Development of a micro-patterned hydrogel scaffold to guide photoreceptor polarization for treatment of macular degeneration
File(s)
Author(s)
El Laham, Raya
Type
Thesis
Abstract
One of the main causes of retinal degenerative diseases is irreversible loss of photoreceptors, which results in visual impairment and can lead to blindness. Current treatment options for photoreceptor degenerative diseases are limited, with most treatments focused on halting the progression of the disease and improving the quality of life of patients. The treatments that do provide some restoration of vision cannot provide the necessary sensitivity and resolution. Photoreceptor replacement therapies aim to deliver healthy photoreceptor cells to the damaged retina to replace those lost through degeneration. Recent studies have demonstrated that using biomaterial scaffolds to deliver photoreceptors can increase the survival, proliferation, integration, and migration of the transplanted cells in the host retina. Furthermore, patterned scaffolds have a demonstrated ability to polarize photoreceptors in vitro and improve the likelihood of forming synaptic connection with the host cell once transplanted, and thus increasing the possibly of restoring vision.
The main objective of this thesis was to develop a micro-patterned hydrogel scaffold with a defined geometry aimed at guiding the polarisation of photoreceptors. The hydrogel material was characterized to study the swelling, rheological, diffusion and degradation behaviours of the material, and to identify the optimal polymer concentration that produces the required physical properties. A method for fabricating the patterned scaffold was optimized to be well defined and reproducible. Using a high resolution two photon polymerisation printer, a highly defined negative print with columnar structures was fabricated. Extensive optimisation of the scaffold fabrication process was performed to successfully and repeatably produce the final scaffold in a semi-automated manner. Preliminary cell viability experiments were conducted on non-patterned hydrogels to examine the effect of these concentrations on cell survival in vitro.
The main objective of this thesis was to develop a micro-patterned hydrogel scaffold with a defined geometry aimed at guiding the polarisation of photoreceptors. The hydrogel material was characterized to study the swelling, rheological, diffusion and degradation behaviours of the material, and to identify the optimal polymer concentration that produces the required physical properties. A method for fabricating the patterned scaffold was optimized to be well defined and reproducible. Using a high resolution two photon polymerisation printer, a highly defined negative print with columnar structures was fabricated. Extensive optimisation of the scaffold fabrication process was performed to successfully and repeatably produce the final scaffold in a semi-automated manner. Preliminary cell viability experiments were conducted on non-patterned hydrogels to examine the effect of these concentrations on cell survival in vitro.
Version
Open Access
Date Issued
2022-06-18
Date Awarded
2024-02-01
Copyright Statement
Creative Commons Attribution NonCommercial Licence
License URL
Advisor
Stevens, Molly
Publisher Department
Materials
Publisher Institution
Imperial College London
Qualification Level
Doctoral
Qualification Name
Doctor of Philosophy (PhD)