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Fiber design and assessment for development of a novel biomimetic medical device

用于开发新型仿生医疗设备的纤维设计和评估

基本信息

批准号：
8979404
负责人：
Christopher Pino
金额：
$ 32.38万
依托单位：
INNOVATIVE BIOTHERAPIES, INC.
依托单位国家：
美国
项目类别：
财政年份：
2015
资助国家：
美国
起止时间：
2015-08-01 至 2017-03-31
项目状态：
已结题

来源：
https://reporter.nih.gov/project-details/8979404
关键词：
Abattoirs Acute Disease Acute Renal Failure with Renal Papillary Necrosis Adherence Adhesions Adult Advanced Development Animal Disease Models Animal Model Anticoagulation Antineutrophil Cytoplasmic Antibodies Applications Grants Biological Biological Response Modifier Therapy Biomimetics Biotechnology Blood Blood Cells Blood Volume Blood flow Caliber Catheters Cattle Characteristics Child Childhood Chronic Disease Citrates Clinic Clinical Clinical Research Clinical Trials Congestive Heart Failure Critical Illness Data Dermatomyositis Development Devices Dialysis procedure Disease Electron Beam Equilibrium Ethylene Oxide Etiology Evaluation Excision FDA approved Face Family suidae Feedback Fiber Functional disorder Future Generations Goals Government Health Hemodialysis Hemofiltration Human Immune system Inflammation Inflammatory Injury Intracranial Hemorrhages Kidney Kidney Diseases Kinetics Leukocytes Lipids Marketing Medical Device Membrane Methodology Methods Mission Modeling Organ failure Outcome Outpatients Patients Persons Phase Polymers Process Production Property Rare Diseases Regenerative Medicine Relative (related person)Reperfusion Injury Research Safety Septic Shock Solutions Sterilization Surface Syndrome Technology Testing Therapeutic Equivalency Time Translations Vasculitis Venous Virginia Wetting Agents Work base clinical efficacy design hemodynamics improved innovation manufacturing process meetings mortality multiorgan injury novel pediatric patients polysulphone pre-clinical public health relevance success

项目摘要

DESCRIPTION (provided by applicant): The Selective Cytopheretic Device (SCD) is an extracorporeal medical device targeted to treat patients with inflammatory disease indications. As patient blood passes through the SCD, it comes in contact with the hemocompatible fibers inside the SCD. These fibers are capable of immunomodulatory interactions with the patient's over-active white blood cells (activated leukocytes). The SCD has been used in three human clinical studies to date, with positive clinical outcomes for critically ill adult patients with acte kidney injury (AKI) and multiorgan dysfunction (MOD). Long term objective: to develop a process to manufacture fibers with an outer diameter (OD) = 140 µm, for use in a second generation SCD (SCD2) with low blood fill volumes to enable the treatment of pediatric patients and critically ill adult patients with blood volume removal re- strictions due to potential hemodynamic instability, as well as treatment in out-patient clinics via peripherally inserted central catheter (PICC) access, which require low blood flow rates. Fibers within the current SCD are made of polysulfone (PSu) and have an OD of 280 µm. Current technology in hemodialysis fiber manufacturing is restricted to fabricating fibers with OD of between 280 to 600 µm. These fibers are far too large to be used in the SCD2, which would cause the blood priming volumes to be high, and therefore not safe for pediatric patients and critically ill patiens. In order to make the blood fill volumes <50 mL for these patients, the fibers must be made =140 µm. A lab at Virginia Tech will be used to manufacture fibers of the required specifications for the SCD2 device, which will enable the rapid development of the fiber making process toward clinical translation for the SCD2 to save severely ill patients' lives. In this project, the way in which the SCD works, called the mechanism of action (MoA) will be explored by specifically looking at how white blood cells (WBC) interact with the fibers in the device (Specific Aim 1) by using fresh cow blood from a local slaughterhouse. Production methodology for =140 µm OD fibers will be developed by finding just the right balance of polymers to change the surface of the fibers for the best interaction with WBC, also tested with cow blood (Specific Aim 2). The fibers produced in Aim 2 will be sterilized by different methods in Specific Aim 3, and will be tested with cow blood. These optimized, sterilized fibers would be ready for use in a medical device to test in a preclinical large animal model, to prove efficacy. If they are safe and work well, then the finalized devices could be used in a human clinical trial. Health Related Impact: The data generated from this proposal will advance the development of a critical manufacturing process for fabrica- tion of PSu fibers needed to produce SCD2. It will also provide preclinical data for inclusion of regulatory sub- missions to apply for IDE approval from the FDA to initiate clinical trials for the evaluation of SCD2 therapy in both acute and chronic disease indications, including orphan diseases: anti-neutrophil cytoplasmic antibody (ANCA) vasculitis, dermatomyositis, Guillian-Barre Syndrome (GBS), and pediatric AKI.

描述（由申请人提供）：选择性细胞分离装置（SCD）是一种体外医疗装置，旨在治疗患有炎症性疾病的患者。当患者血液流经 SCD 时，它会与 SCD 内的血液相容性纤维接触。这些纤维能够与患者过度活跃的白细胞（活化的白细胞）进行免疫调节相互作用。迄今为止，SCD 已用于三项人体临床研究，对患有急性肾损伤 (AKI) 和多器官功能障碍 (MOD) 的危重成人患者取得了积极的临床结果。长期目标：开发一种制造外径（OD）= 140 µm的纤维的工艺，用于低血液填充量的第二代SCD（SCD2），以便能够治疗由于潜在的血流动力学不稳定而导致血容量清除受限的儿科患者和危重成人患者，以及通过外周插入中心静脉导管（PICC）通路在门诊诊所进行治疗，这需要低血容量血流量。当前 SCD 中的光纤由聚砜 (PSu) 制成，外径为 280 µm。目前的血液透析纤维制造技术仅限于制造 OD 在 280 至 600 µm 之间的纤维。这些纤维太大，无法在 SCD2 中使用，这会导致血液预充量过高，因此对于儿科患者和危重患者来说不安全。为了使这些患者的血液填充量<50 mL，纤维必须制成=140 µm。弗吉尼亚理工大学的一个实验室将用于制造符合 SCD2 设备所需规格的纤维，这将使纤维制造工艺快速发展，实现 SCD2 的临床转化，从而挽救重症患者的生命。在这个项目中，采用的方式是 SCD 的工作原理称为作用机制 (MoA)，将通过使用当地屠宰场的新鲜牛血专门观察白细胞 (WBC) 与装置中纤维的相互作用（具体目标 1）来探索。 =140 µm OD 纤维的生产方法将通过找到聚合物的正确平衡来开发，以改变纤维表面，以获得与 WBC 的最佳相互作用，也用牛血进行了测试（具体目标 2）。目标2中生产的纤维将在具体目标3中通过不同的方法进行灭菌，并用牛血进行测试。这些优化的灭菌纤维可用于医疗设备，在临床前大型动物模型中进行测试，以证明功效。如果它们安全且工作良好，那么最终的设备可以用于人体临床试验。健康相关影响：该提案生成的数据将推动生产 SCD2 所需 PSu 纤维关键制造工艺的开发。它还将提供临床前数据，以纳入监管提交申请 FDA 的 IDE 批准，以启动评估 SCD2 疗法在急性和慢性疾病适应症中的临床试验，包括孤儿疾病：抗中性粒细胞胞质抗体（ANCA）血管炎、皮肌炎、吉利安-巴利综合征（GBS）和儿科疾病急性肾损伤。