Validating a Predictive Structure–Property Relationship by Discovery of Novel Polymers which Reduce Bacterial Biofilm Formation

Abstract

Synthetic materials are an everyday component of modern healthcare yet often fail routinely as a consequence of medical‐device‐centered infections. The incidence rate for catheter‐associated urinary tract infections is between 3% and 7% for each day of use, which means that infection is inevitable when resident for sufficient time. The O'Neill Review on antimicrobial resistance estimates that, left unchecked, ten million people will die annually from drug‐resistant infections by 2050. Development of biomaterials resistant to bacterial colonization can play an important role in reducing device‐associated infections. However, rational design of new biomaterials is hindered by the lack of quantitative structure–activity relationships (QSARs). Here, the development of a predictive QSAR is reported for bacterial biofilm formation on a range of polymers, using calculated molecular descriptors of monomer units to discover and exemplify novel, biofilm‐resistant (meth‐)acrylate‐based polymers. These predictions are validated successfully by the synthesis of new monomers which are polymerized to create coatings found to be resistant to biofilm formation by six different bacterial pathogens: Pseudomonas aeruginosa, Proteus mirabilis, Enterococcus faecalis, Klebsiella pneumoniae, Escherichia coli, and Staphylococcus aureus.

Achieving Microparticles with Cell‐Instructive Surface Chemistry by Using Tunable Co‐Polymer Surfactants

“…By investigating the attachment of P. aeruginosa to a wide library of polymers, presented in a microarray format, Sanni et al found that there was no relationship with water contact angle, but those found to resist biofilm formation were relatively hydrophobic at 80–90 degrees. [ 5,8,9,23 ] To form a surfactant, we therefore require a hydrophilic partner for these monomers. Contact printing was used to produce a polymer microarray screen in order to determine the levels of hydrophilic monomer content that could be introduced into a surfactant composition, whilst retaining the desired level of biological performance.…”

“…[ 2,4–7 ] Recent methodological developments have facilitated the screening of a library of (meth)acrylate copolymers to identify a “hit” material that prevented biofilm formation by diverse bacterial pathogens including Pseudomonas aeruginosa , Staphylococcus aureus , and Escherichia coli . [ 5,8–10 ] The HT screening method used was based on polymer microarrays and has demonstrated utility for the discovery of biomaterials that have been used as coatings on existing medical devices. [ 5,10 ] However, most therapeutic delivery systems are not delivered as coatings, rather they exhibit 3D shapes.…”

Discovery of hemocompatible bacterial biofilm-resistant copolymers

“…We selected a series of weakly amphiphilic monomers from a library of 16 acrylates and methacrylates (Figure SI1, 1-16) that had previously been shown to resist biofilm formation when polymerized [ [27] , [28] , [29] , 36 ], and have also been shown to permit the permeation of antimicrobials for the creation of dual-functional anti-biofilm and anti-microbial coatings [ 37 ]. Since PEG based materials have been widely studied for their ability to prevent fouling by both blood proteins and host cells [ 22 ], monomers 1–16 were each combinatorially mixed with acrylate glycol monomers of varying chain lengths ( Figure SI1, A-D ) at volume ratios of 100:0 (homopolymers), 75:25, 50:50, 25:75 and 0:100 and copolymerized.…”

Inkjet based 3D Printing of bespoke medical devices that resist bacterial biofilm formation

“…This work has uncovered a series of findings that point towards the reliable manufacturing of cellinstructive structures via IJ3DP. With the advances in high throughput technologies, materials libraries offering diverse functions are becoming widely available [21][22][23]37] . It is not trivial, however, to go from an idealized screening approach to materials usable within a manufacturing setting.…”

“…A biofilm prevention strategy reduces the evolutionary pressures that drive the development of antimicrobial resistance. The biofilm surface coverage on polymer samples was reduced by 99% compared with those on silicone rubber for diverse multi-antibiotic resistant pathogens including P. aeruginosa, S. aureus Escherichia coli, Klebsiella pneumoniae, Enterococcus faecalis and Proteus mirabilis [22,23] . Here, we present a novel approach that shows how the candidate materials identified from such a screen can be adapted to create formulations suitable for IJ3DP and demonstrate that these formulations are effective in vitro and in vivo in a foreign body infection model.…”