Abstract
During aortic aneurysm formation, the balance between matrix synthesis and degradation in the vessel wall is disrupted. Both genetic and haemodynamic factors contribute to excessive degradation; however, pathological flow-driven stress, which affects the endothelium and the underlying matrix synthesising cells, is often underestimated. This project aims to build in silico and in vitro models that mimic physiological luminal and interstitial shearing forces on vascular cells within tissue-mimicking hydrogels. By underpinning in vitro experiments with mathematical models, we aim to identify transmural shear force contributions to cell behaviour, and ultimately create disease models that can stratify patients for aneurysm risk using non-invasive imaging techniques.
References
1 Lust ST, Hoogland D, Norman MDA, Kerins C, Jowett GM, Yu TTL, Xu Z, Yan Z, Marciano D, da Silva RMP, Dreiss CA, Lamata P, Shipley RJ, Gentleman E (2021) “Selectively cross-linked tetra-PEG hydrogels provide mechanical strength with limited impact on diffusivity.” Special issue on ‘Advanced Biomedical Hydrogels’. ACS Biomaterials Science & Engineering. In press.
2 Lust ST, Shanahan C, Shipley RJ, Lamata P, Gentleman E (2021) “Design considerations for engineering 3D models to study vascular pathologies in vitro.” Acta Biomaterialia. doi: 10.1016/j.actbio.2021.02.031
3 Jowett GM, Norman MDA*, Yu TTL*, Arévalo PR, Walters NJ, Hoogland D, Lust S, Read E, Niazi U, Foyt DA, Zabinski T, Lord GM, Dreiss CA, Hilborn J, Danovi D, Evans ND, Bozec L, Oommen OP, Lorenz CD, da Silva RMP, Neves JF†, Gentleman E† (2021) “ILC1 drive intestinal epithelial and matrix remodelling.” Nature Materials 20: 251-9. doi: 10.1038/s41563-020-0783-8 *These authors contributed equally. †Joint corresponding authors; equal contribution. Front cover article with accompanying News & Views: LeSavage & Heilshorn “Defined matrices bring IBD to 3D” doi: 10.1038/s41563-020-00904-1
4 Corral Acero J, …, Lamata P (2020) “The ‘Digital Twin’to enable the vision of precision cardiology” European heart journal 41 (48), 4556-4564. Doi: 10.1093/eurheartj/ehaa159
5 R Coy, G Al-Badri, C Kayal, C O’Rourke, P Kingham, JB Phillips, RJ Shipley, 2020. Combining in Silico and in Vitro Models to Inform Cell Seeding Strategies in Tissue Engineering. Journal of the Royal Society Interface (doi.org/10.1098/rsif.2019.0801)