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 脑积水会导致长期神经问题和患者痛苦。当前治疗，大多数 这涉及脑脊液（CSF）用分流导管的手术转移，以惊人的速度失败。 大约有98％的分流器在10年内失败，此故障率是$ 2的主要贡献者 脑积水每年的成本涉及我们的医疗保健系统。分流的最常见原因 失败是堵塞和感染；堵塞与神经胶质细胞的附着有关，这促进了 其他细胞和组织的附着，最后抑制CSF流动。因此，直接抑制细胞 导管表面的附着应减轻分流阻塞。在我们的阶段我的建议中，我们 进行了概念验证研究，以评估束缚液体全氟碳（TLP）涂层的优点 改善分流堵塞。重要的是，以前的工作表明TLP涂层的医疗设备展出 蛋白质吸附降低，在体外和体内成功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，减少异物的封装，并可以抑制A的吸附 大量的感染性病原体在表面上。在我们的研究期间，我们改善了涂料 脑积水管导管的过程，并证明TLP涂层可以极大地抑制 胶质细胞的附着，因此在体内研究过程中机械地将分流堵塞最小化。我们也是 确定涂层是生物相容性的，可以维持长期的生理流动。 第二阶段研究的目标是通过良好的制造实践将分流导管商业化 （GMP），根据FDA的要求，并通过植入TLP涂层的分流导管的功效 脑积水诱导的动物模型中的装置。这将通过制造TLP来实现，以便它准备就绪 对于FDA和临床试验，在脑积极动物模型中测试功效，并测试生物相容性 GLP实验室。我们已经与主要分流制造商建立了通信。成功 完成这些研究并获得FDA批准后，FFMD将许可涂料技术 进一步的临床试验和营销。这一高度的成功发展和商业化 创新技术将通过专注于 减少心室导管上细胞和组织粘附的机制。