Development of a Transplantation Platform Technology Applicable for Improving Graft Survival in the Brain
Final Report Abstract
This work builds upon our previous work that showed the cells can survive in the absence of oxygen for several days or a week, however, as soon as glucose is removed, they die very quickly. So, whilst hypoxia has been shown in grafted cells, we predicted that a paucity of glucose is the predominant driver of cell death post-transplantation. To overcome this hurdle facing transplantation efficacy, we developed glucose releasing biomaterials, with the goal of their future use in rescuing cells from ischemic death posttransplantation. Although sustained release could be achieved from macroscale formulations, unfortunately, when scaled down, the microscale spheres showed a rapid burst release of the encapsulated glucose. However, these were shown to be non-toxic and to rescue SH-SY5Y cells (model dopamine neurons) from oxygen-glucose deprivation. As we were using very short monomer chain lengths to encapsulate the glucose, it looks like a different form of encapsulation will be necessary for sustained release in future studies. One factor that we had not forecasted was high viscosity of the PAE macromers, making the use of microfluidic devices technically not feasible. The liquid monomer diethylene glycol diacrylate was used for microsphere formation as it had shown good release on the macroscale so was deemed a suitable candidate for microsphere formation. Whilst we had envisaged that the release rate would be faster in the microscale systems, we had hoped that at least a release of seven days could be achieved. Unfortunately this was not the case.
Publications
- Cryogel Scaffolds for Regionally Constrained Delivery of Lysophosphatidylcholine to Central Nervous System Slice Cultures: A Model of Focal Demyelination for Multiple Sclerosis Research, Acta Biomaterialia, 2019, 97, 216-229
D. Eigel, L. Zoupi, S. Sekizar, P. B. Welzel, C. Werner, A. Williams, B. Newland
(See online at https://doi.org/10.1016/j.actbio.2019.08.030) - Biomaterial Based Strategies to Reconstruct the Nigrostriatal Pathway in Organotypic Slice Co-Cultures, Acta Biomaterialia, 2021, 121, 250-262
B. Ucar, J. Kajtez, B. M. Foidl, D. Eigel, C. Werner, K. R. Long, J. Emnéus, J. Bizeau, M. Lomora, A. Pandit, B. Newland, C. Humpel
(See online at https://doi.org/10.1016/j.actbio.2020.11.035) - Selective Vulnerability of Inhibitory Networks in Multiple Sclerosis, Acta Neuropathalogica, 2021, 141, 415-429
L. Zoupi, S. A. Booker, D. Eigel, C. Werner, P. C. Kind, T. L. Spires-Jones, B. Newland, A.C. Williams
(See online at https://doi.org/10.1007/s00401-020-02258-z)
