Platelet Production in a Pulmonary-based Microfluidic Reactor

基于肺的微流体反应器中的血小板生产

• 批准号: 9907840
• 负责人: ALI YEHIA
• 金额: $ 30.86万
• 依托单位: FLUXION BIOSCIENCES, INC.
• 依托单位国家: 美国
• 财政年份: 2020
• 资助国家: 美国
• 起止时间: 2020-06-01 至 2021-11-30
• 项目状态: 已结题
• 来源: https://reporter.nih.gov/project-details/9907840
• 关键词: Address; Agonist; Alternative Therapies; Beds; Binding; Biological; Biology; Biomedical Engineering; Blood; Blood Platelet Disorders; Blood Platelets; Blood flow; Bone Marrow; Caring; Characteristics; Clinic; Clinical; Collaborations; Data; Development; Devices; Dimensions; Endothelium; Environment; Future; Gases; Generations; Geometry; Human; Immobilization; In Vitro; Infusion procedures; Laboratories; Lead; Lung; Malignant Neoplasms; Measurement; Measures; Mechanical Stimulation; Mechanics; Megakaryocytes; Microfluidic Microchips; Microfluidics; Microscopic; Modeling; Modern Medicine; Partial Pressure; Patients; Performance; Periodicity; Phase; Physiological; Platelet Count measurement; Platelet Transfusion; Production; Property; Pulmonary Gas Exchange; Reporting; Research; Research Project Grants; Rest; Risk; Safety; Stream; Surface; System; Testing; Thinness; Thrombopoiesis; Time; Transfusion; Venous; Work; base; capillary bed; demographics; design; disease transmission; flexibility; improved; in vivo; instrument; mechanical drive; mimetics; particle; platelet function; post-trauma; pressure; response; scale up; success; systems research; tool; vascular bed

ABSTRACT Platelet transfusions are used to treat deficiencies in platelet number and/or function that is seen in multiple clinical settings such as cancer and post trauma. Given changing demographics and an increasing reliance on platelet transfusion in modern medicine, its is likely that donor-derived platelets to provide this care may prove inadequate in the near future. The generation of large numbers of physiologically viable platelets in-vitro is intended to provide a new treatment option for such patients with platelet deficies. Starting with mega- karyocytes (Megs), platelet release (thrombopoiesis) is driven by shear forces typically found in the vasculatures. Previous approaches were aimed at mimicking platelet production in the bone marrow as Megs emerge from the intramedullary space into the blood stream, but new research points to significant platelet production by Megs embedded in the lung. This proposal is aimed at taking advantage of this discovery to improve both our understanding of thrombopoiesis and our ability to produce platelets in vitro focused on mimicking the particular properties of the pulmonary microvasculature. There are four aims in this application: Aim 1: Produce and test devices recapitulating the pulmonary vascular bed. Several different will be manufactured to entrap Megs and allow thrombopoiesis to occur. Aim 2: Design and test a system for platelet production under lung-mimetic mechanical strain. We will use flexible microfluidic layers will b. Aim 3: Design and test a system for temporal control of O2 concentration within the reactor. Switching from a low to high O2 partial will be achieved to replicated physiological changes in the lung. Aim 4: Optimize the combined effects of lung model parameters and test platelet functional performance. The final microfluidic devices using all of the optimal parameter determined will be tested by infusions of Megs and measurement of the efficacy to produce platelet-like particles that physically and functionally match that of freshly-drawn donor-derived platelets. Phase I research is intended to validate a consumable compatible with existing controllers that can we used widely to study platelet production lung microenvironment by controlling cappillary, shear forces, defomation of capillary bed and gas concentration. If successful, a scale-up to a clinically feasible platelet production reactor will be attepted in Phase II. This work represents a collaboration between a bioengineering company that has been supplying microfluidic research systems for the study of platelet function and a laboratory that are domain experts in the treatment of platelet disorders.

抽象的 血小板输血用于治疗血小板数和/或功能中的缺陷 临床环境，例如癌症和创伤后。考虑到不断变化的人口统计信息，并且越来越依赖 现代医学中的血小板输血，提供此护理的捐赠者衍生的血小板可能证明 在不久的将来不足。大量生理可行的血小板在体外的生成 旨在为此类血小板缺乏症患者提供新的治疗选择。从Mega开始 核细胞（MEGS），血小板释放（血小板）由通常在 血管。先前的方法旨在模仿骨髓中的血小板产生 从髓内空间出现到血流，但新的研究表明了明显的血小板 MEGS的生产嵌入了肺中。该建议旨在利用这一发现 提高我们对血小板的理解以及我们在体外产生血小板的能力。 模仿肺微血管的特定特性。 此应用中有四个目标：目标1：生产和测试设备，概括肺部 血管床。将制造几种不同的人来捕捉MEG，并允许发生血小板。目的 2：在肺模仿机械应变下设计和测试血小板产生的系统。我们将使用 柔性微流体层将b。 AIM 3：设计和测试一个用于O2浓度的时间控制的系统 在反应堆内。从低o2部分转换为复制生理变化 在肺部。 AIM 4：优化肺模型参数和测试血小板功能的组合效应 表现。使用所有最佳参数确定的最终微流体设备将通过 MEG的输注和测量功效，产生了物理和 在功能上与新鲜供体衍生的血小板相匹配。 第一阶段的研究旨在验证与现有控制器兼容的消耗量 广泛研究血小板生产肺微环境，通过控制粘质，剪切力，畸形 毛细管床和气体浓度。如果成功，则对临床上可行的血小板生产反应堆进行扩展 将在第二阶段进行。这项工作代表了一家生物工程公司之间的合作 一直在提供微流体研究系统，用于研究血小板功能和实验室，它们是领域 血小板疾病治疗的专家。