Direct introduction of phosphonate by the surface modification of polymers enhances biocompatibility Cleo Choong b,1 , Jon-Paul Griffiths a , Mark G. Moloney a, * , James Triffitt b , Diane Swallow a a Department of Chemistry, Chemical Research Laboratory, University of Oxford, Mansfield Rd., Oxford OX1 3TA, UK b Institute of Musculoskeletal Sciences, Botnar Research Centre, Nuffield Orthopaedic Centre, University of Oxford, Headington, Oxford OX3 7LD, UK article info Article history: Received 22 February 2008 Received in revised form 28 October 2008 Accepted 2 November 2008 Available online 14 November 2008 Keywords: Surface Modification Biocompatibility abstract A novel chemical method for the modification of polystyrene and nylon polymers by the reaction of diaryl carbenes permits the direct and efficient introduction of phosphonate residues upon the polymer surface. The method is simple to execute, involving solution coating to adsorb the reactive coating agent, followed by drying and thermolysis at temperatures not greater than 150 °C. This material can be further modified to the calcium phosphonate derivative, by treatment with aqueous calcium hydroxide. The modified polymers show enhanced biocompatibility of the modified polymer, as evidenced by the improved growth of MG63 human osteosarcoma cell line on the surface. This method is of significance since it offers a simple chemical protocol for the tailoring of the surface properties of materials, it avoids the need to construct ab initio new polymers for a given application, it provides an alternative to existing surface modification protocols, and it extends the range of polymers suitable as biocompatible materials . Ó 2008 Elsevier Ltd. All rights reserved. 1. Introduction Surgically implanted materials, derived from polymers, ceram- ics or metals, are neither fully inert under physiological conditions nor become fully integrated with surrounding tissue. Upon implan- tation, all evoke an immune response from the host, and the nature and extent of this response appears to depend on the mechanical properties, surface and bulk chemistry, surface topography and porosity, and rate and nature of decomposition of the implant [1]. A fully biocompatible biomaterial should elicit a minimal inflam- matory response, together with the desired specific tissue response. However, polymers, used as scaffolds in bioengineering applica- tions, rarely exhibit all of the properties required in this role; [2] for example, their structural properties may be compromised by poor biocompatibility or biodegradability. There has therefore been intense activity to develop novel biocompatible materials suitable for use in tissue culture and medical implant applications [3]. One approach in this endeavour is to modify the surface of com- monly used and readily available materials to improve their bio- compatibility, but without changing the desired bulk (for example, flexibility or mechanical) properties [4,5] and the possi- bility of the control of cell adhesion by modification of surface topography has been demonstrated [6–9]. Attempts to control sur- face properties by modification of the surfaces of bulk materials have been made [4,5] and a recent study has shown that functional surfaces carrying amino groups exhibit a five-fold enhancement of cell adhesion over the unmodified surfaces, and that carboxylic acid and hydrocarbon functions decrease adhesion by 2–5 times [10]. Significantly, the amino modified surface also exhibited im- proved adhesion over immobilised RGD tri-peptides [11]. The importance of calcium phosphate as a binding agent for cancer cells to surfaces was recognized long ago [12] and since then the incorporation of phosphate residues onto the surface of polymers to induce biomineralisation and cell adhesion has been of interest. This concept has met with mixed success, [13] although high levels of cell proliferation and adhesion is achievable by grafting a poly- vinyl phosphonate layer onto the surface of a silicon wafer [14]. In this work, between 10 and 15-fold enhancements were possible depending on the phosphonate content of the grafted layer. The enhancement of biocompatibility by the introduction of hydroxy- apatite onto a surface is a common strategy [13,15–21] especially for bone cell growth, [22] and we have shown that apatite-modi- fied caprolactone is accessible for medical applications [23–28]. Recently, it has been shown that chemical modification of polyure- thanes to introduce zirconia improves biocompatibility of fibro- blast cells, [29] and that the polyurethane–hyaluronic acid copolymers improve haemocompatibility [30]. Significant progress in the development of novel approaches to surface modification has been made, and a review of the attach- ment of bioactive compounds to a wide variety of putative bioma- terials has appeared [31]. Thus, chemical vapour deposition, [32] beam irradiation, [33] corona discharge, [34] surface patterning, 1381-5148/$ - see front matter Ó 2008 Elsevier Ltd. All rights reserved. doi:10.1016/j.reactfunctpolym.2008.11.003 * Corresponding author. Tel.: +44 186 527 5656. E-mail address: mark.moloney@chem.ox.ac.uk (M.G. Moloney). 1 Current Address: Institute of Bioengineering and Nanotechnology, 31 Biopolis Way, The Nanos #08-01, Singapore 138669, Singapore. Reactive & Functional Polymers 69 (2009) 77–85 Contents lists available at ScienceDirect Reactive & Functional Polymers journal homepage: www.elsevier.com/locate/react