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Following adverse clinical events involving seven patients undergoing renal dialysis using 12-year-old cellulose acetate hemodialyzers, this in vitro study was proposed in an effort to characterize the inflammatory response to the constituent cellulose acetate (CA) fiber materials. Chemiluminescence (CL) and apoptosis assays were used to determine whether human neutrophils were activated by CA fiber materials and/or are sensitive to degradation/alteration of these fibers over time. Furthermore, the study examined in vitro assays with human neutrophils using a CA film, the solvents used in the film preparation and CA resin. The film could be cut to identical sized pieces in an effort to compare hemodialysis material effects in standardized amounts. For the CL assays, 60-min exposure was followed by secondary stimulation with n-formyl-met-leu-phe (fMLP) or phorbol-12-myristate-13-acetate (PMA). Short-term exposure (60-min postintroduction to CA materials) increased the inflammatory response as measured by the respiratory burst of neutrophils (p < or =.05), with CA fiber exposure significantly compared with cells alone. There was a trend toward an increased response with exposure to older fibers with secondary PMA stimulation. Apoptosis was increased 12% with exposure to the more aged fibers versus 2% with the new fibers. The fiber storage component, glycerol, significantly inhibited the oxidative response (p < or =.001; > or =80% suppression with concentrations of 5-20%). The solvents used in film preparation, N,N-dimethylacetamide and tetrahydrofuran, produced greater than a 70% and 60% suppression, respectively, of CL activity for all concentrations > or =1%. More work is needed to determine the specific nature of the interaction of inflammatory cells with CA materials, but early evidence suggests that neutrophils are activated by CA and display an altered response to more aged fibers., (Copyright 2001 John Wiley & Sons, Inc. J Biomed Mater Res 55: 257-265, 2001)

Cells are sensitive to topological, chemical, and electrical properties of substrates on which they are grown. However, most studies of cell-surface interactions have neglected electrical effects or confounded them with other substrate properties. The use of nanofabrication technology has made it possible to fabricate optically transparent surfaces with controlled chemistry and topology, and with active, controllable surface charge density in domains as small as 1-4 microns. Human monocytes incubated on polystyrene with 3.3 microns-wide strip domains, alternately charged so as to maintain overall charge neutrality, show significant charge density and time-dependent increases (greater than twofold) in cell area and cell perimeter after challenge with a phagocytic trigger (human IgG opsonized zymosan particles). Additional utlrastructural studies on silicon dioxide substrates show charge-density-dependent qualitative morphological differences. These studies clearly demonstrate that human monocytes respond in vitro to local surface-charge heterogeneity in the absence of substrate topology and compositional variation.

Developers of biosensors as medical devices are using emerging technologies that incorporate chemical assays with fiber optics and semiconductors. These biosensors will eventually become indwelling catheters for monitoring blood analyte concentrations as well as functioning as controlled feedback elements for artificial organs. Materials used in these devices are subject to problems of manufacture and reliability as well as those induced by the human body's response to these "foreign agents." The Division of Mechanics and Materials Science in the Center for Devices and Radiological Health at the Food and Drug Administration has initiated a program to investigate factors that effect sensitivity, selectivity and reliability of sensors used in biological applications. Our group's principle focus is on sensors of chemical processes. This article is an outgrowth of our research efforts and is a review of some of the technologies that are currently available or becoming available for these applications. The goal of our research is to identify factors that will have an impact on the reliability of long-term implanted medical devices with particular attention to sensors used in feedback-controlled therapeutic systems.