Biomimetic Design and Construction of an Artificial Lung

人工肺的仿生设计与构造

• 批准号: 8033302
• 负责人: Jeffrey T. Borenstein
• 金额: $ 26.07万
• 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 2012-11-30
• 项目状态: 已结题
• 来源: https://reporter.nih.gov/project-details/8033302
• 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

DESCRIPTION (provided by applicant): 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. PUBLIC HEALTH RELEVANCE: The ultimate goal of this project is to develop a medical device capable of oxygenating the blood of patients suffering from acute and chronic lung diseases and cardiopulmonary failure. Current technologies cannot be used for more than one month, require high levels of anti-clotting agents, and often damage sensitive lung tissues. This new technology will mimic the structure and function of natural, healthy lungs and provide a long- term treatment for patients suffering from acute lung injury, chronic obstructive pulmonary disease, and other conditions that cause hypoxia.

描述（由申请人提供）：本项目的最终目标是开发人工肺辅助装置技术，用于治疗急性和慢性肺衰竭。慢性肺病是美国第三大死亡原因，仅次于心脏病和癌症。目前，除了肺移植之外，对于慢性阻塞性肺病（COPD）等慢性病还没有长期的解决方案，而供体器官的严重短缺限制了这种方法，使大多数患者依赖家庭氧气治疗。对于急性疾病，如成人呼吸窘迫综合征（ARDS），通常需要机械通气，并发症和死亡率仍然非常高。替代疗法，如皮质外膜氧合器（ECMO）治疗，只能在有限的时间内使用，需要高水平的抗凝治疗，并涉及许多操作复杂性。迫切需要人工肺装置的技术进步，包括装置的简化和延长使用，减少对抗凝剂的需求，以及具有低血量的紧凑形式的高气体传输速率。在这里，我们提出了一项探索性生物工程研究资助，以基于仿生设计原理和微细加工技术来开发生物人工肺技术，以构建能够在小型紧凑结构中实现高水平气体输送的可扩展呼吸辅助架构。生物人工肺的成功开发将需要几个关键要素，其中许多要素尚未实现，因为由于制造技术的限制，难以模仿天然肺生理学。该提案的具体目标是针对这些元素，包括设计具有小预充体积和高水平气体渗透性的仿生结构的能力，以及建立内皮化微血管网络以支持在不存在抗凝剂的情况下无凝血的平稳血流。这些目标与未来的临床目标一致，包括能够为患者提供长期功能性呼吸辅助设备，这些设备不需要大量抗凝，并且可以以可穿戴或潜在植入的形式启用。为了实现这些目标，我们的目标是：1）产生仿生设计，并利用微制造技术构建包括微血管网络和透气膜的人工肺模块; 2）在血管腔中建立内皮化的微流体网络，并确定生物人工肺构建物的气体传输和血流凝固特性。 公共卫生相关性：该项目的最终目标是开发一种能够为患有急性和慢性肺部疾病以及心肺功能衰竭的患者的血液充氧的医疗器械。目前的技术不能使用超过一个月，需要高水平的抗凝剂，并经常损害敏感的肺组织。这项新技术将模仿自然健康肺部的结构和功能，为患有急性肺损伤、慢性阻塞性肺病和其他导致缺氧的疾病的患者提供长期治疗。