Thesis
Development of a micropatterned hydrogel scaffold for the delivery of polarised photoreceptor cells in retinal regeneration therapies
- Abstract:
-
Photoreceptor degeneration is a leading cause of irreversible sight loss worldwide. In patients affected by conditions such as age-related macular degeneration or retinitis pigmentosa, progressive degeneration of the outer nuclear layer (ONL) is followed by progressive vision decline, ultimately leading to blindness. In end stage disease, despite the loss of the ONL, the remainder of the neuroretina structures remain largely intact. Consequently, cell therapies aiming to recreate the ONL could restore the visual circuitry. Recent preclinical studies in mouse models have shown great promise in restoring visually mediated behaviour following cone photoreceptor cell transplantation into the degenerated subretinal space. However, delivery of cells in a bolus injection leads to dissipation of the transplanted cell mass away from the intended target, effectively reducing the density of the transplanted cells. Furthermore, in healthy retinae, the polarity of photoreceptor cells enables effective support from the retinal pigment epithelium and functional interactions with the inner nuclear layer. In this work, hyaluronic acid-derived hydrogel scaffolds are micropatterned to achieve polarisation of photoreceptor cells in vitro ahead of transplant. The hydrogel scaffolds also act as a protective niche for the cells, effectively increasing transplanted cell density.
This thesis first describes the development of the manufacturing process for the patterned hydrogel scaffold. By combining two-photon polymerisation printing and casting techniques, microscale topological features were patterned into the hydrogel to achieve basal-apical polarisation of photoreceptor cells in the z-direction. Secondly, biocompatibility of the optimised material formulation is established both in vitro and in vivo, including in murine models of degeneration. Finally, murine and hESC-derived photoreceptor cells were successfully cultured in the patterned hydrogel scaffold. Taken together, these findings highlight the potential of the developed hydrogel scaffold in augmenting established cell therapies by improving photoreceptor cell density and polarisation prior to transplant into the subretinal space of degenerated retinae.
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Authors
Contributors
+ Stevens, MM
- Institution:
- University of Oxford
- Division:
- MSD
- Department:
- Physiology Anatomy and Genetics
- Role:
- Supervisor
+ Pearson, RA
- Institution:
- King’s College London
- Role:
- Supervisor
+ Rosetrees Trust
More from this funder
- Funder identifier:
- https://ror.org/04e3zg361
- Grant:
- PhD2024\100005
- Programme:
- PhD Plus
- DOI:
- Type of award:
- DPhil
- Level of award:
- Doctoral
- Awarding institution:
- University of Oxford
- Language:
-
English
- Keywords:
- Subjects:
- Pubs id:
-
2374573
- Local pid:
-
pubs:2374573
- Deposit date:
-
2026-02-05
- ARK identifier:
Terms of use
- Copyright holder:
- Thomas FF Fernandez Debets
- Copyright date:
- 2025
- Rights statement:
- The copyright of this thesis rests with the author and is made available under a Creative Commons Attribution Non-Commercial No Derivatives license. Researchers are free to copy, distribute or transmit the thesis on the condition that they attribute it, that they do not use it for commercial purposes and that they do not alter, transform or build upon it. For any reuse or redistribution, researchers must make clear to others the license terms of this work.
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