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: 7343505
• 负责人: SHUVO ROY
• 金额: $ 112.25万
• 依托单位: CLEVELAND CLINIC LERNER COM-CWRU
• 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 2008-08-31
• 项目状态: 已结题
• 来源: https://reporter.nih.gov/project-details/7343505
• 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; 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）：末期肾脏疾病（ESRD）影响超过42.5万名美国人，并且每年8％的患病率继续增加。肾脏移植是选择的治疗方法，受到供体器官稀缺的严重限制，因此，在等待名单上只有25％的移植存活时间足以接受肾脏。超过30万例ESRD患者的替代治疗方法是透析，这是昂贵，不便，并且赋予了明显的发病率和死亡率。这个量子项目最终将提供一个可植入的，自我调节的生物人工肾脏，该肾脏将消除美国每年在美国执行的> 5000万个透析手术中的大多数。在II期临床试验中的体外肾脏辅助装置（RAD）是一种大型生物人工肾脏，将血液过滤与近端小管细胞疗法结合在一起，模仿健康肾脏的许多代谢，内分泌和免疫学功能。但是，成功采用RAD的常规治疗ESRD患者将受到其较大的整体规模，复杂组装和劳动力密集型应用的阻碍。该量子项目将采用MEM（微电机电系统）技术和兼容的纳米技术策略，以将RAD微型化成紧凑，可植入，自我监控和自我调节的生物人工肾脏。微型植入式RAD将：（1）通过将耐用的长寿命血过滤器与肾小管细胞的生物反应器耦合，消除一次性物品并透析，就像肾脏中一样； （2）通过集成的MEMS传感器，控制电子和执行器自我调节的细胞外流体体积和清除率。量子项目的第一阶段将建立血液过滤器和小管细胞生物反应器的最终操作参数。对于血液滤池，将确定膜允许性的最佳孔径，机械强度和稳健性的孔布局以及用于血液生物相容性的表面涂料。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。第一阶段将在动物示范中通过单个近端人工肾单位（Mini-Rad）进行平衡过滤和重新吸收。量子项目的第二阶段将涉及对迷你RAD的扩展，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。各种组件将集成到可植入的RAD中，以进行演示，以在动物模型中建立总体可行性。如果成功，将寻求FDA IND批准。在获得批准后，量子项目将以ESRD患者的微型植入式RAD的“首次人类”演示终止。