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Frontier research in arterial fibre remodelling for vascular disease diagnosis and tissue engineering

Periodic Reporting for period 3 - FibreRemodel (Frontier research in arterial fibre remodelling for vascular disease diagnosis and tissue engineering)

Reporting period: 2018-09-01 to 2020-02-29

Each year cardiovascular diseases such as atherosclerosis and aneurysms cause 48% of all deaths in Europe. Arteries may be regarded as fibre-reinforced materials, with the stiffer collagen fibres present in the arterial wall bearing most of the load during pressurisation. Degenerative vascular diseases such as atherosclerosis and aneurysms alter the macroscopic mechanical properties of arterial tissue and therefore change the arterial wall composition and the quality and orientation of the underlying fibrous architecture. Information on the complex fibre architecture of arterial tissues is therefore at the core of understanding the aetiology of vascular diseases. The current proposal aims to use a combination of in vivo Diffusion Tensor Magnetic Resonance Imaging, with parallel in silico modelling, to non-invasively identify differences in the fibre architecture of human carotid arteries which can be directly linked with carotid artery disease and hence used to diagnose vulnerable plaque rupture risk.
Knowledge of arterial fibre patterns, and how these fibres alter in response to their mechanical environment, also provides a means of understanding remodelling of tissue engineered vessels. Therefore, in the second phase of this project, this novel imaging framework will be used to determine fibre patterns of decellularised arterial constructs in vitro with a view to directing mesenchymal stem cell growth and differentiation and creating a biologically and mechanically compatible tissue engineered vessel. In silico mechanobiological models will also be used to help identify the optimum loading environment for the vessels to encourage cell repopulation but prevent excessive intimal hyperplasia.
This combination of novel in vivo, in vitro and in silico work has the potential to revolutionise approaches to early diagnosis of vascular diseases and vascular tissue engineering strategies.
To-date, high resolution imaging of ex vivo tissue has yielded considerable insights into the role of various constituents in arteries for maintaining the health of these vessels. Diseased vessels will now be imaged in the next phase of the project, with a view to developing key biomarkers of arterial disease that can be detected non-invasively.
Magnetic resonance imaging of ex vivo arterial tissue has shown the capabilities of DTI for analysing the intact microstructure of arteries and potential of such imaging to act as a biomarker for disease in arteries.
A small angle light scattering (SALS) system has been used to investigate arterial fibre growth and remodelling in vitro in response to mechanical stimuli and subsequently used to explore the degradation of arterial tissues under various strain conditions. The knowledge gained from this research work has implications for understanding cardiovascular disease progression and could also aid in the design and optimisation of next generation medical devices, including tissue engineered arteries.
In addition, numerical models of arteries been developed which can simulate damage accumulation and arterial remodelling which will be critical for medical device development.
Finally, porcine vascular smooth muscle cells and mesenchymal stem cells have been seeded on decellularised arteries where the structure has been fully characterized. The influence of strain and structure on the cell growth is currently being fully analysed and will enable optimisation of the scaffolds structure for tissue engineering applications.
This research is undoubtedly ‘high-gain’ in that it has the potential to transform the way cardiovascular diseases are currently diagnosed and treated. It should enable earlier diagnosis and better treatments with optimised bypass grafts that have better long-term outcomes. Ultimately therefore, the outputs from this project should yield significant social and economic benefits both nationally and internationally.