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Abstract

Despite the advancements in sterilization and aseptic techniques, bacterial infections associated with medical implants and devices have not been eradicated. Consequently, the utilization of antibiotic-based treatment has become the preferred approach due to its efficiency, rapidity, and versatility. Nevertheless, the overuse or misuse of antibiotics in the healthcare-related sector is a primary factor contributing to the emergence of antibiotic-resistant bacteria. The existence of such antimicrobial resistance has been demonstrated to result in a significant increase in surgical interventions, an elevated risk for medical complications and even an increased mortality rate. This situation has led to an urgent need to explore and develop alternative, efficient, antibiotic-free therapeutic options. A promising alternative approach involves the coating of medical devices and implants with antibacterial agents to combat bacterial infections. Despite the progress made in recent years, antibacterial coatings have not reached a complete protection against severe inflammation. This can be attributed, at least in part, to the "open-space" design of the current coatings, which expose surrounding cells and tissues to the released contents of the dying and dead bacteria. This thesis focuses on the design and development of two modular antibacterial systems, utilizing a "confined space" in which the bacteria are entrapped/engulfed, and subsequently eliminated, thereby protecting the surrounding tissue from bacterial fragments and the released bacterial toxins. The first approach involves the high-throughput formation of mechanically robust, highly porous polymer-based microcapsules. A careful selection of the polymers, solvents, pore-forming agents and the manufacturing process conditions was essential for the creation of stable biodegradable microcapsules with a porous polymer shell and an inner hollow cavity. The developed porous microcapsules demonstrated effective trapping properties for motile bacteria. Moreover, the functionalization of the capsule's shells with gold nanorods (AuNRs) facilitated the integration of a near-infrared (NIR) light-triggered bacteria-killing module into the porous microcapsules. It is important to note that the efficient killing of bacteria that are either entrapped within the microcapsules or in close proximity has been achieved. Due to the advanced mechanical stability and antibacterial properties, the developed polymer-based porous microcapsules have the potential to be implemented as an antibiotic-free coating on orthopedic implants. The second approach focused on engineering bioinspired phagocytotic-like antibacterial systems. In this regard, giant unilamellar vesicles (GUVs) have been selected as compartments for the uptake of bacteria in a target-specific manner. To this end, the GUV membrane has been functionalized with a bacteriophage-derived tail protein. Tail protein-mediated adhesion enabled efficient engulfment of targeted bacteria by the GUVs. Moreover, in order to equip the synthetic phagocytotic system with the NIR light-triggered bacteria-killing mechanism, the vesicle membranes were functionalized with AuNRs. With these properties, the developed bioinspired phagocytotic antibacterial system has the potential to be implemented as an antibacterial washing solution.