Soft amphiphilic biomaterials for antibacterial applications

Doctoral thesis, 2024

The growing threat of antimicrobial resistance (AMR) has highlighted the urgent need for innovative approaches to combat bacterial infections, particularly those associated with biomaterials used in medical devices. When bacteria colonize the surface of a biomaterial, persistent infections can arise, leading to patient suffering and placing a significant burden on the healthcare system. As traditional antibiotics become increasingly ineffective, developing new antibacterial materials and smarter strategies for using existing antibiotics is crucial in preventing biomaterial-associated infections and curbing the spread of AMR. Amphiphilic biomaterials, with their capacity to integrate antimicrobial functionalities, offer a promising solution by enabling surfaces and delivery systems that not only kill bacteria upon contact, but also release antimicrobial agents in a controlled manner, enhancing their effectiveness while minimizing resistance development. This thesis explores the use of amphiphilic polymers to develop soft biomaterials such as hydrogels, elastomers, and composite materials with antimicrobial properties. Two distinct antimicrobial modification strategies were employed: surface modification with contact-killing antimicrobial peptides (AMPs) and controlled release of antimicrobial agents from the bulk of the material. Expanding on previous work of amphiphilic hydrogels functionalized with AMPs, this research expands the design of soft biomaterials using similar building blocks. AMP-functionalized hydrogel particles were utilized to create elastomer coatings with contact-killing properties, and their synergistic interactions with existing antibiotics were evaluated. Additionally, the structure-activity relationships of AMP-functionalized hydrogel sheets were explored, revealing how AMP structure influences antibacterial performance. The AMP-functionalized materials demonstrated excellent antibacterial activity against both Gram-positive and Gram-negative bacterial strains, including drug-resistant variants, and exhibited significant potential for synergism with existing antibiotics. The thesis also details the development of elastomer blends with drug-eluting capabilities and investigates amphiphilic polymer-based hydrogel nanocomposites incorporating carbon nanotubes for enhanced drug delivery. These findings contribute to the advancement of amphiphilic biomaterials with potential applications as antimicrobial surfaces and drug-eluting materials, while addressing key challenges posed by AMR.