NOVO

Novel approaches for prevention and degeneration of pathogenic bacteria biofilms formed on medical devices e.g. catheters

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 Obiettivo del progetto (Objective)

'Biofilms are bacterial communities encased in a self-produced hydrated polymeric matrix. An important characteristic of microbial biofilms is their innate resistance to the immune system and susceptibility to antibiotics. This resistance has made microbial biofilms a common cause of medical infections, and difficult-to-treat infections caused by colonized foreign bodies. The NOVO project aims at developing novel approaches to prevent and/or degrade biofilms on catheters elongating their usage in humans up to 10 days. Two complementary approaches for biofilm prophylaxis will be developed: A. Ultrasonic coating of Inorganic antibiofouling agents (process developed by partner BIU) based on a single step sonochemical process to: a) Produce metal fluorides or metal oxides (e.g. MgF2, ZnO) nanoparticles (NPs) and simultaneously b) Impregnate them as antibacterial factors on the catheters. c) Co-coating with bio-inert polymer layers (containing highly hydrophilic antifouling polyethylene glycol, zwitterionic moieties or sugar-groups) grafted onto NPs of adjusted size to the size of MgF2/ZnO NPs or directly onto MgF2/ZnO NPs; to form a hydrogel layer for the protection of the MgF2/ZnO antibiofouling activity. B. Bio/organic antibiofouling activation: 1) Novel coating for catheters based on radical catalyzed polymers to yield anti-bacterial activity. An enzymatic reaction will be applied on the phenolic compounds to generate phenolic radicals to be further polymerized on the catheter surface as an antibiofilm agent. 2) Develop and engineer Cellobiose Dehydrogenases (CDH) that actively oxidizes and degrades biofilms polysaccharides concomitantly producing stoichiometrically H2O2 as antibacterial agent. The enzymes will be coated on the catheters via a lubricant or by the Ultrasonic (US) process after their immobilization. Some novel CDH representatives already show very low activity on glucose which should be removed by further genetic engineering.'

Introduzione (Teaser)

Sonochemical processes prevent biofilms

Descrizione progetto (Article)

Biofilm-contaminated urinary catheters result in annual costs that exceed 400 million US dollars and increase the risk for emergence of multidrug-resistant bacteria. Pseudomonas aeruginosa and Staphylococcus aureus are the most common microbes in hospital settings that are multidrug resistant.

Different approaches have been attempted to prevent biofilm formation that include biological mechanisms and impregnation of medical devices with anti-microbial agents but they proved inefficient.

The EU-funded http://www.fp7-novo.eu (NOVO) project has exploited the low-cost, single-step, eco-friendly ultrasound (US) for inhibition of biofilm formation to produce novel anti-microbial coatings and materials. For coatings, researchers explored the efficacy of inorganic nanoparticles (NPs) like zinc oxide and magnesium fluoride (MgF2) as well as organic polymers and enzymes.

Scientists successfully coated inorganic particles onto catheters with MgF2 showing over 70% inhibition of biofilm formation. The entire sonochemical process for catheter coating took less than 30 minutes. Besides retaining biocompatibility, the catheter coatings were unaffected by sterilisation with gamma-radiation and ethylene oxide. Importantly, the coated catheter properties complied with regulatory requirements.

Coating of silicone catheters with organic polymers successfully reduced Pseudomonas aeruginosa and Staphylococcus aureus bacterial biofilm formation by over 50%. Modification conditions for the organic solvents were also optimised.

Coating catheters with enzymatically polymerised phenolic compounds yielded excellent results. Tests demonstrated over 80% anti-microbial activity in several bacterial species. Besides this, phenolic nanocapsules (e.g. epigallocatechin gallate nanocapsules (EGCG NCs)) were also coated onto catheters under varying conditions to optimise performance. Use of sulfobetaine methacrylate (SBMA) with phenolic NCs significantly improved biofilm inhibition.

In parallel, scientists immobilised enzymes like cellobiose dehydrogenase (CDH), amylase and acylase on catheter surfaces. CDH, acylase and amylase coatings also proved effective in reducing P. aeruginosa and S. aureus biofilm formations. Future work will focus on evaluating and optimising their anti-biofilm efficiency, toxicity, biocompatibility and longevity.

Commercialisation of NOVO products and techniques for coating medical devices such as implants and urinary catheters promises to cost-effectively and significantly reduce hospital-acquired infections. Besides improving healthcare quality and patients' quality of life, this will also boost the job market as well as European economy.