Biocompatibility of Implantable Renal Replacement Devices

植入式肾脏替代装置的生物相容性

基本信息

批准号：
8658431
负责人：
SHUVO ROY
金额：
$ 54.95万
依托单位：
UNIVERSITY OF CALIFORNIA, SAN FRANCISCO
依托单位国家：
美国
项目类别：
财政年份：
2012
资助国家：
美国
起止时间：
2012-05-01 至 2016-04-30
项目状态：
已结题

来源：
https://reporter.nih.gov/project-details/8658431
关键词：
Address Adsorption Affect American Anatomy Animal Experiments Animal Testing Animals Area Award Back Bioreactors Blood Blood Platelets Blood flow Cardiovascular system Cell Separation Cell Therapy Cells Characteristics Citrates Coagulation Process Defect Development Device Designs Devices Dialysis procedure Duct (organ) structure Electrolyte Balance End stage renal failure Equipment Malfunction Failure Family suidae Film Fright Future Geometry Grant Healthcare Hemodialysis Hemofiltration Hemolysis Histologic Homeostasis Human Image Implant In Vitro Kidney Kidney Failure Kidney Transplantation Length Liquid substance Locales Maps Measures Medical Device Medicare Membrane Methodology Modeling Modification Molecular Morbidity - disease rate National Institute of Biomedical Imaging and Bioengineering Organ Donor Patients Performance Permeability Pilot Projects Plasma Plasma Proteins Platelet Activation Polymers Population Preparation Prevalence Process Property Proteins Renal tubule structure Rodent Role Saline Salts Shapes Sheep Silicon Sodium Chloride Solutions Surface System Tantalum Techniques Technology Testing Thrombosis Time Toxin Transmembrane Transport Transplantation Ultrafiltration United States National Institutes of Health Variant Water Whole Blood Work base biomaterial compatibility cost design flexibility fluid flow implantable device implantation improved in vivo mortality nanopore nanoscale preclinical study pressure prototype quantum research study shear stress simulation solute success surface coating tool

项目摘要

DESCRIPTION (provided by applicant): Treatment of end stage renal disease (ESRD) patients by renal transplant is severely limited by shortage of donor organs, while dialysis is expensive, inconvenient, and confers significant morbidity and mortality. There are nearly 400,000 people in the US who rely on thrice-weekly, in-center hemodialysis, and collectively, this population consumes over $20 billion annually in Medicare-paid healthcare. The prevalence of ESRD is increasing at 5% per year, and the vast majority of patients are unlikely to ever receive a transplant. We recently embarked on the development of an implantable bioartificial kidney that combines a hemofilter constructed from silicon nanopore membranes (SNM) with a bioreactor of human renal tubule cells to mimic nephronal function. In the final envisioned implementation, blood will be filtered in the hemofilter under circulatory system pressure to remove uremic toxins, salts, small solutes, and water. The resulting ultra filtrate will then be processed by the bioreactor to selectively transport most of the salts, and water back into the blood, thereby maintaining volume homeostasis and electrolyte balance. Initial pilot studies supported by a NIH/NIBIB-sponsored Quantum Grant (1R01EB008049) allowed our team to establish fundamental concept feasibility including the development of high-performance SNM filters, anti- fouling thin-film polymer coatings, human renal tubule cell isolation and expansion techniques, and short-term implantable hemofiltration in rodents and pigs as well as wearable cell therapy in sheep. We also identified a number of critical roadblocks to successful development of implantable bioartificial kidney. Among them, a key challenge is long-term blood compatibility of the hemofilter with respect to thrombosis and membrane fouling. The proposed R01 project will attempt to better understand the blood-device interactions spanning across anatomic, histologic, and molecular length scales and their influence on hemofilter biocompatibility. More specifically, we will conduct transport characterization experiments, computational fluid dynamics (CFD) simulations, in vitro radiographic flow mapping, and in vivo animal experiments to evaluate the impact of membrane physicochemical properties on mass transfer characteristics and determine the role of fluid flow anomalies in device thrombosis. Beyond the immediate application to an implantable bioartificial kidney, this work will establish a new generalized testing methodology for implantable devices that are functionally dependent on features at both large (mm-cm) and small (nm-microns) length scales.

描述（由申请人提供）：通过肾移植对终阶段肾脏疾病（ESRD）患者的治疗受到供体器官短缺的严重限制，而透析却昂贵，不便，并且具有明显的发病率和死亡率。在美国，有近40万人依靠每周三次，中心血液透析，总体上，这一人口每年在Medicare支付的医疗保健中消耗超过200亿美元。 ESRD的患病率每年为5％，绝大多数患者不太可能接受移植。最近，我们着手开发可植入的生物人工肾脏，该肾脏结合了由硅纳米孔膜（SNM）与人类肾小管细胞的生物反应器构成的血液过滤器与模仿肾功能。在最终设想的实施中，在循环系统压力下将血液过滤，以去除尿毒症毒素，盐，小溶质和水。然后，生物反应器将处理所得的超滤液，以选择性地运输大多数盐，然后将水回到血液中，从而保持体积的体内稳态和电解质平衡。由NIH/NIBIB赞助的量子赠款支持的最初试点研究（1R01EB008049）使我们的团队能够建立基本概念的可行性，包括开发高性能SNM过滤器，抗粉状薄膜聚合物涂料，肾小管隔离和延长型单元格，以及适用于良好的良好型，以及适用于型号的良好型，以及适用于良好的良好型，以及范围内的良好型，又是强度的范围，既适合范围又有型号，又是范围内的型号，以及范围内的良好型式良好的范围，并构成型号的范围，并构成了范围内的范围，并构成了强度的范围，并构成了强度型号，并构成了强度型式的型号。绵羊。我们还确定了许多关键的障碍，以成功发展可植入的生物人工肾脏。其中，一个关键的挑战是血栓形成方面的长期血液兼容性相对于血栓形成和膜结垢。提出的R01项目将试图更好地了解跨越解剖，组织学和分子长度尺度及其对血流生物相容性的影响的血液磁发相互作用。更具体地说，我们将进行运输表征实验，计算流体动力学（CFD）模拟，体外放射学流量图和体内动物实验，以评估膜物理学特性对传质特性的影响，并确定流体流体流体在设备促进症中的作用。除了直接应用于可植入的生物人工肾脏外，这项工作还将建立一个用于植入式设备的新的广义测试方法在功能上取决于大型（MM-CM）和小（NM-Microns）长度尺度的特征。