title: A strategy to passively reduce neuroinflammation surrounding devices implanted chronically in brain tissue by manipulating device surface permeability.
abstract: Available evidence indicates that pro-inflammatory cytokines produced by immune cells are likely responsible for the negative sequela associated with the foreign body response (FBR) to chronic indwelling implants in brain tissue. In this study a computational modeling approach was used to design a diffusion sink placed at the device surface that would retain pro-inflammatory cytokines for sufficient time to passively antagonize their impact on the FBR. Using quantitative immunohistochemistry, we examined the FBR to such engineered devices after a 16-week implantation period in the cortex of adult male Sprague-Dawley rats. Our results indicate that thick permeable surface coatings, which served as diffusion sinks, significantly reduced the FBR compared to implants either with no coating or with a thinner coating. The results suggest that increasing surface permeability of solid implanted devices to create a diffusion sink can be used to reduce the FBR and improve biocompatibility of chronic indwelling devices in brain tissue.
authors.affiliation: Department of Bioengineering, University of Utah, James LeVoy Sorenson Molecular Biotechnology Building (SMBB), 36 S. Wasatch Drive, Rm. 3100, Salt Lake City, UT 84117, USA.
authors.forename: John L
authors.initials: JL
authors.lastname: Skousen
authors.affiliation: Department of Bioengineering, University of Utah, James LeVoy Sorenson Molecular Biotechnology Building (SMBB), 36 S. Wasatch Drive, Rm. 3100, Salt Lake City, UT 84117, USA.
authors.forename: Michael J
authors.initials: MJ
authors.lastname: Bridge
authors.affiliation: Department of Bioengineering, University of Utah, James LeVoy Sorenson Molecular Biotechnology Building (SMBB), 36 S. Wasatch Drive, Rm. 3100, Salt Lake City, UT 84117, USA. Electronic address: Patrick.Tresco@utah.edu.
authors.forename: Patrick A
authors.initials: PA
authors.lastname: Tresco
mesh_terms: D000818:Animals; D001921:Brain / Q000276:immunology*; D016207:Cytokines / Q000276:immunology; D020342:Finite Element Analysis; D005549:Foreign-Body Reaction / Q000209:etiology* / Q000276:immunology / Q000517:prevention & control*; D008297:Male; D010539:Permeability; D019736:Prostheses and Implants / Q000009:adverse effects*; D017207:Rats, Sprague-Dawley
chemical_list: D016207:Cytokines
keywords: Cytokine; Electrode; Finite element analysis; Foreign body response; Inflammation; Macrophage