Development of antibacterial medical devices by coupling 3D printing and drug repurposing

Device-associated infections are a major healthcare challenge as they are responsible for high disease burden in critically ill patients. In this doctoral thesis project, we have developed drug-eluting antibacterial catheters to prevent catheter-related infections. Niclosamide (NIC), originally an antiparasitic drug with anti-staphylococcal activity, was incorporated into the polymeric matrix of thermoplastic polyurethane (TPU) via solvent casting, and catheters were fabricated using hot-melt extrusion technology. Similarly, based on Ink jet printing technology, polymeric inks containing niclosamide, were developed to coat polyethylene catheters. Both antibacterial approaches will release niclosamide in a controlled and sustained way, thus exerting its antimicrobial effect leading to the prevention device-associated infections. The mechanical and physicochemical properties of the devices ere studied. Moreover, the antibacterial efficacy of NIC-loaded catheters was validated with an in vivo biomaterial-associated infection model using a methicillin-susceptible and methicillin-resistant strain of S. aureus. The released NIC from the produced catheters reduced bacterial colonization of the catheter as well as of the surrounding tissue. In summary, the NIC-releasing catheters prevented implant colonization and reduced the bacterial colonization of peri-catheter tissue by methicillin sensitive as well as resistant S. aureus in a biomaterial-associated infection mouse model and has good prospects for preclinical development.