de Almeida Lins, Karina
(2025)
Development of anti-biofilm polymer coatings for neonatal feeding tubes.
PhD thesis, University of Nottingham.
Abstract
Feeding tubes are among the most used medical devices in neonatal intensive care and usually remain in place for many days. Most likely via frequent handling or from the contact with the infant’s oropharynx, these tubes easily become contaminated by microbes that develop into biofilms. Such events are associated with feeding intolerance, adverse gastrointestinal colonisation with harmful bacteria, and ultimately systemic infection, which can affect premature infants with severe illness or death. Aiming to reduce the infection risk associated with feeding tubes in this population, this thesis describes the development of novel biofilm-resistant polymer coatings for polyurethane neonatal feeding tubes.
The coatings were formulated by exploring three acrylate/methacrylate monomers with previously demonstrated biofilm-inhibiting properties: ethylene glycol dicyclopentenyl ether acrylate (EgDPEA), cyclododecyl methacrylate (CyDMA) and isobornyl acrylate (IBNA). Each monomer was co-polymerised with diethylene glycol methyl ether (DEGMA), and the optimal co-polymer ratios - poly(EgDPEA-co-DEGMA) 75:25, poly(CyDMA-co-DEGMA) 60:40, and poly(IBNA-co-DEGMA) 60:40 - were determined through mechanical stress testing and surface imaging, demonstrating satisfactory flexibility for coating feeding tubes.
The anti-biofilm efficacy of the coatings was assessed using fluorescent-tagged Pseudomonas aeruginosa, Staphylococcus aureus, and Escherichia coli in vitro. Laser scanning confocal microscopy revealed substantial biomass reduction on the coated tubes after 24 hours: 81–95% for P. aeruginosa, 62–73% for S. aureus, and 54–92% for E. coli.
Time-of-Flight Secondary Ion Mass Spectrometry (ToF-SIMS) analysis of the tubes following exposure to infant formula revealed the formation of a conditioning film that altered the original surface properties of the tubes. Lipid species - including fatty acids, phosphatidylcholines, and acylglycerols - were predominant and organized into micelle-like structures, with hydrophobic tails oriented inward and polar heads outward, resembling milk fat globules. These surface modifications reduced the contrast in bacterial behaviour between uncoated and coated surfaces. Poly(CyDMA-co-DEGMA) 60:40 coated tubes demonstrated the most effective performance under such conditions, achieving reductions of up to 58% for P. aeruginosa and 48% for S. aureus after 72 hours following exposure to infant formula. An in vitro feeding model replicating clinically relevant conditions - formula flow dynamics and viable cell recover - was developed to evaluate bacterial reduction by the tubes, which lowered E. coli and S. epidermidis colonies in flushed milk by 2.6-fold and 1.2-fold, respectively.
Overall, this thesis outlines the development and biological assessment of an improved medical device with potential to prevent biofilm formation on feeding tubes and infection among high-risk preterm infants, while exploring interactions between bacteria, polymer surfaces and infant formula.
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