Production of functionalised micro 3D printed superoxide dismutase mimetic devices by two photon polymerisation
O'Halloran, Seán
(2023)
Production of functionalised micro 3D printed superoxide dismutase mimetic devices by two photon polymerisation.
PhD thesis, Dublin City University.
Two-photon polymerisation (TPP) is a premier technique that can produce a wide variety of materials applied to chemistry, biology, and medical devices. The production of optics, microcircuits and micro-robots by TPP has also generated interest for its use in material sciences, bacterial sensing, scaffold development, and stem cell research. The majority of devices reported can be functionalised using a variety of chemistries including esterification, amidation, and thiolene-type reactions. However, the use of copper-catalysed azide-alkyne cycloaddition (CuAAC) reactions have not been widely employed. This thesis focuses on the treatment of reactive oxygen species (ROS)-mediated inflammatory conditions, through the development of superoxide dismutase (SOD) mimetic TPP microstructures as medical devices. SOD is a ubiquitous enzyme, responsible for the catalytic redox of superoxide and vital for the viability of the host. Inflammation is a multifaceted and complex response of the body to pathogenic or foreign body invasion, resulting in the up regulation of superoxide as a signalling molecule and antimicrobial factor. Typically, highly regulated inflammatory responses are resolved through set pathways, involving the degradation and removal of pro-inflammatory markers, removal of inflammatory cells, and epithelialisation to return tissues to homeostasis. However, chronic inflammation interventions include non-steroidal anti-inflammatories (NSAIDs) and cyclooxygenase (COX) inhibitors but their use is systemic, non-tissue specific, and can be detrimental to the healing process. In this thesis, SOD mimetic microstructures were designed through the CuAAC conjugation of azide-bearing Cu(II) chelating ligands with alkyne-modified acrylate monomers, which were employed in the development of novel resins. In their Cu(II) chelated state, these ligands act as potent SOD mimetics capable of detoxifying superoxide, a gateway ROS that contributes to chronic and acute inflammatory conditions. A series of micro-medical devices containing these SOD mimetics were printed and their anti-inflammatory properties were evaluated both in-vitro and in-celluo.