Blood-contacting materials with good mechanical property, excellent anticoagulant function and promoting effect on endothelialization are in great demand for clinical application such as vascular grafts in treating cardiovascular diseases. In this study, electrospinning nanofiber scaffolds of polycaprolactone (PCL) were functionalized by oxidative self-polymerization of dopamine (PDA) on the surface followed by the modification of anticoagulant recombinant hirudin (rH) molecules. The morphology, structure, mechanical property, degradation behavior, cellular compatibility and blood compatibility of the multifunctional PCL/PDA/rH nanofiber scaffolds were evaluated. The diameter of the nanofibers was between 270-1030 nm. The ultimate tensile strength of the scaffolds was around 4 MPa and the elastic modulus increased with the amount of rH. The degradation tests in vitro indicated that the nanofiber scaffolds began to crack on the 7th day, but still maintained the nanoscale architecture within a month. The cumulative release of rH from the nanofiber scaffold was up to 95.9 % at 30th day. The functionalized scaffolds promoted the adhesion and proliferation of endothelial cells, while resisting platelet adhesion and enhancing anticoagulation effects. The hemolysis ratios of all scaffolds were <2 %. The nanofiber scaffolds are promising candidates for vascular tissue engineering.

01 Jul 2021·Critical Care ClinicsQ3 · MEDICINE

Antithrombotic and Antiplatelet Drug Toxicity

Q3 · MEDICINE

Review

Author: Mullins, Michael E ; Liss, David B

Anticoagulant and antiplatelet drugs target a specific portion of the coagulation cascade or the platelet activation and aggregation pathway. The primary toxicity associated with these agents is hemorrhage. Understanding the pharmacology of these drugs allows the treating clinician to choose the correct antidotal therapy. Reversal agents exist for some of these drugs; however, not all have proven patient-centered outcomes. The anticoagulants covered in this review are vitamin K antagonists, heparins, fondaparinux, hirudin derivatives, argatroban, oral factor Xa antagonists, and dabigatran. The antiplatelet agents reviewed are aspirin, adenosine diphosphate antagonists, dipyridamole, and glycoprotein IIb/IIIa antagonists. Additional notable toxicities are also reviewed.

01 Nov 2020·Journal of BiotechnologyQ3 · ENGINEERING & TECHNOLOGY

Enhanced anticoagulant activity of hirudin-i analogue co-expressed with arylsulfotransferase in periplasm of E. coli BL21(DE3)

Q3 · ENGINEERING & TECHNOLOGY

Article

Author: Liang, Yunlong ; Rai, Kamal ; Bao, Zixian ; Nian, Rui ; Chu, Xiaohui ; Yang, Junqing ; Sun, Yue ; Wang, Xingang ; Xian, Mo

Hirudin, a blood anticoagulant, is the most potent natural thrombin inhibitor of leech origin. Its application is limited because it is difficult to obtain abundant natural hirudin directly from the leech. Although some bioengineering methods can significantly increase the production of hirudin, the reduced efficacy of recombinant hirudin (rH) remains a critical shortcoming. The lack of sulfation of tyrosine 63 in rH is an important cause of its inadequate performance. This article is the first report of periplasmic co-expression of an rH-I analogue with arylsulfotransferase (ASST) in E. coli BL21(DE3). Co-expressed rH-I analogue with sulfate donor substrate (p-nitrophenyl sulfate potassium) showed anticoagulant (rabbit and goat serum) activity twice more than rH-I analogue expressed without ASST, indicating its potential periplasmic sulfation. Moreover, purified rH-I analogue showed above 4.5 times higher anticoagulant activity compared to therapeutic anti-thrombotic heparin (HE). At the same time, pH-dependent differential solubility was employed to purify rH analogues from fermentation broth, which is a simple, fast and inexpensive purification technology, and can potentially be used for larger scale purification. This will also greatly improve the application of rH in clinical treatment.

100 Deals associated with Recombinant hirudin(China Resources Angde Biotech Pharma Co., Ltd.)

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Indication	Highest Phase	Country/Location	Organization	Date
Thrombosis	IND Application	CN	China Resources Angde Biotech Pharma Co., Ltd.	02 Apr 2001

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