Periodic Reporting for period 4 - FibreRemodel (Frontier research in arterial fibre remodelling for vascular disease diagnosis and tissue engineering)
Reporting period: 2020-03-01 to 2022-02-28
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.
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.