Development of tissue engineered blood vessel as vascular bypass graft

Vascular reconstructive surgery is a procedure that has multiple clinical applications to treat life-threatening cardiovascular disease. If an artery is blocked or damaged, a vascular surgeon may replace the damaged section with a graft where a healthy artery or vein from elsewhere in the body is used to bypass clogged vessels and restore blood flow. It is used to treat several conditions such as coronary heart disease and critical limb ischaemia where there is a severe shortage of blood flow to arms, legs or feet that can increase the risk of heart complications. It is also used to create vascular access for haemodialysis to ‘clean’ patients' blood in end-stage kidney disease. 

Ideally, healthy blood vessels will be taken from another part of the patient to be used as a graft. These grafts using the patient’s own blood vessels are known as autologous grafts.  However, many patients do not have suitable blood vessels due to extensive cardiovascular disease or have insufficient number of blood vessels for multiple/repeated surgeries. The shortage of autologous vascular grafts may then require the use of synthetic vascular grafts. These synthetic grafts, which work well for reconstruction of big arteries such as the aorta, are, however associated with high incidence of graft failure when used as substitutes for smaller vascular grafts including coronary bypass graft, lower limb bypass graft and arteriovenous graft for haemodialysis. This unmet clinical need stimulates research into vascular tissue engineering of small calibre vascular grafts. However, previous designs of synthetic tissue engineered blood vessels (TEBV) have failed to replicate the mechanical and functional features of natural blood vessels and have been associated with a high incidence of thrombosis, stenosis (narrowing of the veins) and aneurysm.

This project aims to develop cross-disciplinary approaches to fabricate a human cell-based TEBV that replicates the structure, mechanics and function of the natural artery which is known to be the best vascular candidate for bypass surgery. The proposed TEBV will provide a novel solution to the clinical shortage of autologous vascular bypass grafts and an innovative human vascular disease model for biomedical research and new drug development. It promises a potential new treatment for life-threatening vascular diseases and will particularly benefit older patients with poor healing capability and young children who require vascular implants that will “grow” with the body.

By the end of this project, it is expected that we will have a well validated human based TEBV that is ready for scaling up for large animal trials. Relevant aspects of the research will be published in academic journals and presented at international conferences. Other possible outcomes of this project may include new patents and new collaborations with the pharmaceutical industry.