Optimisation of a novel hydrogel for the treatment of cerebral aneurysms
Brady, Sarah (2018) Optimisation of a novel hydrogel for the treatment of cerebral aneurysms. PhD thesis, Dublin City University.
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Approximately 1-6% of adults have a cerebral aneurysm. Treatments include clipping and coiling; however, over 20% of coiled aneurysms recur. A novel bioactive glass-alginate hydrogel has been optimised to fill the aneurysm and prevent recurrence.
For successful aneurysm embolization, the hydrogel must be injectable and set in situ, as well as meeting other design requirements, including; injectability, strength, adhesiveness, radiopacity and cytocompatibility.
The hydrogel was optimised by examining the effect alginate concentration, chemical composition and molecular weight has on the hydrogel’s properties. The glass was acid washed which improved homogeneity of the hydrogel and reduced glass agglomeration. The glass and GDL content were optimised and resulted in a hydrogel with a higher compressive strength compared to in situ gelling alginates reported in the literature. The addition of EDC and NHS improved the adhesive strength of the hydrogel without the need for cell attaching peptides. In vitro analysis showed cells can adhere and proliferate in direct contact with the hydrogel and its eluent. Proliferation was dose dependent and likely caused by silica ions and gluconic acid released. Although endothelial cells attached to the surface of the hydrogel, this was minimal. Platelet adhesion to the hydrogel was also marginal. The hydrogel was sterilised and radiopacity was improved, but with a loss in compressive strength. In vivo analysis indicated that issues occur in delivering this material into an aneurysm, though this hydrogel can be effectively used as an embolization treatment that supports the formation of a neointima layer.
This work highlights the influence each component has on the hydrogel’s properties. Although this hydrogel was optimised for the treatment of cerebral aneurysms, the hydrogel is highly tuneable and would be suitable for a range of embolic applications. This bioactive in situ gelling hydrogel would also be suitable for tissue engineering and therapeutic drug delivery.
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