Anti-thrombotic technologies for medical devices

Lavery, Karen; Rhodes, Candace; McGraw, Adam P.; Eppihimer, Michael J.

doi:10.1016/j.addr.2016.07.008

Cited by 77 publications

(71 citation statements)

References 128 publications

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“…Herein, in addition to its good mechanical strength, processability, biocompatibility, and mild degradation products, a prerequisite for constructing PCL into small‐diameter off‐the‐ shelf TEVGs with long‐term patency is endowing it with sustainable anticoagulation activity. Heparin is a natural anticoagulant substance and has a long history for use in thromboembolic diseases, myocardial infarction, cardiovascular surgery, cardiac catheterization, cardiopulmonary bypass, hemodialysis, and so on . The end‐group heparinization is an effective method to improve anticoagulation and achieve sustained heparin release of the PCL‐based TEVGs.…”

Section: Discussionmentioning

confidence: 99%

“…Heparin is a natural anticoagulant substance and has a long history for use in thromboembolic diseases, myocardial infarction, cardiovascular surgery, cardiac catheterization, cardiopulmonary bypass, hemodialysis, and so on. [26] The end-group heparinization is an effective method to improve anticoagulation and achieve sustained heparin release of the PCL-based TEVGs. As a result, the end-group heparinized PCL of M n = 4.5 × 10 4 was synthesized by a three-step process and then electrospun into an inner layer of the DLVSs in this study.…”

Section: Discussionmentioning

confidence: 99%

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Preparation of Small‐Diameter Tissue‐Engineered Vascular Grafts Electrospun from Heparin End‐Capped PCL and Evaluation in a Rabbit Carotid Artery Replacement Model

Jin

Geng

Jia³

et al. 2019

Macromolecular Bioscience

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Aiming to construct small diameter (ID <6 mm) off‐the‐shelf tissue‐engineered vascular grafts, the end‐group heparinizd poly(ε‐caprolactone) (PCL) is synthesized by a three‐step process and then electrospun into an inner layer of double‐layer vascular scaffolds (DLVSs) showing a hierarchical double distribution of nano‐ and microfibers. Afterward, PCL without the end‐group heparinization is electrospun into an outer layer. A steady release of grafted heparin and the existence of a glycocalyx structure give the grafts anticoagulation activity and the conjugation of heparin also improves hydrophilicity and accelerates degradation of the scaffolds. The DLVSs are evaluated in six rabbits via a carotid artery interpositional model for a period of three months. All the grafts are patent until explantation, and meanwhile smooth endothelialization and fine revascularization are observed in the grafts. The composition of the outer layer of scaffolds exhibits a significant effect on the aneurysm dilation after implantation. Only one aneurysm dilation is detected at two months and no calcification is formed in the follow‐up term. How to prevent aneurysms remains a challenging topic.

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Section: Discussionmentioning

confidence: 99%

Section: Discussionmentioning

confidence: 99%

Preparation of Small‐Diameter Tissue‐Engineered Vascular Grafts Electrospun from Heparin End‐Capped PCL and Evaluation in a Rabbit Carotid Artery Replacement Model

Jin

Geng

Jia³

et al. 2019

Macromolecular Bioscience

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“…Blood‐contacting medical devices, including catheters, stents, grafts, filters, and extracorporeal organ support (ECOS) systems can fail due to thrombus accumulation in the system and may also trigger device‐associated thromboembolism . To maintain patency, devices that are perfused for various lengths of time require prophylactic anticoagulation, which can increase the incidence and/or severity of bleeding.…”

Section: Introductionmentioning

confidence: 99%

Antibody inhibition of contact factor XII reduces platelet deposition in a model of extracorporeal membrane oxygenator perfusion in nonhuman primates

Wallisch

Lorentz

Lakshmanan

et al. 2020

Research and Practice in Thrombosis and Haemostasis

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Background The contact factor XII (FXII) activates upon contact with a variety of charged surfaces. Activated FXII (FXIIa) activates factor XI, which activates factor IX, resulting in thrombin generation, platelet activation, and fibrin formation. In both in vitro and in vivo rabbit models, components of medical devices, including extracorporeal oxygenators, are known to incite fibrin formation in a FXII‐dependent manner. Since FXII has no known role in hemostasis and its inhibition is therefore likely a safe antithrombotic approach, we investigated whether FXII inhibition also reduces accumulation of platelets in extracorporeal oxygenators. Objectives We aimed to determine the effect of FXII inhibition on platelet deposition in perfused extracorporeal membrane oxygenators in nonhuman primates. Methods A potent FXII neutralizing monoclonal antibody, 5C12, was administered intravenously to block contact activation in baboons. Extracorporeal membrane oxygenators were temporarily deployed into chronic arteriovenous access shunts. Radiolabeled platelet deposition in oxygenators was quantified in real time using gamma camera imaging. Biochemical assays were performed to characterize the method of action of 5C12. Results The anti‐FXII monoclonal antibody 5C12 recognized both the alpha and beta forms of human and baboon FXII by binding to the protease‐containing domain, and inhibited FXIIa activity. Administration of 5C12 to baboons reduced platelet deposition and fibrin formation in the extracorporeal membrane oxygenators, in both the presence and absence of systemic low‐dose unfractionated heparin. The antiplatelet dose of 5C12 did not cause measurable increases in template bleeding times in baboons. Conclusions FXII represents a possible therapeutic and safe target for reducing platelet deposition and fibrin formation during medical interventions including extracorporeal membrane oxygenation.

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“…In vitro endothelialization directly seeds autologous endothelial cells to form a monolayer along the internal surface of synthetic vascular grafts. While effective at reducing stenosis and thrombosis of grafts, it is a technically difficult process that can take months to years to complete, and it is difficult to achieve complete endothelialization of even modest‐length devices such as grafts and stents 57,60 . It is currently not technically feasible due to the large surface area of an ECMO circuit requiring coverage, nor to produce this in an urgent or emergent fashion.…”

Section: Ecmo Circuit Materialsmentioning

confidence: 99%

Hematologic concerns in extracorporeal membrane oxygenation

Sniderman

Monagle

Annich

et al. 2020

Research and Practice in Thrombosis and Haemostasis

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This ISTH “State of the Art” review aims to critically evaluate the hematologic considerations and complications in extracorporeal membrane oxygenation (ECMO). ECMO is experiencing a rapid increase in clinical use, but many questions remain unanswered. The existing literature does not address or explicitly state many pertinent details that may influence hematologic complications and, ultimately, patient outcomes. This review aims to broadly introduce modern ECMO practices, circuit designs, circuit materials, hematologic complications, transfusion‐related considerations, age‐ and size‐related differences, and considerations for choosing outcome measures. Relevant studies from the 2019 ISTH Congress in Melbourne, which further advanced our understanding of these processes, will also be highlighted.

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Anti-thrombotic technologies for medical devices

Cited by 77 publications

References 128 publications

Preparation of Small‐Diameter Tissue‐Engineered Vascular Grafts Electrospun from Heparin End‐Capped PCL and Evaluation in a Rabbit Carotid Artery Replacement Model

Preparation of Small‐Diameter Tissue‐Engineered Vascular Grafts Electrospun from Heparin End‐Capped PCL and Evaluation in a Rabbit Carotid Artery Replacement Model

Antibody inhibition of contact factor XII reduces platelet deposition in a model of extracorporeal membrane oxygenator perfusion in nonhuman primates

Hematologic concerns in extracorporeal membrane oxygenation

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