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) 影响着超过 425,000 名美国人，并且患病率继续以每年 8% 的速度增加。肾脏移植作为首选治疗方法，受到供体器官稀缺的严重限制，因此等待移植的名单上只有 25% 的患者能够存活足够长的时间来接受肾脏。超过 300,000 名 ESRD 患者的替代治疗方法是透析，但这种方法价格昂贵、不方便，并且发病率和死亡率很高。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 万例透析手术中的大部分。处于 II 期临床试验的体外肾辅助装置 (RAD) 是一种大型生物人工肾，它将血液滤过与近端小管细胞疗法相结合，以模仿健康肾脏的许多代谢、内分泌和免疫功能。然而，RAD 的整体尺寸大、组装复杂和劳动密集型的应用将阻碍其成功采用 RAD 进行 ESRD 患者的常规治疗。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小型化为紧凑的、可植入的、自我监控和自我调节的生物人工肾。小型化植入式 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耦合，消除一次性用品和透析液，就像肾脏中发生的情况一样； (2) 通过集成 MEMS 传感器、控制电子设备和执行器自我调节细胞外液体积和间隙。量子项目的第一阶段将确定血滤器和肾小管细胞生物反应器的最终操作参数。对于血滤器，将建立膜渗透选择性的最佳孔径、机械强度和稳健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，将确定最大肾小管细胞运输的培养条件。第一阶段将通过动物演示单个近端人工肾单位（mini-RAD）的平衡过滤和重吸收来达到高潮。量子项目的第二阶段将涉及迷你 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。各种组件将被集成到可植入的 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。获得批准后，量子项目将终止，并在终末期肾病患者身上进行小型化植入式 RAD 的“首次人体”演示。