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In vitro and in vivo anticoagulant activity of heparin-like biomacromolecules and the mechanism analysis for heparin-mimicking activity

Author:
Ma, Lang, Huang, Jianbo, Zhu, Xiaoxia, Zhu, Bihui, Wang, Liyun, Zhao, Weifeng, Qiu, Li, Song, Bin, Zhao, Changsheng, Yan, Feng
Source:
International journal of biological macromolecules 2019 v.122 pp. 784-792
ISSN:
0141-8130
Subject:
Fourier transform infrared spectroscopy, anticoagulant activity, anticoagulants, biocompatibility, biopolymers, coagulation, complement, hemolysis, heparin, histopathology, medical equipment, models, moieties, nuclear magnetic resonance spectroscopy, rats, sodium alginate, toxicity
Abstract:
Heparin-like biomacromolecules (HepLBm), exhibiting similar chemical structure and biological properties to heparin, can be obtained by modifying either synthetic biopolymers or natural biomacromolecules with physical or chemical methods. In this work, a low-cost and biocompatible sodium alginate was chosen as a model biomacromolecule to design anticoagulant HepLBm with a similar sulfation degree to heparin. FTIR, 1H NMR, and element analysis data were used to confirm the chemical structure of HepLBm. Hemolysis tests, clotting time, complement activation, and contact activation tests were carried out to determine the in vitro anticoagulant activity of HepLBm. In addition, systematic studies of blood cell count, coagulation function, and histopathology were performed to demonstrate the in vivo anticoagulant activity and toxicity of HepLBm with SD rat experiments. Furthermore, a series of linear molecules containing carboxyl groups, sulfonic groups, and hydroxyl groups were selected and their clotting time was tested to provide a mechanism analysis for the excellent anticoagulant activity of HepLBm. With the excellent in vitro/in vivo anticoagulant activity, good biocompatibility, and low cost, the HepLBm synthesized in this work would have great potential for substitution of heparin in many application fields, such as the surface modification of biomedical devices, extracorporeal anticoagulants, and other clinical fields.
Agid:
6264717