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）：终末期肾病（ESRD）影响了超过425，000名美国人，并以每年8%的速度持续增加。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，等待移植的名单上只有25%的人能够存活足够长的时间来接受肾脏。超过30万ESRD患者的替代治疗是透析，这是昂贵的，不方便的，并赋予显着的发病率和死亡率。该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，这将消除美国每年进行的超过5000万次透析手术中的大部分。处于II期临床试验的体外肾脏辅助装置（RAD）是一种大型生物人工肾脏，将血液滤过与近端小管细胞治疗相结合，以模拟健康肾脏的许多代谢、内分泌和免疫功能。然而，成功采用RAD进行ESRD患者的常规治疗将受到其大的总体尺寸、复杂的组装和劳动密集型应用的阻碍。该量子项目将应用MEMS（微机电系统）技术和兼容的纳米技术策略，将RAD组装成一个紧凑的，可植入的，自我监测和自我调节的生物人工肾。微型植入式RAD将：（1）通过将耐用、长寿命的血液滤过器与肾小管细胞生物反应器耦合，消除一次性用品和透析液，与肾脏中发生的情况完全相同;（2）通过集成的MEMS传感器、控制电子器件和致动器自动调节细胞外液体积和清除。Quantum项目的I期将确定血液滤过器和小管细胞生物反应器的最终操作参数。对于血液滤过器，将确定膜选择性渗透的最佳孔径、机械强度和耐用性的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。第一阶段将最终在动物演示平衡过滤和重吸收的一个单一的近端人工肾单位（迷你RAD）。量子项目的第二阶段将涉及迷你RAD的规模扩大，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。将各种组件集成到植入式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 IND批准。在获得批准后，量子项目将以ESRD患者的小型化植入式RAD的“首次人体”演示结束。