Ultra-low attachment coatings to maintain CSF shunt patency

Project SummaryOver 700,000 Americans require cerebrospinal fluid (CSF) shunts to relieve excess cerebrospinal fluid pressure; however, andgt;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 andgt;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.Project Narrative More than 30% of implantable CSF shunts used to treat hydrocephalus fail within the first year. Shunt failure requires surgical reintervention which, if not performed in a timely manner can result in catastrophic consequences for patients, including brain damage or death. The primary unaddressed cause of shunt failure is clogging due to embolism and tissue ingrowth. This project will test a novel coating to reduce shunt failure by minimizing cell and tissue adhesion to the shunt material.