Biomaterials
Development of Anti-Occlusion Ventricular Catheters for Treatment of Hydrocephalus
Haritosh Patel
Ph.D. Student
Harvard University, United States
Yu Xuan Huang
Undergraduate Student
University of Toronto
MARKHAM, Ontario, Canada
Duygu Dengiz
Ph.D. Student
Inorganic Functional Materials, Faculty of Engineering, Kiel University, Kiel, Germany, United States
Ida Pavlichenko
Postdoctoral Fellow
Harvard University, United States
Isil Winkler
Doctoral Researcher
Schleswig-Holstein University, United States
Luise Schlotterose
Doctoral Researcher
Kiel University, United States
Jack Alvarenga
Research Scientist
Harvard John A. Paulson School of Engineering and Applied Sciences, Harvard University; Boston, MA, 02134, USA, United States
James Weaver
Senior Scientist
Harvard University, United States
Kirsten Hattermann
Professor
Kiel University, United States
Olav Jansen
Professor
Kiel University, United States
Eckhard Quandt
Professor
Kiel University, United States
Joanna Aizenberg
Professor
Harvard John A. Paulson School of Engineering and Applied Sciences, Harvard University; Boston, MA, 02134, USA, United States
Dawn Ann Bordenave, Post-Bachelor (she/her/hers)
Research Intern
Harvard University
Boston, Massachusetts, United States
Hydrocephalus is an abnormal buildup of cerebrospinal fluid (CSF) in the ventricles deep within the brain (Fig 1a). The current treatment option for hydrocephalus are ventricular-peritoneal catheters which divert excess fluid away from the brain space reducing the overall pressure buildup. Despite development of various designs, ventricular catheters have consistently had complications with infection and obstruction. A 5-15% infection rate is reported largely due to the catheter's material failing to reduce bacterial colonization and cell adhesion. In addition, obstruction which is caused in nearly 50% of patients by choroid plexus, astrocytes, and microglial cells that adhere to the inlet holes prevents further drainage and function of the device. We want to design a new ventricular catheter that reduces both the rate of the infection and obstruction to minimize catheter related complications. Our approach to solving this problem is to synergistically improve material to prevent bioadhesion and secondly improve geometric design for flow.
A bioadhesive assay of Staphylococcus epidermidis (ATCC 12228) was performed on standard of care ventricular catheter pieces and silicone oil (350 cP) infused Sylgard 184 polydimethylsiloxane (PDMS).
For this study, the optical density at 600 nm (OD600) was used to track the growth of the bacteria in tryptic soy broth (TSB) medium. . Each sample was incubated with 106 CFU/mL of S. epidermidis at 23°C (15 rpm shaking). All samples were triple rinsed with phosphate buffer saline (PBS) to remove any loosely adhered or settled bacteria, followed by a crystal violet staining protocol. The OD570 reading of stained samples were measured by plate reader spectrophotometer.
Additionally, a dynamic flow experiment was conducted in which catheters were placed in a broth containing 105 CFU/mL of S. epidermidis and drained in an open loop for 1 hour. After, the catheters were rinsed with PBS, CV stained, and photographed.
Secondly, a flow analysis study was performed on standard of care ventricular catheters via FEM simulations. In this study, a 2D-box computational fluid dynamics (CFD) simulation was performed using COMSOL which tracked the relative flow through various inlet holes. The flow pattern was confirmed using an India Ink experiment. The India Ink experiment tracked flow using a low-diffusive dye in deionized water.Furthermore, we developed a more anatomical accurate ventricular model for hydrocephalus simulations. Herein, we added a particle tracking module and CFD module to accurately analyze flow and biomatter transport.