- Novel antibacterial strategies to combat biomaterial-associated infection
M.D. de Jong
- Award date
- 27 September 2017
- Number of pages
- Document type
- PhD thesis
- Faculty of Medicine (AMC-UvA)
The use of medical devices has grown significantly over the last decades, and has become a major part of modern medicine and our daily life. The risk of infection is a significant problem with any inserted or implanted foreign body material, and is the number one cause of failure of implanted biomaterials. These so-called biomaterial-associated infections (BAI) are mainly caused by Staphylococcus aureus and Staphylococcus epidermidis. This thesis describes the development and characterization of novel antimicrobial agents and delivery systems, and their effectiveness in the prevention of BAI and other difficult-to-treat biofilm infections. The first strategy is based on a direct contact-killing approach. We describe the design and synthesis of a thin layer hydrogel with covalently attached synthetic antimicrobial peptides (AMPs) stabilized against proteolytic degradation. Another strategy to prevent BAI is the controlled release of antimicrobial agents, like chlorhexidine or synthetic AMPs, from a surface coating. All synthetic AMPs developed within this thesis have great potential for clinical application. Release of OP-145 was able to prevent S. aureus osteomyelitis in rabbits. The newly developed synthetic peptides, i.e. SAAP-145, SAAP-148, SAAP-276 and TC19, proved to have broad spectrum activity including activity against highly dangerous multi-drug resistant pathogens, to prevent biofilm formation, and to have in vivo activity, either in preventing biomaterial-associated or wounded skin infections. The results of the studies described in this thesis provide more insight in the pathogenesis of BAI and present novel prevention options in the fight against difficult-to-treat biofilm infection caused by multidrug-resistant pathogens.
Thesis (complete) (Embargo up to and including 27 September 2019)
Chapter 6: Development of SAAP-148 as topical treatment against drug-resistant bacteria, persisters and biofilms (Embargo up to and including 27 September 2019)
Chapter 7: Controlled release of LL-37-derived synthetic antimicrobial and anti-biofilm peptides SAAP-145 and SAAP-276 prevents experimental biomaterial-associated Staphylococcus aureus infection (Embargo up to and including 27 April 2018)
Chapter 8: TC19, a novel thrombocidin-1-derived antimicrobial peptide, eradicates multi-drug resistant Staphylococcus aureus as well as Acinetobacter baumannii in experimental skin infection (Embargo up to and including 27 September 2019)
Chapter 9: Selective laser melting porous metallic implants with immobilized silver nanoparticles kill and prevent biofilm formation by methicillin-resistant Staphylococcus aureus (Embargo up to and including 27 February 2019)
Dankwoord (Permanent embargo)
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