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Novel nanofunctionalized self-sterilizing polymer coatings for biomedical implants

Seminar by Sania Ibragimova, Lund Univiversity.

Abstract
Two million fracture-fixation devices are inserted annually into human patients in the US and the demand for biomedical implants is rapidly increasing. Since 5% of these become infected, bacterial infections associated with biomedical implants present a severe problem. Bacteria colonize the implant surface, forming antibiotic-resistant biofilms. As it is difficult to treat these chronic infections with systemic antibiotic therapy, other solutions are necessary. A lot of research has been focused on designing antimicrobial implant surface coatings. These can be divided into two categories- biopassive and bioactive. Biopassive coatings prevent bacterial and protein adhesion to the implant, averting biofilm formation. Bioactive coatings contain macromolecules, which actively kill bacteria.  However, purely biopassive or purely bioactive coatings have been shown to be ineffective on a long-term basis.

In this thesis, the antimicrobial efficiency of four candidate polymers with a biopassive poly(L-lysine)-g-poly(ethylene glycol) (PLL-g-PEG) scaffold covalently end-modified on each PEG chain with biocide molecules, which provide a bioactive function, has been studied. Two of the biocide molecules were quaternary ammonium compounds (QACs) covalently linked to a short (C12) and a long (C18) alkyl chain respectively. One biocide molecule lacked a QAC, containing only a short (C12) alkyl chain. QACs have previously been shown to be effective bioactive coatings, but never before been used with a biopassive linker. A novel biocide comprising pyrimidine functionality was also tested. 

The study was primarily based on interactions of the antibacterial polymer surfaces with unilamellar lipid vesicles with a diameter of approximately 100 nm. The vesicle membranes were made up of Escheria coli total lipid extract to mimic an E. coli membrane. PEG(2000)-PE and PEG(5000)-PE were incorporated into the vesicles, acting as LPS mimics. These were used to study the effect of steric repulsion due to LPS on the polymer-bacterium interaction. Lastly vesicles containing LPS from E. coli Rd mutants were tested. Supplementary bacterial studies have been done on a genetically modified E. coli strain, AAEC191A, which is a fimbriae knock-out.