Tackling catheter-associated urinary tract infections with next-generation antimicrobial technologies.

Urinary catheters and other medical devices associated with the urinary tract such as stents are major contributors to nosocomial urinary tract infections (UTIs) as they provide an access path for pathogens to enter the bladder. Considering that catheter-associated urinary tract infections (CAUTIs) account for approximately 75% of UTIs and that UTIs represent the most common type of healthcare-associated infections, novel anti-infective device technologies are urgently required. The rapid rise of antimicrobial resistance in the context of CAUTIs further highlights the importance of such preventative strategies. In this review, the risk factors for pathogen colonization in the urinary tract are dissected, taking into account the nature and mechanistics of this unique environment. Moreover, the most promising next-generation preventative strategies are critically assessed, focusing in particular on anti-infective surface coatings. Finally, emerging approaches in this field and their likely clinical impact are examined.

Engineering the Biointerface of Electrospun 3D Scaffolds with Functionalized Polymer Brushes for Enhanced Cell Binding.

Electrospun ultrafine fibers prepared using a blend of poly(lactide- co-glycolide) (PLGA) and bromine terminated poly(l-lactide) (PLA-Br), were surface modified using surface-initiated (SI) Cu(0) mediated polymerization. Copolymers based on N-acryloxysuccinimide (NAS) and a low fouling monomer (either N, N-dimethylacrylamide (DMA), N-(2-hydroxypropyl)acrylamide (HPA), or N-acryloylmorpholine (NAM)) were grafted from the fiber surface to impart surface functionality and to reduce nonspecific protein adsorption. Inclusion of the functional NAS monomer facilitated the conjugation of a nonbioactive cyclic RAD peptide and a bioactive cyclic RGD peptide, the latter expected to facilitate cell adhesion through its affinity for the αvß3 integrin receptor. A detailed analysis of the surface of the electrospun fiber scaffolds in nongrafted form compared to the surface functionalized state is presented. Characteristic amino acid peaks are observed for both conjugated RGD and RAD peptides. Cell culture experiments confirmed cell specific attachment mediated through the presence of the bioactive RGD peptide mainly at high surface density.

Optimisation of grafting of low fouling polymers from three-dimensional scaffolds via surface-initiated Cu(0) mediated polymerisation.

Electrospun fibres represent a realistic implantable scaffold containing most of the structural three-dimensional (3D) characteristics of the extracellular matrix. However, as a result of their often synthetic nature, surface energy and chemistry, these scaffolds may adsorb a layer of non-specific proteins which can evoke a foreign body response. The precise surface modification of the scaffolds is challenging due to the complex geometrical and structural organization of the fibre meshes, that may limit the efficacy and completeness of approaches used. One flexible strategy that has gained attention is the use of reversible deactivation radical polymerisation (RDRP) techniques, which allow the creation of polymer brushes with controlled molecular weight, whilst retaining fibre morphology. In this study, protein adsorption was reduced with grafting of poly(N,N-dimethylacrylamide) (PDMA), poly(N-(2-hydroxypropyl)acrylamide) (PHPA) and poly(N-acryloylmorpholine) (PNAM) via surface-initiated (SI)-Cu(0) mediated radical polymerisation, from the surface of electrospun fibres prepared using a blend of bromine terminated poly(l-lactide) (PLA-Br) and poly(d,l-lactide-co-glycolide) (PLGA). Optimisation of the levels of Cu(i)Br, Me6TREN and the presence and concentration of a sacrificial initiator facilitated the grafting of well-controlled polymers brushes in less than one hour. Surface characterisation of the grafted scaffolds using X-ray photoelectron spectroscopy (XPS) and time of flight secondary ion mass spectroscopy (ToF-SIMS), and direct analysis of the molecular weight and polydispersity of polymer formed in solution during the reaction as well as the grafted polymer layer confirmed successful, controlled modification. Finally, protein adsorption experiments demonstrated the low adsorption properties of all polymer coatings with PDMA showing superior performance.

Surface modification of electrospun fibres for biomedical applications: A focus on radical polymerization methods.

The development of electrospun ultrafine fibres from biodegradable and biocompatible polymers has created exciting opportunities for biomedical applications. Fibre meshes with high surface area, suitable porosity and stiffness have been produced. Despite desirable structural and topographical properties, for most synthetic and some naturally occurring materials, the nature of the fibre surface chemistry has inhibited development. Hydrophobicity, undesirable non-specific protein adsorption and bacterial attachment and growth, coupled with a lack of surface functionality in many cases and an incomplete understanding of the myriad of interactions between cells and extracellular matrix (ECM) proteins have impeded the application of these systems. Chemical and physical treatments have been applied in order to modify or control the surface properties of electrospun fibres, with some success. Chemical modification using controlled radical polymerization, referred to here as reversible-deactivation radical polymerization (RDRP), has successfully introduced advanced surface functionality in some fibre systems. Atom transfer radical polymerization (ATRP) and reversible addition fragmentation chain transfer (RAFT) are the most widely investigated techniques. This review analyses the practical applications of electrospinning for the fabrication of high quality ultrafine fibres and evaluates the techniques available for the surface modification of electrospun ultrafine fibres and includes a detailed focus on RDRP approaches.