| Description |
Shunt catheter obstruction due to the foreign body host response is a serious problem in the treatment of hydrocephalus. Our goal was to reduce inflammatory cell adhesion on silicone catheters in an effort to limit shunt obstruction. We investigated chemical and mechanical cues that may influence macrophage and astrocyte adhesion, and using this knowledge, examined pertinent catheter modifications. A novel in vitro bioreactor, capable of measuring dependencies between macrophage and astrocyte adhesion, intracranial flow rate, pressure, pulsation frequency, and protein concentration, was developed and tested. Results demonstrated that a combination of chemical cues (particularly surface chemistry) and mechanical cues (particularly shear stress) influenced macrophage and astrocyte attachment to shunt catheters. The surface chemistry of the catheter was modified using long term coatings with anti-inflammatory capabilities including poly(ethylene) glycol and N-acetyl-L-cysteine, both of which significantly inhibited macrophage and astrocyte adhesion when tested in the bioreactor. Additionally, the shear stress through ventricular catheter drainage holes was manipulated by changing the diameter of these openings. Data generally suggested that macrophage and astrocyte adhesion decreases with increasing hole size. Two barriers were overcome in this research: (1) the development of an in vitro system capable of testing catheter constructs in a method superior to standard static in vitro culturing; (2) significant surface and architecture modifications that inhibit inflammatory cell adhesion which could be used in future studies to inhibit inflammatory-derived obstruction. Together, the implementation of this system and the modifications to current catheter design will help answer questions of how and why catheters fail. |
