hemorrhage still heavily depends on transfusion of whole blood or blood's hemostatic components (platelets, fibrinogen, and coagulation factors). Transfusion of platelets poses significant challenges of limited availability, high cost, contamination risks, short shelf-life, low portability, performance variability, and immunological side effects, while use of fibrinogen or coagulation factors provides only partial mechanisms for hemostasis. With such considerations, significant interdisciplinary research endeavors have been focused on developing materials and technologies that can be manufactured conveniently, sterilized to minimize contamination and enhance shelf-life, and administered intravenously to mimic, leverage, and amplify physiological hemostatic mechanisms. Here, a comprehensive review regarding the various topical, intracavitary, and intravenous hemostatic technologies in terms of materials, mechanisms, and state-of-art is provided, and challenges and opportunities to help advancement of the field are discussed.

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Alginate-calcium microsphere loaded with thrombin: A new composite biomaterial for hemostatic embolization

Cited by 57 publications

References 38 publications

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

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

Coated electrospun alginate-containing fibers as novel delivery systems for regenerative purposes

Biomaterials and Advanced Technologies for Hemostatic Management of Bleeding

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