Miniaturized Implantable Renal Assist Device for Total Renal Replacement Therapy

用于全肾脏替代治疗的微型植入式肾脏辅助装置

• 批准号: 7681240
• 负责人: SHUVO ROY
• 金额: $ 100.29万
• 依托单位: UNIVERSITY OF CALIFORNIA, SAN FRANCISCO
• 依托单位国家: 美国
• 财政年份: 2007
• 资助国家: 美国
• 起止时间: 2007-09-30 至 2011-08-31
• 项目状态: 已结题
• 来源: https://reporter.nih.gov/project-details/7681240
• 关键词: Active Biological Transport; Acute Kidney Failure; Adhesions; Adoption; Adsorption; Affect; Albumins; American; Angiotensin II; Animal Model; Animals; Area; Biocompatible; Biomimetics; Bioreactors; Blood; Blood Platelets; Catecholamines; Cell Culture Techniques; Cell Therapy; Cells; Characteristics; Charge; Clinical; Clinical Trials; Complement Activation; Complex; Coupling; Creatinine; Critical Care; Dependence; Development; Devices; Dialysis procedure; Electrolyte Balance; Electrolytes; Electronics; End stage renal failure; Endocrine; Environment; Epithelial Cells; Equilibrium; Excretory function; Extracellular Fluid; Fiber; Film; Filtration; Finite Element Analysis; Goals; Harvest; Hemofiltration; Homeostasis; Housing; Human; Infusion Pumps; Inulin; Kidney; Kidney Transplantation; Life; Measures; Mechanics; Medical; Membrane; Metabolic; Modeling; Modification; Molecular Weight; Monitor; Morbidity - disease rate; Nanotechnology; Nephrons; Oligosaccharides; Operative Surgical Procedures; Organ Donor; Patients; Permeability; Phase; Phase II Clinical Trials; Phosphorus; Physiological; Polyethylene Glycols; Polymers; Prevalence; Proteins; Protocols documentation; Renal Replacement Therapy; Renal tubule structure; Rodent Model; Salts; Serum Albumin; Silicon; Sodium; Surface; System; Techniques; Technology; Testing; Toxin; Transplantation; Ultrafiltration; Urea; Validation; Waiting Lists; Water; absorption; alternative treatment; biomaterial compatibility; dacron; design; implantation; in vivo; miniaturize; monolayer; mortality; nanoimprint lithography; nanopore; pressure; prototype; quantum; scale up; self assembly; sensor; solute; surface coating; surfactant; tissue culture

DESCRIPTION (provided by applicant): End stage renal disease (ESRD) affects over 425,000 Americans and continues to increase in prevalence at 8% annually. Kidney transplant, the treatment of choice, is severely limited by scarcity of donor organs such that only 25% on the waiting list for a transplant survive long enough to receive a kidney. The alternative treatment for over 300,000 ESRD patients is dialysis, which is expensive, inconvenient, and confers significant morbidity and mortality. This Quantum Project will ultimately deliver an implantable, self-regulating, bioartificial kidney that will eliminate majority of the >50 million dialysis procedures performed annually in the US. The extracorporeal Renal Assist Device (RAD), which is in Phase II clinical trials, is a large bioartificial kidney that combines hemofiltration with proximal tubule cell therapy to mimic many of the metabolic, endocrine, and immunological functions of a healthy kidney. However, successful adoption of the RAD for routine treatment of ESRD patients will be hampered by its large overall size, complex assembly, and labor-intensive application. This Quantum Project will apply MEMS (microelectromechanical systems) technology and compatible nanotechnology strategies to miniaturize the RAD into a compact, implantable, self-monitoring and self-regulating bioartificial kidney. The miniaturized implantable RAD will: (1) eliminate disposables and dialysate by coupling a durable, long-life hemofilter with a bioreactor of renal tubule cells, exactly as happens in the kidney; and (2) self-regulate extracellular fluid volume and clearance through integrated MEMS sensors, control electronics, and actuators. Phase I of the Quantum Project will establish the final operational parameters for the hemofilter and the tubule cell bioreactor. For the hemofilter, the optimum pore size for membrane permselectivity, pore layout for mechanical strength and robustness, and surface coatings for blood biocompatibility will be established. For the cell bioreactor, culture conditions for maximum tubule cell transport will be determined. Phase I will culminate in an animal demonstration of balanced filtration and re-absorption by a single proximal artificial nephron (mini-RAD). Phase II of the Quantum Project will involve scale-up of the mini-RAD, optimization of volume homeostasis strategies, testing of metabolic balance, and development of packaging and electronics. The various components will be integrated into an implantable RAD for demonstration to establish overall feasibility in an animal model. If successful, a FDA IND approval will be sought. After approval is received, the Quantum Project will terminate with a "first-in-human" demonstration of the miniaturized implantable RAD in an ESRD patient.

