Hydrogels are hydrophilic, three-dimensional polymeric networks prepared through chemical or physical conjugation. Hydrogels are recognized for their tunable properties, specifically through changes in the backbone of the polymers, such as 1) modifying the number of hydrophobic chain lengths, 2) adding or removing cleavable linkages, 3) varying reactive-end groups, 4) increasing or decreasing the weight percent of the hydrogel, and 5) combining two or more hydrogel networks into one, namely creating an interpenetrating network. We synthesized and characterized on- and off-demand, dissolvable hydrogels for use as burn wound dressings, polypectomy bandages, and vascular occlusion devices, and within interpenetrating networks. The hydrogels are composed of PEG-based crosslinkers, and PEI-based hyperbranched macromers which were prepared in high yields. In context of burn wound dressings, there is an unmet need for an adherent dressing with ease of removal, such as a dissolvable hydrogel dressing. In a model of in vivo porcine burn wounds, our hydrogel shows superior burn healing relative to traditional dressings such as sterile gauze pad and non-adherent foam dressings. When our hydrogel was removed, no newly formed tissue adhered to the dressing, and immunohistochemical stains exhibit improved inflammation and necrosis. When our hydrogel was used as an in vivo polypectomy sealant, we observed ease of application and adhesion to the colon, despite peristalsis. In in vitro studies, we observe no migration of bacteria through the hydrogel. As a vascular occlusion device, our hydrogels withstand an ex vivo burst pressure of up to 440mmHg on average, over 3x that of arterial pressure. Furthermore, we prepared an interpenetrating network from two hydrogel formulations both using SN2 chemistry with tunable mechanical properties. The hydrogel formulations highlighted in this work vary in gelation, mechanical properties, swelling, dissolution, and adhesion based on the structure of the polymer and reactive groups. These hydrogels represent a future direction in wound dressings and sealants as they prevent bacterial migration into an open wound, adhere to tissue, provide a moist wound environment, demonstrate structure-function relations allowing for tunable mechanical properties, and are biocompatible. / 2022-03-10T00:00:00Z

The potential of magnetic nanoparticle-vesicle assemblies (MNP-V) as remote controlled drug delivery platforms capable of inducing cellular responses under magnetic stimuli has been previously demonstrated in the Webb group at the University of Manchester. To create these magnetoresponsive nanomaterials biotin-avidin and Cu-histidinyl multivalent recognition were employed. This thesis describes an exploration of the potential of thiol-thioester exchange reactions (leading to native chemical ligation, NCL) to create magnetoresponsive materials, which potentially have applications in biomedicine. Firstly, iron oxide magnetic nanoparticles have been synthesised using a thermal co-precipitation method followed by chemical modification with sulfhydryl motifs for use as smart biomaterials. Knowing that the behaviour and reactivity of nanoparticles is highly influenced by their physicochemical properties, a thourough characterisation of these particles has been obtained. Secondly, during this project, several thioester derivatives have been synthesised that can be incorporated into the membranes of 800 nm liposomes. Among these, the spectrophotometric properties of synthetic lipid 38 allowed the investigation of trans-thioesterification rates with cysteinyl functionalities, both in solution and at the phospholipid membrane interface of liposomes. Product identification has been achieved using mass spectrometry and 1H-NMR spectroscopy. Finally, the conditions required to induce the release of a dye (e.g. 5(6)-CF) from MNP-V upon exposure to an AMF pulse have been established. Aurintricarboxylic acid (ATA), a general inhibitor of nucleases has been investigated as interesting payload due to its fluorescent and anti-viral properties.