title: Furthering the understanding and 3D printing of dipeptide based low molecular weight hydrogels
Creators: name: Hill, Max John Samuel
Publisher: name: University of Glasgow
Year: 2024

description: Hydrogels produced from Low Molecular Weight Gelators (LMWGs) are an extremely versatile class of material, with a myriad of applications. However, many aspects of these materials are still not well understood. These gels can be formed via a range of methods, yet are inherently fickle in their formation, with minute differences within the gelation processes often causing significant changes to the properties of the final materials produced. As such, some important variables during gelation can be overlooked and are assumed to be insignificant, which is not always the case. Even for those variables that are shown to have an effect, this does not necessarily apply to similar low molecular weight gels formed via different gelation triggers. This Thesis will explore some additional considerations for low molecular weight gels, whilst further developing their suitability for 3D printing towards biomedical applications.

First, we demonstrate the successful 3D printing of two N-protected dipeptide based low molecular weight hydrogels in tandem to produce multi-layered 3D printed gel samples. Each gel differs in mechanical properties. Thus, through oscillatory rheology, we show changes to the overall sample mechanical properties depending on the number and ordering of the different printed gel layers. These findings were compared to non-printed equivalent multi-layered gel samples. Whilst inherently stiffer, the non-printed gel samples displayed the same trends in mechanical properties as the printed gels. We then explored the borders between separately printed gels via confocal microscopy and determined a lack of interface, with printed strips of gel remaining discrete and maintaining clear boundaries. This separation was highlighted through confocal microscopy experiments incorporating multiple different fluorescent dyes.

Secondly, we probe the impact of imposed spatial constraints on two different low molecular weight hydrogels. Gels were produced using either a solvent-switch or pH gelation trigger within different sized vessels and their localised mechanical properties compared via cavitation rheology. These were compared to differences in network microstructure observed by confocal microscopy. Solventtriggered gels displayed differences both in network microstructure and localised mechanical properties when formed in different sized vessels, whilst pH triggered equivalent gels did not. The former possesses a more compartmentalised microstructure of the underlying gelator network whilst the latter is instead underpinned by a more uniform network. These network differences align with the different responses to imposed spatial constraints between the two differently triggered gels. This study was expanded to gels formed in non-uniform vessels with smaller and larger portions, the results of which further confirmed initial observations.

Finally, we explore the surface of different supramolecular hydrogels for any potential differences in the underlying gelator network here. As an initial step towards better understanding the application of needle-induced cavitation rheology to low molecular weight gels, needle puncture experiments were performed on solvent and pH triggered gels. These initially alluded to a difference in the gelator network at the gels surface. Through confocal microscopy we observed changes within fibre alignment and density within the microstructure close to the surface of these gels. However, in subsequent oscillatory rheology and nanoindentation experiments we saw no difference in the mechanical properties. These observations were confirmed by follow up puncture data, which confirmed initial surface related data to be an instrument artefact.