描述(由申请人提供)：终末期肾病(ESRD)影响着超过425,000名美国人，并以每年8%的速度继续增加。肾移植是首选的治疗方法，由于供体器官稀缺，移植受到严重限制，以至于在等待移植的名单上只有25%的人存活了足够长的时间来接受肾脏移植。对于超过300,000名终末期肾病患者的替代治疗是透析，这是昂贵、不方便的，并且具有显著的发病率和死亡率。这个量子项目最终将提供一种可植入的、自我调节的生物人工肾，它将消除美国每年进行的5000万次透析程序中的大部分。处于第二阶段临床试验的体外肾辅助装置(RAD)是一种大型生物人工肾脏，它结合了血液滤过和近端小管细胞治疗，以模拟健康肾脏的许多代谢、内分泌和免疫功能。然而，RAD的总体尺寸大、装配复杂、劳动密集型应用将阻碍RAD成功地应用于ESRD患者的常规治疗。这个量子项目将应用MEMS(微型机电系统)技术和兼容的纳米技术战略，将RAD微型化，成为一个紧凑、可植入、自我监测和自我调节的生物人工肾。这种小型化的植入式RAD将：(1)通过将耐用、长寿命的血液过滤器与肾小管细胞的生物反应器结合起来，消除一次性用品和透析液，与肾脏中的情况完全相同；(2)通过集成的MEMS传感器、控制电子设备和执行器，自我调节细胞外液的量和清除。量子计划的第一阶段将确定血液过滤器和管状细胞生物反应器的最终运行参数。对于血液过滤器，将建立用于膜渗透选择性的最佳孔径、用于机械强度和坚固性的孔布局以及用于血液生物相容性的表面涂层。对于细胞生物反应器，将确定最大限度地传输小管细胞的培养条件。第一阶段将在动物演示中达到高潮，即单个近端人工肾单位(mini-RAD)的平衡过滤和重吸收。量子计划的第二阶段将包括扩大迷你RAD的规模，优化容量动态平衡策略，测试代谢平衡，以及开发包装和电子产品。各种组件将被集成到可植入的RAD中进行演示，以在动物模型中建立总体可行性。如果成功，将寻求FDA IND的批准。在获得批准后，Quantum项目将以在ESRD患者身上进行微型可植入RAD的“人类第一”演示而终止。

项目成果

Biomolecular transport through hemofiltration membranes.

• DOI: 10.1007/s10439-009-9642-0
• 发表时间: 2009-04
• 期刊: ANNALS OF BIOMEDICAL ENGINEERING
• 影响因子: 3.8
• 作者: Conlisk, A. T.;Datta, Subhra;Fissell, William H.;Roy, Shuvo
• 通讯作者: Roy, Shuvo

Imaging assessment of a portable hemodialysis device: detection of possible failure modes and monitoring of functional performance.

• DOI: 10.7243/2052-6962-2-2
• 发表时间: 2014-03-27
• 期刊: Medical instrumentation (Luton, England)
• 作者: Olorunsola OG;Kim SH;Chang R;Kuo YC;Hetts SW;Heller A;Kant R;Saeed M;Fissell WH;Roy S;Wilson MW
• 通讯作者: Wilson MW

Effect of Divalent Ions on Electroosmotic Flow in Microchannels.

• DOI: 10.1016/j.mechrescom.2008.07.006
• 发表时间: 2009-01
• 期刊: Mechanics research communications
• 影响因子: 2.4
• 作者: Datta S;Conlisk AT;Li HF;Yoda M
• 通讯作者: Yoda M

A microfluidic bioreactor with integrated transepithelial electrical resistance (TEER) measurement electrodes for evaluation of renal epithelial cells.

• DOI: 10.1002/bit.22835
• 发表时间: 2010-11-01
• 期刊: BIOTECHNOLOGY AND BIOENGINEERING
• 影响因子: 3.8
• 作者: Ferrell, Nicholas;Desai, Ravi R.;Fleischman, Aaron J.;Roy, Shuvo;Humes, H. David;Fissell, William H.
• 通讯作者: Fissell, William H.

First Implantation of Silicon Nanopore Membrane Hemofilters.

• DOI: 10.1097/mat.0000000000000367
• 发表时间: 2016-07
• 期刊: ASAIO journal (American Society for Artificial Internal Organs : 1992)
• 作者: Kensinger C;Karp S;Kant R;Chui BW;Goldman K;Yeager T;Gould ER;Buck A;Laneve DC;Groszek JJ;Roy S;Fissell WH
• 通讯作者: Fissell WH