Report

Teaser, summary, work performed and final results

Periodic Reporting for period 1 - FibreRemodel (Frontier research in arterial fibre remodelling for vascular disease diagnosis and tissue engineering)

Teaser

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...

Summary

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.

Work performed

A considerable amount of ex vivo imaging has been done showing the capabilities of DTI for analysing the intact microstructure of arteries. The imaging work done to-date has been published in three conference abstracts and two posters, one which was awarded the silver prize at the European Society for Magnetic Resonance in Medicine and Biology. A draft journal paper is in preparation and close to submission ready, whilst data has been obtained for at least another two journal papers which will be submitted over the coming months.
An improved constitutive model has been developed which incorporates damage and remodelling which will be critical for medical device development. The remodelling algorithm now includes 3D dispersion and remodelling to the optimum angle and optimum dispersion value. It is very sensitive to geometrical and load changes in the vessel. The model development has been presented at three national conferences and has been accepted for an oral presentation at the upcoming European Society of Biomechanics conference. This model is currently being written up for publication in a journal article.
Porcine vascular smooth muscle cells and mesenchymal stem cells have been seeded on decellularised arteries where the structure has been fully characterized using a novel collagen binding probe (CNA35). The influence of strain and structure on the cell growth is currently being fully analysed in order to enable optimization of the scaffolds structure for tissue engineering applications.

Final results

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.