Omniphobic Cerebral Shunt to Eliminate Clogging and Dysfunction

项目总结 脑积水会导致长期的神经问题和患者痛苦。目前的治疗方法，大多数 包括使用分流导管进行脑脊液分流的手术，以惊人的速度失败。 大约98%的分流装置在10年内失败，这一故障率是2美元的主要贡献者 脑积水每年给我们的医疗保健系统带来的数十亿美元的成本。分流的最常见原因 失败是堵塞和感染；堵塞与胶质细胞附着有关，这会促进 附着其他细胞和组织，最终抑制脑脊液流动。因此，直接抑制细胞 导管表面的附着物应能改善分流阻塞。在我们的第一阶段提案中，我们 进行概念验证研究，以评估系留液体全氟碳(TLP)涂层的优点 改善分流堵塞。重要的是，以前的工作表明，TLP涂层的医疗器械展示了 减少蛋白质吸附，在体外和体内成功抵抗黏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，并能抑制对a的吸附 广泛的传染性病原体在表面上。在我们的第一阶段研究中，我们改进了涂层 用于脑积水分流导管的工艺，并证明TLP涂层可以显著地抑制 胶质细胞附着，因此在体内研究期间机械地最大限度地减少分流堵塞。我们也 确定涂层具有生物相容性，并能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)，并通过将TLP涂层的分流导管植入 在脑积水诱导的动物模型中的装置。这将通过制造TLP以使其准备就绪来实现 对于FDA和临床试验，在脑积水动物模型中测试疗效，在 普洛斯实验室。我们已经与一家主要的分流器制造商建立了联系。成功后 完成这些研究并获得FDA批准后，FFMD将许可涂层技术用于 进一步的临床试验和营销。它的成功开发和商业化的高度 创新技术将为脑积水的治疗提供范式转变，其重点是 减少细胞和组织在脑室导管上黏附的机制。

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.