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Development and thromboelastographic characterization of new hemostatic agents with potential for surgical and dental applications aiming at anti-hemorrhagic treatment

Abstract

Despite advances in medical intervention, hemorrhagic complications continue to be a leading cause of death worldwide. Thus, the development of effective methods for the treatment of uncontrolled bleeding has become a top priority in several medical research centers. By definition an ideal hemostatic agent should have the ability to stop arterial and venous bleeding, be available for immediate use, be functional and easy to apply, lightweight, durable, stable and safe and low cost. There are currently hemostatic agents on the market made from inorganic and organic materials, or even composites. Among the organic materials stands out the group of hemostatic agents made from natural biopolymers such as chitosan and cellulose. The set of certain inherent characteristics of such biopolymers such as the size of their molecular chains, the possibility and facility of modulating the charge density of such chains, controlling the degree of crystallinity, the outer surface area, the degree of hydrophobicity / hydrophilicity, and biocompatibility favor its use as raw material for the production of topical hemostatic agents. The hemostatic potential of biopolymers such as chitosan and cellulose led to the development and commercialization of products such as Surgicel (a cellulose-based product marketed by Johnson-Jonhson) and Lyostypt® and Hemocon (a chitosan based product marketed by Tricol Biomedical Inc. ). Although the biopolymers chitosan and cellulose find applications as hemostatic agents, the same does not occur with another biopolymer abundant in Brazilian biomass: pectin. Chemically pectin consists essentially of partial methyl esters of polygalacturonic acid with a maximum molecular weight of 150,000 Daltons, which can be obtained by aqueous extraction of an edible vegetable material (usually citrus fruit or apple), followed by a selective precipitation made with the use of alcohol and salts.Citrus fruits and apples have a high concentration of pectin and are available in sufficient quantity to make their industrialization process economically feasible, since they are already part of an abundant biomass resulting from the final end of a production chain already strongly established in the economy (in the case to citrus juice industry).The proposal of this research project is the systematic study of the potential of biopolymer pectin and its derivatives as possible hemostatic agents for use in surgical and dental applications. In this project, new hemostatic agents based on pectin will be synthesized, characterized by different spectroscopic techniques, and systematically modulated to act with greater efficiency in the coagulation cascade. The study of the hemostatic action of the new agents derived from pectin will be done in vitro, using thromboelastographic analyzes, compared to the action of haemostatic agents based on chitosan, cellulose and zeolites. The main variables studied will be: the time reaction to form a clot of approximately 2 mm in size, which characterizes the onset of fibrin production, b) the time of formation of a firm clot of 20 mm and the rate of generation of thrombin and the conversion of fibrinogen to fibrin, c) elastic property of fibrin formed and platelet adhesion. The thromboelastographic tests will be performed in cooperation with the Blood Institute of São José do Rio Preto Medical School (FAMERP), using blood samples from volunteer patients of the following groups: normal patients with congenital deficiency of coagulation factors (thrombophilia and hemophilia), patients with acquired coagulation factor deficiency (chronic liver diseases). (AU)

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Scientific publications
(References retrieved automatically from Web of Science and SciELO through information on FAPESP grants and their corresponding numbers as mentioned in the publications by the authors)
CONTRO, JANINE; SILVA, DANILO ANTONIO; SANTISTEBAN, OSCAR A. N.; NARAYANA, PONNADA A.; NERY, JOSE G. In vitro and in vivo comparative performance studies of gadolinium-loaded zeolites and Gd-DOTA as contrast agents for MRI applications. JOURNAL OF BIOMEDICAL MATERIALS RESEARCH PART B-APPLIED BIOMATERIALS, DEC 2020. Web of Science Citations: 0.
MEDEIROS, VINICIUS LITRENTA; DE ARAUJO, LEANDRO GOULART; RATERO, DAVI RUBINHO; PAULA, ALEX SILVA; MOLINA, EDUARDO FERREIRA; JAEGER, CHRISTIAN; MARUMO, JULIO TAKEHIRO; NERY, JOSE GERALDO. Synthesis and physicochemical characterization of a novel adsorbent based on yttrium silicate: A potential material for removal of lead and cadmium from aqueous media. JOURNAL OF ENVIRONMENTAL CHEMICAL ENGINEERING, v. 8, n. 4 AUG 2020. Web of Science Citations: 0.

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