Inert Coating for Cerebral Shunts to Eliminate Clogging

PROJECT SUMMARY ABSTRACTHydrocephalus patients suffer from long term deficits in both neurologic function and overall quality of lifeCurrent treatments in the fieldmost of which involve diversion of cerebrospinal fluidCSFwith shuntsrecurrently failDespite our efforts foryearsshunts still have the highest failure rate of any neurological deviceof all shunts fail after ten yearsThis failure rate is the dominant contributor to the $billion peryear cost that hydrocephalus incurs on our health care systemShunts fail after becoming obstructed with attaching gliacreating a substrate for more glia or other cells and tissuese gchoroid plexusto secondarily bind and block the flow of CSF through the shuntSince glial attachment is a primary mechanism for shunt failurewe need to prevent it by inhibiting surface interactions with proteinsastrocytesand microgliaTethered liquid perfluorocarbonTLPcoatings stably adheres a thininert liquid perfluorocarbon layer that prevents protein and cell attachment and subsequent activationPreviously developed solid surface coatingseven solid perfluorocarbon coatingsallow for some level of surface attachment and activationwhich eventually leads to recruitment of thrombotic proteins and inflammatory cellsThe omniphobic liquid surface repels hydrophilic and hydrophobic proteinspreventing recruitment and downstream cascades from initiating on the surface and leading to cloggingBased on our preliminary data which shows stabilitylow neurotoxicitydecreased protein adsorptioncell attachmentblood poolingand tissue responsethis is a top candidate to reduce shunt failure rateIn our first approachwe refine our coating technology to develop a durable and uniform coatingWe measure initial surface characteristicstest durability under high flow rates and following purposeful scratching and bendingand assess the impact any free floating TLP coating may have on shunt functionalityOur second aim begins to biologically analyze these relationships in aD culture systemdesigned and validated specifically to incorporate the shunt environmentBy using quantitative immunofluorescence to identify attachmentactivationmigrationproliferationand binding strengthwe will begin to understand the mechanisms of obstruction with and without the TLP coatingIn this waywe can use these data to make specific hypotheses driven design changesFinallyin our third approachwe will test toxicity in the brain and systemically by inserting TLP coated shunts into the rodent brainThis Phase I project sets FreeFlow apart from others with its novel TLP coating that will reduce shunt failureThis project will set the stage for Phase II pre clinical trials PROJECT NARRATIVEHydrocephalus patients have a severely diminished quality of life and suffer from longterm neurologic deficits because of the inevitable failure of shunts used to treatIn this projectour team of engineersneurosurgeonschemistsand biological experts will develop a stable and uniform coating that reduces glial cell attachment in a clinically significant waywhile also identifying how it works in order to maximize impactBy studying efficacy and mechanism of action in aD cell culture modeland safety in an in vivo modelwe embrace a multidisciplinary approach that will provide a better understanding and a newmodified shuntthat can be tested in pre clinical trials