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: 7499663
• 负责人: SHUVO ROY
• 金额: $ 100.43万
• 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 2010-08-31
• 项目状态: 已结题
• 来源: https://reporter.nih.gov/project-details/7499663
• 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 Therapy; Cells; Characteristics; Charge; Clinical; Clinical Trials; Compatible; Complement Activation; Complex; Condition; 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 Diseases; 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; Physical Dialysis; Physiological; Polyethylene Glycols; Polymers; Prevalence; Proteins; Protocols documentation; Rate; Renal Replacement Therapy; Renal tubule structure; Rodent Model; Salts; Serum Albumin; Silicon; Sodium; Staging; Surface; System; Techniques; Technology; Testing; Toxin; Transplantation; Ultrafiltration; United States Food and Drug Administration; Urea; Validation; Waiting Lists; Water; absorption; biomaterial compatibility; concept; dacron; design; implantation; in vivo; miniaturize; monolayer; mortality; nanoimprint lithography; nanopore; pressure; prototype; quantum; scale up; self assembly; sensor; size; 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）影响超过425,000名美国人，并以每年8%的速度继续增加患病率。肾移植是一种治疗选择，但由于供体器官的稀缺而受到严重限制，因此等待移植的人中只有25%的人能够存活到接受肾脏移植。超过30万ESRD患者的替代治疗是透析，这是昂贵的，不方便的，并带来显著的发病率和死亡率。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脏，这将消除美国每年约5000万例透析手术中的大部分。体外肾辅助装置（RAD）是一种大型生物人工肾脏，它将血液过滤和近端小管细胞治疗结合起来，模仿健康肾脏的许多代谢、内分泌和免疫功能。然而，由于其整体尺寸大、组装复杂、应用劳动密集型，将RAD成功应用于ESRD患者的常规治疗将受到阻碍。这个量子项目将应用MEMS（微机电系统）技术和兼容的纳米技术策略，将RAD小型化成一个紧凑的、可植入的、自我监测和自我调节的生物人工肾脏。微型植入式RAD将：(1)通过将耐用、长寿命的血液过滤器与肾小管细胞生物反应器相结合，消除一次性和透析，就像肾脏一样；(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体积和间隙。量子项目的第一阶段将确定血液过滤器和小管细胞生物反应器的最终操作参数。对于血液过滤器，将建立膜透选择性的最佳孔径，机械强度和坚固性的最佳孔布局，以及血液生物相容性的表面涂层。对于细胞生物反应器，将确定最大小管细胞转运的培养条件。第一阶段将在动物实验中达到高潮，通过一个近端人工肾元（mini-RAD）平衡过滤和重吸收。量子项目的第二阶段将涉及mini-RAD的放大、体积稳态策略的优化、代谢平衡的测试以及包装和电子产品的开发。各种组件将被整合到一个植入式RAD中进行演示，以在动物模型中建立整体可行性。如果成功，将寻求FDA的IND批准。在获得批准后，量子项目将在ESRD患者身上进行“首次人体”微型植入式RAD演示。