title: Reduction of protein adsorption and macrophage and astrocyte adhesion on ventricular catheters by polyethylene glycol and N-acetyl-L-cysteine.
abstract: Cellular obstruction of poly(dimethyl)siloxane (PDMS) catheters is one of the most prevalent causes of shunt failure in the treatment of hydrocephalus. By modifying PDMS using short- and long-chain mono-functional polyethylene glycol (PEG604 and PEG5K, respectively) and N-acetyl-L-cysteine via adsorption and covalent binding (NAC and NAC/EDC/NHS, respectively), we increased surface wettability. We hypothesized that these surface modifications would inhibit protein adsorption and decrease host macrophage and astrocyte adhesion. Tested in a bioreactor set to mimic physiological flow, all modified surfaces significantly decreased albumin adsorption compared with PDMS (p < 0.05) except for PEG604-modified PDMS (p = 0.14). All four modification strategies significantly reduced (p < 0.01) fibronectin adsorption. PEG604, PEG5K, NAC, and NAC/EDC/NHS reduced the average level of macrophage adhesion by 53%, 63%, 40%, and 58% (p <.0.05 except when comparing PDMS with NAC) and astrocyte adhesion by 47%, 83%, 91%, and 72% (p < 0.05 except when comparing PDMS with PEG604), respectively. Combined with saline soak results which suggest that the surface wettability is stable over 30 days for each modification, our results are consistent with the hypothesis that these modifications decrease cell adhesion on catheters in vitro for the treatment of hydrocephalus.
authors.affiliation: Department of Neurosurgery, Division of Pediatric Neurosurgery, University of Utah, Salt Lake City, Utah 84132, USA. carolyn.harris@hsc.utah.edu
authors.forename: Carolyn A
authors.initials: CA
authors.lastname: Harris
authors.forename: James H
authors.initials: JH
authors.lastname: Resau
authors.forename: Eric A
authors.initials: EA
authors.lastname: Hudson
authors.forename: Richard A
authors.initials: RA
authors.lastname: West
authors.forename: Candice
authors.initials: C
authors.lastname: Moon
authors.forename: Andrew D
authors.initials: AD
authors.lastname: Black
authors.forename: James P
authors.initials: JP
authors.lastname: McAllister
mesh_terms: D000111:Acetylcysteine / Q000737:chemistry / Q000378:metabolism*; D000327:Adsorption; D000818:Animals; D001253:Astrocytes / Q000166:cytology*; D057785:Catheters; D002448:Cell Adhesion; D002460:Cell Line; D002478:Cells, Cultured; D020099:Coated Materials, Biocompatible / Q000737:chemistry / Q000378:metabolism*; D004129:Dimethylpolysiloxanes / Q000737:chemistry / Q000378:metabolism; D005353:Fibronectins / Q000378:metabolism; D008264:Macrophages / Q000166:cytology*; D051379:Mice; D011092:Polyethylene Glycols / Q000737:chemistry / Q000378:metabolism*; D011506:Proteins / Q000378:metabolism*; D051381:Rats; D012709:Serum Albumin / Q000378:metabolism; D017155:Wettability
chemical_list: D020099:Coated Materials, Biocompatible; D004129:Dimethylpolysiloxanes; D005353:Fibronectins; D011506:Proteins; D012709:Serum Albumin; D011092:Polyethylene Glycols; D000111:Acetylcysteine