Making Silicone Rubber Highly Resistant to Bacterial Attachment Using Thiol-ene Grafting.

Biomedical devices are indispensable in modern medicine yet offer surfaces that promote bacterial attachment and biofilm formation, resulting in acute and chronic healthcare-associated infections. We have developed a simple method to graft acrylates to silicone rubber, polydimethylsiloxane (PDMS), a commonly used device material that is often colonized by bacteria. We demonstrate a novel method whereby nontoxic bacteria attachment-resistant polymers can be readily grafted from and grafted to the surface using thiol-ene chemistry, substantially reducing bacterial colonization. With use of this approach, bacterial biofilm coverage can be reduced by 99% compared with standard PDMS in an in vitro assay. This grafting approach offers significant advantages over commonly used physisorbed coatings, especially in areas of high shear or mechanical stress. Furthermore, the approach is versatile such that the grafted material properties can be tailored for the desired final application.

Amphiphilic block copolymers from a renewable ε-decalactone monomer: prediction and characterization of micellar core effects on drug encapsulation and release.

Here we describe a methoxy poly(ethyleneglycol)-b-poly(ε-decalactone) (mPEG-b-PεDL) copolymer and investigate the potential of the copolymer as a vehicle for solubilisation and sustained release of indomethacin (IND). The indomethacin loading and release from mPEG-b-PεDL micelles (amorphous cores) was compared against methoxy poly(ethyleneglycol)-b-poly(ε-caprolactone)(mPEG-b-PCL) micelles (semicrystalline cores). The drug-polymer compatibility was determined through a theoretical approach to predict drug incorporation into hydrated micelles. Polymer micelles were prepared by solvent evaporation and characterised for size, morphology, indomethacin loading and release. All the formulations generated spherical micelles but significantly larger mPEG-b-PεDL micelles were observed compared to mPEG-b-PCL micelles. A higher compatibility of the drug was predicted for PCL cores based on Flory-Huggins interaction parameters (χsp) using the Hansen solubility parameter (HSP) approach, but higher measured drug loadings were found in micelles with PεDL cores compared to PCL cores. This we attribute to the higher amorphous content in the PεDL-rich regions which generated higher micellar core volumes. Drug release studies showed that the semicrystalline PCL core was able to release IND over a longer period (80% drug release in 110 h) compared to PεDL core micelles (80% drug release in 72 h).

Bacteria-instructed synthesis of polymers for self-selective microbial binding and labelling.

The detection and inactivation of pathogenic strains of bacteria continues to be an important therapeutic goal. Hence, there is a need for materials that can bind selectively to specific microorganisms for diagnostic or anti-infective applications, but that can be formed from simple and inexpensive building blocks. Here, we exploit bacterial redox systems to induce a copper-mediated radical polymerization of synthetic monomers at cell surfaces, generating polymers in situ that bind strongly to the microorganisms that produced them. This 'bacteria-instructed synthesis' can be carried out with a variety of microbial strains, and we show that the polymers produced are self-selective binding agents for the 'instructing' cell types. We further expand on the bacterial redox chemistries to 'click' fluorescent reporters onto polymers directly at the surfaces of a range of clinical isolate strains, allowing rapid, facile and simultaneous binding and visualization of pathogens.