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（由适用提供）：选择性细胞处理装置（SCD）是一种用于治疗患有炎症性疾病适应症患者的体外医疗装置。当患者血液通过SCD时，它与SCD内的血流纤维接触。这些纤维能够与患者过度活跃的白细胞（活化的白细胞）进行免疫调节性相互作用。迄今为止，SCD已在三项人类临床研究中使用，患有ACTE肾脏损伤（AKI）和多器官功能障碍（MOD）的成年成年患者的临床结果呈阳性。 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 requires血流量低。当前SCD中的纤维由多硫酮（PSU）制成，OD为280 µm。血液透析纤维生产中的当前技术仅限于制造280至600 µm的OD的纤维。这些纤维太大了，无法在SCD2中使用，这会导致血液启动量很高，因此对于小儿患者和重症患者而言，不安全。为了使这些患者的血液填充量<50 mL，必须制成纤维= 140 µm。 Virginia Tech的实验室将用于制造SCD2设备所需规范的纤维，这将使纤维制造过程的快速开发用于SCD2的临床翻译，以挽救严重患者的生命。在这个项目中， SCD的作用，称为“作用机理”（MOA），将通过专门研究白细胞（WBC）如何通过使用当地屠宰场的新鲜牛血与设备中的纤维相互作用（特定目标1）来探索。通过发现聚合物的适当平衡以改变纤维表面以与WBC进行最佳相互作用，还可以通过牛血液进行测试，从而开发出= 140 µm OD纤维的生产方法（特定的AIM 2）。在AIM 2中生产的纤维将通过特定AIM 3中的不同方法对其进行消毒，并将用牛血进行测试。这些优化的，灭菌的纤维可以在医疗装置中使用，以在临床前大型动物模型中进行测试，以证明有效。如果它们安全且运行良好，则可以在人类的临床试验中使用最终设备。与健康相关的影响：该提案产生的数据将推动开发生产SCD2所需的PSU纤维的关键制造过程。 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, dermatomomyositis, Guillian-Barre Syndrome (GBS), and小儿Aki。