Low molecular weight hydrogels for cell culture and bioprinting

Wallace, Chloe May (2025) Low molecular weight hydrogels for cell culture and bioprinting. PhD thesis, University of Glasgow.

Abstract

Low molecular weight gelators (LMWG) are promising candidates for biomaterials due to their unique properties such as their reversibility and ability to hold large volumes of solvent. However, issues can arise when attempting to gel these materials under conditions acceptable for cell culture. In this thesis, the aim was to develop and comprehensively characterise a LMWG system at physiological pH. We employ a variety of techniques to investigate these materials across different length scales. By doing so, we have highlighted the significance of such characterisation when developing novel non-covalent biomaterials.

We outline how the dipeptide-based LMWG 2NapFF (diphenylalanine protected with a naphthalene group at the N-terminus) produces biocompatible hydrogels when crosslinked with ions present in cell culture media. We also explore the impact of heating and cooling the gelator solution prior to initiating gelation as well as the impact of adding PODS® (micron-scale proteins containing cargo molecules which are gradually released over prolonged peroids) to the system for functionalisation purposes. Our findings reveal that a heating and cooling cycle can be used to adjust the properties of the resulting network without changing the gelator itself. Moreover, it was found that PODS® had minimal effect on the properties of the hydrogel, indicating that they can enhance the bioactivity of the systems without altering the network structure. PODS

Furthermore, we compare the 2NapFF hydrogels previously discussed to a Ureidopyrimidinone (UPy) supramolecular hydrogel system, consisting of a monofunctional building block and bifunctional crosslinker species. We explored the effects of combining these two systems, both with and without the UPy crosslinker. Our results show that the assembly of the combined systems is primarily driven by the UPy component. Furthermore, the UPy crosslinker plays a vital role in the self-sorting of the UPy and 2NapFF components. It was also revealed that for cells to adhere effectively, the bifunctional UPy subunit was crucial to produce a supportive network.

In the final experimental chapter, we investigate the potential of the 2NapFF hydrogels crosslinked with cell culture media as bioinks for extrusion-based 3D printing. Through optimisation of the printing process, it was demonstrated that the type of media used to trigger gelation directly impacted the printability of the systems. As a result, the samples that consistently formed self-supporting structures were selected for printing macrophage cells, which remained viable within the gel after 24 hours. Bioprinting macrophages can be used in applications such as immune system and tumour microenvironment modeling.

• Item Type: Thesis (PhD)
• Qualification Level: Doctoral
• Subjects: Q Science > QD Chemistry
• Colleges/Schools: College of Science and Engineering > School of Chemistry
• Supervisor's Name: Adams, Professor Dave
• Date of Award: 2025
• Depositing User: Theses Team
• Unique ID: glathesis:2025-84900
• Copyright: Copyright of this thesis is held by the author.
• Date Deposited: 17 Feb 2025 10:29
• Last Modified: 17 Feb 2025 10:30
• Thesis DOI: 10.5525/gla.thesis.84900
• URI: https://theses.gla.ac.uk/id/eprint/84900

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