Crosslinkable coatings from phosphorylcholine-based polymers
Introduction
We have previously described a family of proprietary polymers based on the combination of 2-methacryloyloxyethyl phosphorylcholine (MPC) with other methacrylate-type comonomers, in particular lauryl methacrylate (LMA) [1], [2]. It has been demonstrated that these materials impart enhanced biocompatibility and moreover, haemocompatibility, upon the surfaces onto which they are coated [3], [4], [5]. Phosphorylcholine (PC) is a zwitterionic head group that is present in high concentration in the outer leaflet of the lipid bilayer of red blood cell membranes, in the form of the phospholipid, phosphatidylcholine. It is generally accepted that the non-thrombogenic nature of the PC group is due to the fact that it is able to resist the adsorption of proteins, a process vital to thrombus formation [6]. A number of mechanisms have been proposed in the literature, including structured water layers [7] or phospholipid adsorption [5], [8] amongst others, that attempt to account for this phenomenon. Whatever be the mode of action, these PC-based materials are demonstrating significant clinical benefits within the medical device arena [9], [10], [11], [12], [13].
With the basis of a non-thrombogenic material now defined, the challenge is to further modify the polymer architecture to bring about more specific properties relevant to a wider range of applications. We have coated these polymers onto a variety of medical devices used in blood-contacting applications in order to reduce the extent of thrombosis. It was recognised that a crosslinkable coating would offer additional advantages over the existing systems in terms of stability of the film and the possibility of anchoring the polymer to the substrate. This would be particularly useful in applications where there was a potential for the coating to become denuded by physical handling of the device, or indeed where a change in the shape or dimension of the device might ensue.
This paper describes the development of a polymer system that can be cross-linked by a thermal curing process after coating onto the substrate. The crosslinking agent used was 3-(trimethoxysilyl)propyl methacrylate, as it is well documented in the literature [14], [15], [16], [17], [18], it is commercially available and is likely to have similar reactivity to the other methacrylate monomers in the system. The amount of crosslinking agent was balanced in order to produce an element of elasticity and significant improvement in the physical characteristics of the coating, whilst preventing embrittlement. Some studies on the physical and biological characteristics of the coating are presented.
Section snippets
Materials
2-Methacryoyloxyethylphosphorylcholine (MPC) was prepared according to the method previously described by us [1], [2]. This material is a white amorphous hygroscopic solid which must be handled with care to avoid excess hydration. , and NMR, FT-IR and elemental analysis confirm excellent product purity. All monomers other than MPC were obtained from the Aldrich Chemical Co. and used without further purification. These included lauryl methacrylate (LMA), 2-hydroxypropyl methacrylate
Membrane properties
Membrane formulations were based upon well-characterised MPC : LMA2 copolymer (or MPC33LMA67 for better comparison with the crosslinkable polymers) [1], [2], [3], with inclusion of between 1 and 10 mol% TSMA for crosslinking capability. At TSMA contents <5%, the membranes did not form properly or were `tacky’ and difficult to remove from the mould. For those in which TSMA was >5%, membrane formation was still inconsistent and any materials that were isolated were found to be very brittle. This is
Conclusions
Using polymer membranes as model systems, we have designed, synthesised and characterised a series of copolymers, largely based on MPC and LMA, that have post-crosslinkable capabilities. Further study of the physical properties of coatings of these materials have been performed using AFM and nanoindentation. The polymer described by the molar reaction feed ratios MPC23LMA47HPMA25TSMA5 has been shown to be ideal [27]. Glass and stainless-steel substrates have been dip-coated from ethanolic
Acknowledgements
The authors would like to thank Mr Lee Rowan and Mr Chris Allan for their contributions towards this work. Thanks also to Mr Neil Martin for providing assistance with NMR analysis and Mr Ray Burr for co-ordinating the nanoindentation studies.
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