Antimicrobial Peptide-Conjugated Hierarchical Antifouling Polymer Brushes for Functionalized Catheter Surfaces

Abstract

Catheter-related infection is a great challenge to modern medicine, which causes significant economic burden and increases patient morbidity. Hence, there is a great requirement for functionalized surfaces with inherently antibacterial properties and biocompatibility that prevent bacterial colonization and attachment of blood cells. Herein, we developed a strategy for constructing polymer brushes with hierarchical architecture on polyurethane (PU) via surface-initiated atom-transfer radical polymerization (SI-ATRP). Surface-functionalized PU (PU-DMH) was readily prepared, which comprised of poly­(3-[dimethyl-[2-(2-methylprop-2-enoyloxy)­ethyl]­azaniumyl]­propane-1-sulfonate) (PDMAPS) brushes as the lower layer and antimicrobial peptide-conjugated poly­(methacrylic acid) (PMAA) brushes as the upper layer. The PU-DMH surface showed excellent bactericidal property against both Gram-positive and Gram-negative bacteria and could prevent accumulation of bacterial debris on surfaces. Simultaneously, the PU-DMH samples possessed good hemocompatibility and low cytotoxicity. Furthermore, the integrated antifouling and bactericidal properties of PU-DMH under hydrodynamic conditions were confirmed by an in vitro circulating model. The functionalized surface possessed persistent antifouling and bactericidal performances both under static and hydrodynamic conditions. The microbiological and histological results of animal experiments also verified the in vivo anti-infection performance. The present work might find promising clinical applications for preventing catheter-related infection.

Theoretical and Experimental Optimization of the Graft Density of Functionalized Anti-Biofouling Surfaces by Cationic Brushes

“…The adsorbed proteins were separated by 20 min ultrasonication in the SDS solution. The adsorbed protein content was determined by the BCA protein quantification kit, using a standard protein solution as the calibration standard [ 39 , 40 ].…”

“…The PU samples, equilibrated with PBS overnight, were placed in a 24-well plate and incubated at 37 °C for 24 h, after which the samples were washed with PBS to remove non-adherent bacteria, fixed with a 2.5 wt% glutaraldehyde aqueous solution, and stored at 4 °C for 4 h. The resulting samples were soaked in several ethanol/distilled water solutions (1:1, 3:2, 7:3, 4:1, and 5:0 (by volume) in sequence, 15 min for each solution) for dehydration. The resulting samples were freeze-dried, sprayed with gold, and analyzed for adhered bacteria using a JSM-5610LV scanning electron microscope (SEM) by JEOL (Tokyo, Japan) [ 26 , 40 ].…”

Minimising Blood Stream Infection: Developing New Materials for Intravascular Catheters

“…Putting the issue of dwell time aside, the release of antibiotic moieties (i.e., rifampicin) have a long history but the increasing threat of bacterial resistance has driven considerable effort to examine alternative antimicrobial agents. Various antimicrobial peptides [100,108,[113][114][115], guanidine derivatives (i.e., poly hexamethyl biguanide, polyarginines) [103,104], quaternary ammonium compounds [96,98], nitric oxide precursors [105,106,116,117], silver [118][119][120] and a host of other small molecules/metal ions or nanoparticles [107,110,118,[121][122][123][124] with possible biocidal activity have all been investigated as potential modifiers for use in catheters and, while these invariably impact bacterial colonisation, they have yet to make the leap to commercial exploitation and/or substantive clinical trials.…”

“…Contact killing of bacteria, in contrast to passive elution, relies on the immobilisation of the antimicrobial at the catheter surface and, as such, sets out to present a lethal barrier to the microbes attempting to colonise the catheter surfaces [96,98,100,104,114,115,119,125,126]. Grafting through plasma processes, polymerisation of a biocide functionalised monomer, covalent linkage (i.e., click chemistry) onto side chains or the deposition of insoluble layers are common techniques through which the catheter interface can be functionalised.…”

“…Prevention of fouling has been the second main route through which to avoid biofilm formation and minimise the risk of both CRBSI [97,99,114,127] and catheter related thrombotic complications [128][129][130][131]. The latter can be categorised into four types: mural thrombosis, ball-valve-thrombosis, intraluminal thrombotic occlusion and, the most common cause, pericatheter sheath [128][129][130][131].…”