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Platelet-like particles for augmenting hemostasis

用于增强止血的类血小板颗粒

基本信息

批准号：
9187716
负责人：
Thomas Harrison Barker
金额：
$ 70.55万
依托单位：
UNIVERSITY OF VIRGINIA
依托单位国家：
美国
项目类别：
财政年份：
2016
资助国家：
美国
起止时间：
2016-07-01 至 2020-06-30
项目状态：
已结题

来源：
https://reporter.nih.gov/project-details/9187716
关键词：
Advanced Development Adverse effects Affinity Antibodies Binding Biocompatible Materials Biomedical Engineering Biophysics Biotechnology Bleeding time procedure Blood Coagulation Disorders Blood Coagulation Factor Blood Platelets Blood Tests Blood Vessels Cardiopulmonary Bypass Cause of Death Cells Chemistry Clinical Clinical Medicine Clinical Trials Coagulants Coagulation Process Consumption Contracts Coupled Development Discipline Emergency Medicine Ensure Failure Fiber Fibrin Fibrinogen Formulation Functional disorder Goals Growth Hemorrhage Hemostatic Agents Hemostatic function Human Hydrogels In Vitro Injury Lead Life Microfluidics Modeling Molecular Molecular Evolution Morbidity - disease rate Nature Operative Surgical Procedures Peptide Hydrolases Physical Chemistry Physics Plasma Platelet Transfusion Polymers Pre-hospital setting Process Protein Engineering Protein Precursors Publishing Recombinants Records Regulation Research Research Personnel Risk Rodent Science Site Source Specificity Staging Structure System Techniques Technology Testing Thrombin Thrombosis Trauma Traumatic injury Work Zeolites abstracting analog antibody engineering base crosslink design effective therapy in vivo innovation mimetics mortality mouse model novel particle poly-N-isopropylacrylamide polymerization spatiotemporal stem success synthetic biology wound

项目摘要

Project Abstract Uncontrolled bleeding represents a significant clinical challenge in general surgery, trauma, and emergency medicine. Exsanguination (bleeding) is the major cause of death from traumatic injury (~ 40%) and bleeding following invasive surgeries such as cardiopulmonary bypass is associated with significant morbidity and mortality. During the normal clotting cascade, the protease thrombin is activated, which in turn activates dormant circulating platelets and the clotting protein precursor, fibrinogen. Activated platelets form a hemostatic plug at the site of injury, stemming blood loss. Platelets are sufficient to achieve short-term hemostasis and are critical to the maturation of stable fibrin-based clots via their activity in fibrin recruitment and clot contraction. Thus, it is not surprising that their massive dilution during hemorrhage or active inhibition during surgery results in a failure of the clotting system. Current hemostasis technologies include topical sealants, exothermic zeolites and recombinant clotting factors. Each of these approaches has demonstrated modest successes, yet all have significant drawbacks such as a lack of wound specificity; none are as “evolved” as the natural wound-responsive hemostasis system. Thus, more recent efforts have focused on creation of synthetic analogs of platelets. The vital platelet functions that one would like to recapitulate include injury-triggered enhancement of fibrin clot formation and clot contraction/stabilization. To date, artificial platelet approaches only recapitulate clot/platelet binding in a non-triggered (i.e. constitutive) and non-specific fashion and lack the other critical platelet functions. Here we propose a novel and simple approach to the creation of platelet-like structures through the application of synthetic biology. We are proposing two aims. The first aim is to understand how our platelet-like particles interact with various stages of the coagulation cascade and to understand the fundamental mechanism of action of our platelet-like particles in augmenting hemostasis. The second aim is to explore the in vivo function of the platelet-like particles, specifically in the augmentation of hemostasis in multiple models of trauma-associated coagulopathy.

项目摘要