Biofilms and biocompatibility: discovering alternative targets for preventing biomaterial-associated infections

Abstract

Medical implants are increasingly being utilised to either restore function after injury or disease. This has presented two main challenges that threaten long-term implant performance. First, biomaterials pose as a substantial risk for bacterial infections and as each implant procedure has an innate risk of infection, the number of biomaterial-associated infections keeps rising. Second, the foreign body response induced by the implant can result in undesired fibrotic encapsulation of implants. This work focused on the influence of micrococcal nuclease (Nuc1). Whether its activity on biofilm formation can be modulated by biomaterial hydrophobicity in vitro as well as the role it plays in biofilm formation both in vivo. Likewise, this project investigated the prospects of utilizing polymer coating to prevent bacterial adhesion and modulate the foreign body response. Results indicated that in vitro, biofilms could grow in the presence of Nuc1 activity. Also, Nuc1 and solid surface hydrophobicity influenced biofilm 3D-architecture in Chapter 2. In Chapter 3, Histological analysis showed that Nuc1 stimulates S. aureus to form biofilms, the presence of which extended neutrophil extracellular trap formation up to 13 days after mesh implantation. In Chapter 5 poly-N-isopropylmethacrylamide nanogel coatings prevented severe biofilm formation on surgical meshes while Chapter 6 showed that poly(ester amides) inhibited S. aureus growth and biofilm formation. Furthermore, Chapter 6 showed that poly(ester amides) promoted better tissue replacement with less fibrosis than poly(lactide-co-glycolides). The major implications of this study are that targeting Nuc1 activity could be a novel strategy in preventing biomaterial-associated infections and that poly(ester amides) are more biocompatible than poly(lactide-co-glycolides).