A sol-gel route to zinc and titanium-modified electrospun polyurethane as an alternative material for hydrocephalus shunt catheters

Introduction: Hydrocephalus is a clinical condition arising from the accumulation of cerebrospinal fluid within the ventricles of the brain. The main treatment for this condition involves the insertion of a shunt catheter to bypass the blockage and allow the CSF to drain from the ventricles, thus alleviating the build-up of intracranial pressure that would otherwise prove fatal. Such catheters, which are commonly made from medical grade silicone, are subject to high incidence of mechanical failure, infection and blockage owing to cerebral tissue infiltration and bacterial colonisation [1]. Increasing the degree of hydrophilicity of the catheter has been reported as an effective way to decrease cell adhesion and at the same time increase resistance to bacterial colonisation. Here, medical grade polyurethane was modified with the addition of inorganic modifiers (titanium and zinc) via a sol-gel process. Experimental methods: Electrospun medical grade polyurethane (Z6A1 b9 ‘A’ series thermoplastic poly-ether urethanes, Biomer Technology Ltd., Runcorn, UK) was modified either with zinc or titanium via a sol-gel process during the electrospinning process itself. Analysis of fibre diameter was conducted via scanning electron microscopy, while cell viability and apoptosis were quantified with a colorimetric assay (alamarBlue®, ABDserotec, Kidlington, UK) and cell apoptosis assay (Cell-APOPercentageTM, Biocolor Ltd., UK), respectively. Bacteria colony forming units were determined by a serial dilution method on agar plates. Image: Results and discussions: The sol-gel process has a direct impact on the diameter size and distribution of the fibres, with modified materials exhibiting a narrower diameter distribution as compared to unmodified electrospun polyurethane (Fig. 1). Upon exposure to human immortalised astrocyte cultures, modified electrospun materials exhibit a significantly lower viability than the positive control (Fig. 2A), and a higher apoptotic rate than the negative control (PDMS; Fig. 2B). Preliminary results suggest that cell adhesion is relatively large on more adhesive electrospun materials, while at the same time being lower for materials with smaller fibre diameters. Results from bacterial colonisation studies show that nanostructured surfaces are effective in controlling and reducing Staphylococcus aureus colonisation (1 Log10 unit reduction), as compared to the standard silicone (Fig. 3). Conclusions: Successful modification of polyurethane with zinc and titanium was achieved. Human astroglioma cell cultured for 9 days on modified electrospun materials exhibited lower viability and higher apoptosis rates. Incubation with Staph. aureus cultures showed a 1 Log unit reduction in colony forming units on the modified electrospun surfaces compared to PDMS control surfaces. The results from this preliminary in-vitro investigation are promising and support further research to explore the potential of such materials for this application. References/Acknowledgements: References 1. Harris, C. A., et al. (2011). Effects of surface wettability, flow, and protein concentration on macrophage and astrocyte adhesion in an in vitro model of central nervous system catheter obstruction. Journal of Biomedical Materials Research Part A, 97A(4), 433–440. Disclosure of Interest: D. Erbogasto Conflict with: The authors wish to acknowledge the support of the UK Engineering & Physical Sciences Research Council (EPSRC) Doctoral Training Centre in Medical Devices, University of Strathclyde (EPSRC Grant Ref. EP/F50036X/1) for the studentships awarded to DE., Conflict with: The polyurethanes used in this study were made available under the terms of a Materials Transfer Agreement with Biomer Technology Ltd., a UK-based manufacturer of high-performance polymers and products for the healthcare market., R. A. Black Conflict with: UK Engineering & Physical Sciences Research Council (EPSRC) Doctoral Training Centre in Medical Devices, University of Strathclyde (EPSRC Grant Ref. EP/F50036X/1), Conflict with: The polyurethanes used in this study were made available under the terms of a Materials Transfer Agreement with Biomer Technology Ltd., a UK-based manufacturer of high- performance polymers and products for the healthcare market.