Thesis
Evaluation of a collagen-based hydrogel as a delivery system for Parkinson’s disease therapeutics
- Creator
- Rights statement
- Awarding institution
- University of Strathclyde
- Date of award
- 2023
- Thesis identifier
- T16586
- Person Identifier (Local)
- 201789335
- Qualification Level
- Qualification Name
- Department, School or Faculty
- Abstract
- Parkinson’s disease (PD) is a neurodegenerative disorder that affects the dopaminergic neurons in the substantia nigra. Recently, cell therapy has emerged as a promising therapeutic strategy. To increase the cell viability, biomaterials are used to facilitate the cell deposition through injection. However, the existing delivery approaches have shown limited success in clinical translation. This thesis aims to evaluate a collagen hydrogel as a delivery system for therapeutics for PD. This is achieved with the following objectives. Firstly, the hydrogel usability for delivery to the central nervous system (CNS) was evaluated. A material characterisation was conducted, which showed that the mechanical properties of the hydrogel make it an appropriate system for CNS implantation. Additionally, the gelation time showed that the hydrogel will form fast enough once injected and will not diffuse to the surrounding tissue. Low swelling ratio was observed, a desirable characteristic for hydrogels delivered to the CNS. However, a high hydrogel mass loss was observed at body temperature and shear rate was shown to have an effect to the mechanical properties, as the hydrogels formed under shear appeared less stiff. This could impact the clinical translation, as injecting the hydrogel could alter its mechanical properties. Secondly, an investigation of the effect of the delivery device design on the flow of collagen during injection was carried out. The effect of the design was evaluated computationally, and it was shown that as collagen passes through the syringe to the needle, different forces are present, depending on the design. A tapered design with big needle diameter was indicated to be appropriate for collagen delivery. The next objective was the computational assessment of collagen injection to the striatum. The infusion to the brain tissue was evaluated using the biphasic solute method. An effect of infusion pressure and the needle tip to the distribution of resulting pressure and stress to the tissue was shown. A linear relationship between the infusion pressure and the resulting pressure and stress was observed, while their relationship with the needle diameter was nonlinear. Finally, the feasibility of a novel biomaterial-based method for the reconstruction of the nigrostriatal pathway was assessed. The feasibility to create a hydrogel tube, long enough to connect the substantia nigra to the striatum was shown. This research has provided further insight to the subject of biomaterial delivery to the CNS and has exhibited that the method of delivery of therapeutics is of pivotal importance for a successful clinical translation.
- Advisor / supervisor
- Kazakidi, Asimina
- Riches, Philip
- Resource Type
- DOI
- Date Created
- 2022
- Embargo Note
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