Effects of surface wettability, flow, and protein concentration on macrophage and astrocyte adhesion in an in vitro model of central nervous system catheter obstruction

Abstract

While silicone devices have vastly improved an array of medical treatments, reactions at the tissue-substrate interface often impede their functionality. Insertion of a poly(dimethyl)siloxane (PDMS) catheter into the cerebral ventricles to drain excess cerebrospinal fluid (CSF) is the most common treatment of hydrocephalus, but shunting often fails because inflammatory tissue, choroid plexus cells, and debris grow into these central nervous system catheters and obstruct flow. We hypothesized that plasma oxidation of PDMS would inhibit macrophage and astrocyte adhesion under flow (0 to 0.3 mL/min) and protein (20.8 to 240 mg/dL) conditions similar to those observed in the physiological state. Oxidation (to increase wettability) had an inhibitory effect on macrophage cell binding (yielding a significant 88% change) that was generally more pronounced than the effect of flow (22% change) or protein concentration (3% change). In contrast, greater flow increased binding of astrocytes in most cases (yielding a significant 97% change); plasma oxidation (19% change), and protein concentration (60% change) had less pronounced effects. This study is the initial indicator that plasma oxidation of PDMS catheters may inhibit macrophage adhesion during CSF outflow but may not be as effective at inhibiting astrocyte binding.

Biocompatibility and inflammatory response in vitro and in vivo to gelatin-based biomaterials with tailorable elastic properties

“…This may be due to the rather low E-moduli of the materials (10e60 kPa), as earlier studies showed increasing macrophage attachment to materials with increasing Young's modulus, preferentially > 100 kPa [37]. Additionally, highly hydrophilic materials (like gelatin-based hydrogels) tend to show low macrophage adhesion [38]. In vivo, this might prevent their fusion to foreign body giant cells and thereby reduce the formation of fibrous scar tissue and the development of a chronic inflammation [39].…”

What We Should Know About the Cellular and Tissue Response Causing Catheter Obstruction in the Treatment of Hydrocephalus

“…Under static in vitro conditions, serum significantly influences macrophage 66 and neural-glial 67 adhesion, while a similar but nonsignificant trend was also found in fluidic in vitro cultures using macrophages and astrocytes. 68 These data are supported by a recent study that suggested that 23% of obstructed or infected shunts were from patients with protein concentration greater than 1.0 g/L. 69 The number of reactive astrocytes around other CNS implants appears to be proportionate to BBB dysfunction (and perhaps, then, an increased protein concentration).…”

“…117 Recent evidence suggests that astrocytes respond more to changes in flow than to surface chemistry, whereas the opposite is true for macrophages, implying that the effects of surface modifications may be more apparent in the short term. 68 Alternatives to inorganic polymeric surface modifications that may improve effectiveness of surface modifications include (but are not limited to) the incorporation or release of pharmaceutical agents such as N-acetyl-L-cysteine onto the surface of silicone to actively target specific surface interactions 113,114 ; bioactive agents such as antibodies that retard cytokine diffusion and reduce acute inflammation 118 ; natural polysaccharides such as heparin (which particularly showed poor outcome in vitro under static conditions, but improved under flow conditions 105,106 ); surfaces that mimic properties of native extracellular matrix or endothelial cell layers 119 ; inoculation with a clot-reducing, defibrinogenic agent, an anticoagulant, and a platelet inhibitor 120 ; and catheters constructed of living cells. 121 The living-cell approach, while initially unsuccessful, represents an extremely progressive and thought-provoking concept of reducing undesirable interactions between host cells/tissues and shunt catheters by seeding cells and their matrices onto biodegradable polymers and allowing the cells to act as the shunt system.…”

“…85,87,88 Modifying the degree of wetting (hydrophobicity/hydrophilicity) is an extremely useful parameter in guiding the biological interaction 89 (in addition to modification of surface charge and roughness 45,[90][91][92][93][94] ), but the influence of wettability is dictated by environmental conditions. 68,88,95 Under intracranial CSF flow rates, hydrophobic materials elicit more cell adhesion than hydrophilic surfaces, but this relationship depends on the surface coating and cell type. 68 One of the first modifications to silicone catheters was in 1991, when researchers in a small clinical trial used a ventriculosubdural shunt system made entirely of poly-2-hydroxyethyl methacrylate (pHEMA), a hydrophilic polymer that often has a gel-like consistency in water.…”

“…68,88,95 Under intracranial CSF flow rates, hydrophobic materials elicit more cell adhesion than hydrophilic surfaces, but this relationship depends on the surface coating and cell type. 68 One of the first modifications to silicone catheters was in 1991, when researchers in a small clinical trial used a ventriculosubdural shunt system made entirely of poly-2-hydroxyethyl methacrylate (pHEMA), a hydrophilic polymer that often has a gel-like consistency in water. 96 This study focused on the revival of the abandoned ventriculosubdural shunt approach, and the use of pHEMA was only briefly discussed.…”