De Luca, Maria (2022) Anti-infective medical devices:the employment of Host Defence Peptides identified in Human Apolipoprotein B. [Tesi di dottorato]

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Abstract

Introduction of medical devices in modern medical practise has significantly improved patients’ well-being. However, the employmentof these “foreign” devices into human body can also be associated with serious complications, among which biofilm-associated infections remain a major public health concern. The emergence and fast diffusion of antibiotic-resistant bacterial strains makes the management of such infections increasingly difficult. AntiMicrobial Peptides (AMPs), also named Host Defence Peptides (HDPs) because of their wide range of bioactivities, are small molecules present in all the living organisms. They are generally endowed not only with direct antimicrobial activity, but also with anti-biofilm,antifungal, antiviral, anticancer, wound healing, and immunomodulatory properties. Because of this wide range of properties and because they generally don’t lead to the development of multidrug resistance phenotype, they attracted considerable attention as an effective weapon to generate antimicrobial surfaces. The main aim of the present PhD Thesis has been the evaluation of the applicability of novel HDPs identified in human Apolipoprotein B to design infection-resistant medical devices. The attention has been focused on the functionalization of two kinds of medical devices, such as urinary catheters and contact lenses, with a selected ApoB-derived peptide. Polydimethylsiloxane (PDMS) polymer, generally employed to fabricate urinary catheters, and hydroxyethylmethacrylate (HEMA)hydrogel, the main component of commercial soft contact lenses, have been selected as prototypes materials for functionalization studies. In both cases, a physicochemical characterization of obtained functionalized material has been performed together with analyses of peptide loading and release from surfaces under test. Importantly, anti�infective properties and cytocompatibility of obtained functionalized surfaces have been also evaluated by using bacterial strains commonly associated to medical devices infections and proper eukaryotic cell lines simulating those generally in contact with medical devices. Altogether, obtained results open interesting perspectives to the applicability of ApoB-derived peptides to functionalize surfaces of biotechnological interest.

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