Antimicrobial Polysaccharides for Biomedical Applications

Polysaccharides are widely used across various fields owing to their biological properties, biodegradability, and availability. Through various modification techniques, their properties can be tailored for specific applications. Chitosan, derived from deacetylated chitin, is particularly appealing in the biomedical sector due to its antimicrobial properties in acidic conditions. The polymer's amino groups become protonated in acidic environments, imparting a positive charge. This cationic charge is a crucial factor for antimicrobial activity, as most pathogens possess a net-negative surface charge and are thus susceptible to the positive charge of protonated chitosan.  Introducing quaternary ammonium groups to the polysaccharide backbone establishes a permanent positive charge. In this thesis, two distinct quaternary ammonium moieties, [2-(acryloyloxy)ethyl]trimethylammonium chloride (AETMAC) and glycidyl trimethylammonium chloride (GTMAC), were incorporated into chitosan to investigate the potential of these derivatives as antiviral and antibacterial agents. These chitosan derivatives demonstrated significant promise as antimicrobial agents, particularly in biomedical applications, where there is an urgent need for new biobased solutions to combat infections and antibiotic resistance. This study evaluated and optimized the physiochemical and biological properties of the AETMAC and GTMAC derivatives. Due to differences in chemical structure and polymerization processes, the derivatives exhibited vastly different properties. Here, AETMAC functionalization is based on radical polymerization, while GTMAC is directly grafted onto the chitosan structure as a result of a nucleophilic ring-opening reaction of the epoxide moiety. AETMAC-functionalized derivatives showed superior antimicrobial properties and were further used to develop biocompatible chitosan-based composite materials.  Quaternary chitosan was combined with other polysaccharides and synthetic polymers to develop biocompatible hydrogels for medical purposes, especially wound healing applications. By optimizing the constituents of the composite, 3D printable and injectable hydrogels were obtained, featuring cross-linked polymeric networks based on physical and chemical cross-linking. In vitro biocompatibility assays of the hydrogels showed no acute cytotoxicity, addressing a common issue associated with higher degrees of quaternization. These findings underscore the potential of quaternary chitosan in developing biocompatible and effective antimicrobial materials for biomedical applications.