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.