Biomimetic Design and Construction of an Artificial Lung

人工肺的仿生设计与构造

• 批准号: 8197702
• 负责人: Jeffrey T. Borenstein
• 金额: $ 30.58万
• 依托单位: CHARLES STARK DRAPER LABORATORY
• 依托单位国家: 美国
• 财政年份: 2010
• 资助国家: 美国
• 起止时间: 2010-12-01 至 2013-11-30
• 项目状态: 已结题
• 来源: https://reporter.nih.gov/project-details/8197702
• 关键词: Acute; Acute Lung Injury; Address; Adult Respiratory Distress Syndrome; Adverse event; Anticoagulation; Architecture; Artificial Respiration; Biomedical Engineering; Biomimetics; Blood; Blood Vessels; Blood Volume; Blood flow; Cardiopulmonary; Cause of Death; Chronic; Chronic Disease; Chronic Obstructive Airway Disease; Chronic lung disease; Clinical; Coagulation Process; Development; Devices; Disease; Elements; Failure; Future; Gases; Goals; Heart Diseases; Home environment; Human; Hypoxia; Infection; Injury; Lead; Left; Life; Lung; Lung Transplantation; Malignant Neoplasms; Mechanical ventilation; Medical Device; Membrane; Membrane Oxygenators; Microfabrication; Microfluidics; Organ; Organ Donor; Oxygen Therapy Care; Patients; Performance; Permeability; Physiology; Property; Research; Research Project Grants; Role; Saline; Solutions; Structure; Structure of parenchyma of lung; Surface; System; Technology; United States; Whole Blood; artificial lung; base; design; design and construction; improved; in vitro testing; lung basal segment; mortality; new technology; polydimethylsiloxane; respiratory assist; shear stress; technology development; three dimensional structure

The ultimate goal of this project is to develop artificial lung assist device technology to treat acute and chronic pulmonary failure. Chronic lung disease is the third-leading cause of death in the United States, exceeded only by heart disease and cancer. Currently there are no long-term solutions for chronic diseases such as Chronic Obstructive Pulmonary Disease (COPD) other than lung transplantation, and a severe shortage of donor organs limits this approach, leaving most patients relying on home oxygen therapy. For acute illnesses such as Adult Respiratory Distress Syndrome (ARDS), mechanical ventilation is typically required, and complications and mortality remain very high. Alternatives such as ExtraCorporeal Membrane Oxygenator (ECMO) therapy can only be used for a limited duration, require high levels of anticoagulation and involve numerous operational complexities. There is an urgent need for technological advances in artificial lung devices, including simplification and extended use of devices, a reduced need for anticoagulation, and high gas transfer rates in a compact format with low blood volumes. Here we propose an Exploratory Bioengineering Research Grant to pursue the development of technology for a bioartificial lung, based on biomimetic design principles and microfabrication technology to build scalable respiratory assist architectures capable of high levels of gas transport in a small and compact structure. Successful development of a bioartificial lung will require several critical elements, many of which have not been realized because of difficulties in mimicking natural lung physiology due to limitations in fabrication technology. The specific aims of this proposal are directed towards these elements, including the ability to design a biomimetic structure with small priming volume and high levels of gas permeability, and the establishment of an endothelialized microvascular network to support smooth blood flow without clotting in the absence of anticoagulative agents. These goals are consistent with future clinical targets including the ability to provide patients with long-term functional respiratory assist devices that do not require extensive anticoagulation and that can be enabled in a wearable or potentially implantable format. To accomplish these goals, we aim 1) To generate a biomimetic design and utilize microfabrication technology to construct an artificial lung module comprising microvascular networks and gas-permeable membranes, and 2) To establish endothelialized microfluidic network in vascular chamber and determine gas transport and blood flow coagulation properties of bioartificial lung construct.

该项目的最终目标是开发人造肺辅助设备技术来治疗急性和慢性 肺衰竭。慢性肺病是美国第三个领先的死亡原因，超过了 仅由心脏病和癌症。目前尚无针对慢性疾病的长期解决方案 慢性阻塞性肺疾病（COPD）除肺移植以外 供体器官限制了这种方法，使大多数患者依靠家庭氧疗法。对于急性疾病 例如成人呼吸窘迫综合征（ARDS），通常需要机械通气，并且 并发症和死亡率仍然很高。诸如体外膜氧合等替代品 （ECMO）治疗只能在有限的持续时间内使用，需要高水平的抗凝治疗 许多操作复杂性。迫切需要人造肺的技术进步 设备，包括设备的简化和扩展使用，抗凝需求减少以及高 以低血量的紧凑型格式的气体传输速率。在这里，我们提出探索性 生物工程研究赠款，以基于 仿生设计原理和微加工技术，以构建可扩展的呼吸辅助体系结构 能够在小型紧凑的结构中高水平的气体传输。成功发展 生物人工肺将需要几个关键元素，其中许多元素尚未实现 由于制造技术的限制，模仿天然肺部生理学的困难。具体目标 该提案针对这些元素，包括设计仿生结构的能力 较小的启动量和高水平的气体渗透性，并建立内皮化 微血管网络可在没有抗凝剂的情况下支持光滑的血流而不会凝结。 这些目标与未来的临床目标一致，包括为患者提供长期的能力 不需要广泛抗凝治疗的功能性呼吸辅助设备，可以在 可穿戴或潜在植入格式。为了实现这些目标，我们的目标是1）产生仿生 设计和利用微生物技术来构建一个包括微血管的人工肺模块 网络和气体可渗透膜，以及2）在血管中建立内皮化微流体网络 腔室并确定生物人工肺构建体的气体传输和血流凝血特性。

项目成果

Performance and scaling effects in a multilayer microfluidic extracorporeal lung oxygenation device.

• DOI: 10.1039/c2lc21156d
• 发表时间: 2012-05-07
• 期刊: Lab on a chip
• 影响因子: 6.1
• 作者: Kniazeva T;Epshteyn AA;Hsiao JC;Kim ES;Kolachalama VB;Charest JL;Borenstein JT
• 通讯作者: Borenstein JT