Ultra-low attachment coatings to maintain CSF shunt patency

项目摘要 超过700，000美国人需要脑脊液（CSF）分流，以减轻多余的脑脊液 然而，>30%的这些分流器在2年内失效，需要多次翻修手术。共同 脑脊液分流失败的原因包括无菌性堵塞、感染和机械故障。无菌堵塞是 对大多数故障负责，但在市场上未得到解决。硅胶钝化 针对细胞和组织粘附以及初始蛋白质沉积和变性的分流是有吸引力的 减少栓塞和组织长入的策略是翻修手术频率的基础， 脑积水患者。该提案审查了一种用于硅树脂分流器的新型涂层， 用于类器官的附着多孔板。我们建议开发一种生物相容的表面改性 与其他硅树脂表面改性方法不同， 永久与有机硅和抗疏水性恢复，一个常见的情况下，小硅 低聚物通过涂层迁移，再次用硅酮覆盖表面。此外，涂层将抵抗 >99%的CNS细胞和组织的细胞粘附。为了验证技术并建立原理证明， 将评价涂层分流器头端与小胶质细胞和星形胶质细胞、脑组织碎片的粘附， 脉络丛组织片在脑积水分流导管生物反应器系统中模拟体内使用。

Project Summary Over 700,000 Americans require cerebrospinal fluid (CSF) shunts to relieve excess cerebrospinal fluid pressure; however, >30% of these shunts fail within 2 years requiring multiple revision surgeries. Common causes of CSF shunt failure include aseptic clogging, infection and mechanical failure. Aseptic clogging is responsible for the majority of the failures, but is unaddressed in the marketplace. Passivation of silicone shunts against cell and tissue adhesion, as well as initial protein deposition and denaturation, is an attractive strategy to reduce the embolism and tissue ingrowth that underlies the frequency of revision surgery in hydrocephalus patients. This proposal examines a novel coating for the silicone shunts derived from ultralow attachment multiwell plates for organoids. We propose to develop a biocompatible surface-modification process for silicone implantables that, unlike other methods of silicone surface-modification, can bond permanently with silicone and resist hydrophobic recovery, a common occurrence whereby small silicone oligomers migrate through a coating to cover the surface again with silicone. In addition, the coating will resist >99% of cellular adhesion of CNS cells and tissues. To validate the technology and establish proof-of-principal, coated shunt tips will be evaluated for adhesion of microglia and astrocytes, brain tissue fragments, and choroid plexus tissue sheets in a hydrocephalus shunt catheter bioreactor system to mimic in vivo use.