Application of Targeted Molecular and Material Property Optimization to Bacterial Attachment-Resistant (Meth)acrylate Polymers

Abstract

Developing medical devices that resist bacterial attachment and subsequent biofilm formation is highly desirable. In this paper, we report the optimization of the molecular structure and thus material properties of a range of (meth)acrylate copolymers which contain monomers reported to deliver bacterial resistance to surfaces. This optimization allows such monomers to be employed within novel coatings to reduce bacterial attachment to silicone urinary catheters. We show that the flexibility of copolymers can be tuned to match that of the silicone catheter substrate, by copolymerizing these polymers with a lower Tg monomer such that it passes the flexing fatigue tests as coatings upon catheters, that the homopolymers failed. Furthermore, the Tg values of the copolymers are shown to be readily estimated by the Fox equation. The bacterial resistance performance of these copolymers were typically found to be better than the neat silicone or a commercial silver containing hydrogel surface, when the monomer feed contained only 25 v% of the "hit" monomer. The method of initiation (either photo or thermal) was shown not to affect the bacterial resistance of the copolymers. Optimized synthesis conditions to ensure that the correct copolymer composition and to prevent the onset of gelation are detailed.

Real time monitoring of biofilm formation on coated medical devices for the reduction and interception of bacterial infections

“…57,58 The object labels/description of 'coated' represents samples that had been first silane primed and then polymer coated. The polymer was prepared using catalytic chain transfer radical polymerisation, 20 resulting in a polymer with a molecular weight of 1.8 × 10 4 g mol −1 and a polydispersity index of 1.6 (Table S1 †). The polymer was applied to the ETT and optical fibre by dip coating, producing coatings with mean thicknesses of 0.6 and 0.5 µm respectively, excluding the primer layer (measured by weighing samples of known dimensions pre-and post-coating, and measuring the density of the polymer, which was 1.6 g cm −3 ).…”

“…On coated systems, no wavelength shift was observed, indicating low biofilm formation, which is consistent with previous studies. 19,20 Some cells may have attached, but at a level below the refractive index limit of detection of the LPG sensor (estimated to be 0.001 refractive index units). [54][55][56] The detection of bacteria by the sensor was limited to the region of the evanescent field, [39][40][41][42] which, for the sensors used in this study, was greater than 0.5 µm from the cladding surface (see ESI, † 'LPG optical fibre sensor considerations').…”

“…18 Recently, we reported a new class of amphiphilic polymers resistant to biofilm formation that achieved two orders of magnitude reduction in bacterial numbers within a murine subcutaneous infection model. 19 A reduction in biofilm formation was demonstrated on these polymers for the bacterial species P. aeruginosa, Staphylococcus aureus and Escherichia coli in a urinary catheter context 19,20 which may be relevant for preventing infections on ETTs. This reduction in biofilm formation is attributed to the chemical structure of the pendant groups of the polymer.…”

Innovations in indwelling urethral catheterisation

“…Camstent Ltd. (Cambridge, UK) has manufactured a commercially available antifouling polymer‐coated silicone catheter, with demonstrated reduction in biofilm formation compared with standard uncoated catheters in a first‐in‐man pilot study . The novel antifouling polymer was identified by a high throughput microarray method, which tested attachment of bacterial species to hundreds of different polymers . Coating silicone with the novel polymer achieved a 30‐fold reduction in surface area colonised with bacteria in vitro .…”

“…The novel antifouling polymer was identified by a high throughput microarray method, which tested attachment of bacterial species to hundreds of different polymers . Coating silicone with the novel polymer achieved a 30‐fold reduction in surface area colonised with bacteria in vitro . Surface topographical approaches can also reduce biofilm formation.…”