Development of a tri-layered electrospun scaffold for potential use in small diameter tissue engineered vascular grafting

Abstract

Tissue engineered vascular grafts (TEVGs) may have the potential to replace saphenous vein for multiple small diameter (<6mm) coronary artery bypass grafts, which exhibit poor long-term patency, often leading to repeat surgeries. Currently, there are no clinically used TEVGs due to inferior short-term patency rates when compared with autologous saphenous vein. One of main reasons for early TEVG failure is thrombus formation, which is attributed to a sparse or absent luminal endothelial monolayer. Inadequate host cell infiltration and angiogenesis are also thought to contribute to short and long term TEVG failure. The aims of this PhD project were to: (i) determine the feasibility to create a tri-layered electrospun scaffold, combining aligned and random topographies of nano- and macro-size fibres where necessary to: (i) enhance endothelial cell attachment and promote a luminal endothelial morphology (ii) promote a physiologically representative vascular smooth muscle cell (VSMC) morphology (iii) promote cellular infiltration and host remodelling.
This work demonstrated that electrospinning is a versatile technique, which can be used to create seamless multi-layered tubes with layer specific topographies. Endothelial cell attachment was improved for nano-scaled fibre diameters, and endothelial cell orientation was found to be affected by the underlying cell culture substrate topography. The phenomenon of cell orientation in relation to the underlying substrate topography was also observed for smooth muscle cells. Furthermore, this work presented evidence that it is possible for macrophages to transdifferentiate into smooth muscle cells.
In conclusion, this thesis presents an investigation into the optimisation and creation of a tri-layered tube for use a TEGV by using specific electrospun topographies to enhance cellular attachment and promote an aligned morphology. It also demonstrates the potential for TEVGs to be populated with autologous blood from patients.

Date of Award	28 Nov 2019
Original language	English
Awarding Institution	University of Bristol
Supervisor	Sarah J George (Supervisor) & Raimondo Ascione (Supervisor)