Omniphobic cerebral shunt to eliminate clogging and dysfunction

全方位恐惧性脑分流以消除阻塞和功能障碍

• 批准号: 10269033
• 负责人: Saibal Bandyopadhyay
• 金额: $ 103.56万
• 依托单位: FREEFLOW MEDICAL DEVICES, LLC
• 依托单位国家: 美国
• 财政年份: 2018
• 资助国家: 美国
• 起止时间: 2018-09-01 至 2023-08-31
• 项目状态: 已结题
• 来源: https://reporter.nih.gov/project-details/10269033
• 关键词: Address; Adhesions; Adsorption; Animal Model; Astrocytes; Binding; Blood; Brain; Businesses; Catheters; Cell Culture Techniques; Cell Death; Cell-Matrix Junction; Cells; Cerebrospinal Fluid; Cerebrum; Chemicals; Chemistry; Chronic; Clinical; Clinical Trials; Communication; Cyclic GMP; Data; Development; Devices; Effectiveness; Exhibits; FDA approved; Failure; Family suidae; Fibroblasts; Fluorocarbons; Foreign Bodies; Fracture; Friction; Functional disorder; Goals; Hardness; Healthcare Systems; Hydrocephalus; Implant; In Vitro; Infection; Institutes; Lead; Licensing; Liquid substance; Manufacturer Name; Marketing; Medical; Medical Device; Microglia; Modeling; Modification; Neuroglia; Neurologic; Neurologic Deficit; Obstruction; Operative Surgical Procedures; Oryctolagus cuniculus; Outcome; Patient Care; Patient-Focused Outcomes; Patients; Phase; Physiological; Polymers; Procedures; Process; Production; Proteins; Quality of life; Rattus; Reporting; Research; Research Contracts; Resistance; Safety; Secondary to; Shunt Device; Small Business Technology Transfer Research; Standardization; Structure of choroid plexus; Surface; Surgical sutures; System; Technology; Testing; Time; Tissues; Universities; Ventricular; Washington; Work; base; biobank; biomaterial compatibility; cell type; cerebrospinal fluid flow; clinically relevant; commercialization; cost; efficacy testing; flexibility; implantable device; improved; in vivo; innovation; innovative technologies; manufacturing process; novel; pathogen; phase 3 study; physical property; prevent; prototype; response; subcutaneous; systemic toxicity

PROJECT SUMMARY Hydrocephalus causes long term neurological problems and patient suffering. Current treatments, most of which involve surgical diversion of cerebrospinal fluid (CSF) with shunt catheters, fail at an alarming rate. Approximately 98% of all shunts fail within 10 years, and this failure rate is the dominant contributor to the $2 billion-per-year cost that hydrocephalus incurs on our health care system. The most common causes of shunt failure are clogging and infections; clogging is associated with glia cell attachment, which promotes the attachment of other cells and tissues, finally inhibiting the CSF flow. Therefore, directly inhibiting cell attachment on catheter surfaces should ameliorate shunt obstruction. During our phase I proposal, we conducted a proof of concept study to evaluate the merit of tethered liquid perfluorocarbon (TLP) coating to ameliorate shunt clogging. Importantly, previous work demonstrated that TLP-coated medical devices exhibit reduced protein adsorption, successfully resist adherent fibroblast and glial cell attachment in vitro and in vivo, repel blood and its protein constituents, reduce foreign body encapsulation, and can inhibit adsorption of a broad class of infectious pathogens onto surfaces. During our phase I research, we improved the coating process for hydrocephalus shunt catheters and demonstrated that the TLP coating could dramatically inhibit glia cell attachment and therefore mechanistically minimize shunt clogging during in vivo studies. We also established that the coating is biocompatible and could sustain long term physiological flow. The objectives of Phase II research is to commercialize the shunt catheter by good manufacturing practice (GMP), as required by FDA, and demonstrate the efficacy of TLP-coated shunt catheters by implanting the device in a hydrocephalus-induced animal model. This will be achieved by manufacturing the TLP so it is ready for FDA and clinical trials, testing efficacy in a hydrocephalic animal model, and testing biocompatibility in a GLP lab. We have already established communications with a major shunt manufacturer. Upon successful completion of these studies and after obtaining FDA approval, FFMD will license the coating technology for further clinical trials and marketing. The successful development and commercialization of this highly innovative technology will provide a paradigm shift in the treatment of hydrocephalus by focusing on mechanisms that reduce cell and tissue adhesion on ventricular catheters.

项目摘要 脑积水会导致长期的神经系统问题和患者痛苦。目前的治疗，大多数 其涉及用分流导管对脑脊髓液（CSF）进行外科分流，以惊人的速度失败。 大约98%的所有分流器在10年内失效，并且该失效率是导致2010年2美元 脑积水每年给我们的医疗系统带来的成本高达10亿美元。分流最常见的原因 失败是堵塞和感染;堵塞与胶质细胞附着有关，这促进了细胞的生长。 其他细胞和组织的附着，最终抑制CSF流动。因此，直接抑制细胞 在导管表面上的附着应改善分流阻塞。在我们的第一阶段提案中，我们 进行了一项概念验证研究，以评估系留液体全氟化碳（TLP）涂层的优点， 改善分流器堵塞。重要的是，以前的工作表明，TLP涂层的医疗器械表现出 减少蛋白质吸附，在体外和体内成功地抵抗粘附的成纤维细胞和神经胶质细胞附着， 排斥血液及其蛋白质成分，减少异物包裹，并可抑制 广泛种类的传染性病原体到表面上。在第一阶段的研究中，我们改进了涂层 脑积水分流导管的工艺，并证明了TLP涂层可以显著抑制 神经胶质细胞附着并因此在体内研究期间机械地最小化分流器堵塞。我们也 确定涂层是生物相容的，并且可以维持长期的生理流动。 II期研究的目的是通过良好生产规范将分流导管商业化 (GMP)，并通过植入 装置在脑积水诱导的动物模型中。这将通过制造TLP来实现，以便其准备就绪 对于FDA和临床试验，在脑积水动物模型中测试功效，并在 GLP实验室。我们已经与一家主要分流器制造商建立了联系。一旦成功 完成这些研究并获得FDA批准后，FFMD将授权涂层技术用于 进一步的临床试验和营销。这一高度商业化的成功开发 创新技术将提供脑积水治疗的范式转变， 减少细胞和组织粘附在心室导管上的机制。