UK - Department for Business, Energy and Industrial Strategy
Potential of acellular biological scaffold coated with chemokines and cytokines as tissue engineered small artery grafts
Project Data Last Updated: 27/08/2020
IATI Identifier: GB-GOV-13-FUND--Newton-MR_T018208_1
Millions of coronary or peripheral artery bypass grafts are performed yearly worldwide by cardiac and vascular surgeons using patient's own veins from the leg (SVG) or synthetic grafts. However, >50% of these grafts get blocked after 5-10 years, with common infections at the harvesting sites and frequent hospital re-admissions. Patient's own arteries are used only in 1:5 cases due to shortage of available artery, despite >95% of these do not get blocked after 15 years. Using arterial grafts made in the lab provides hope for future patients. Our previous research suggests that implanting biological tubes made from pig or cow material into a pig graft experimental model leads to encouraging but sub-optimal results. This is an exciting development, but we need to improve the lining of the graft to reduce the occurrence of blockages. Our goal is to improve the grafts by coating the biological scaffolds with proteins able to attract cells and create a suitable lining which stops blockage by blood clots and cell growth. Our plan will allow us to achieve grafts more similar to real arteries which avoid the use of the patients own leg vein and induce the patients blood cells to create an optimal graft. This would pave the road to bringing this new technology to the bedside in 5-10 years, while saving large amount of resources to the health services and greatly improving patient's well-being and outcome.Objectives
The overall objective of the proposal is to determine whether an acellular biological scaffold coated with chemokines and cytokines enhances monocyte adhesion and differentiation into endothelial-like cells which provide a protective lining to the graft and thereby retards thrombosis and lumenal encroachment and improves graft performance. The creation of an acellular scaffold that avoids the harvesting of saphenous vein from the patients leg will shorten the surgical procedure, avoid discomfort and infection of the wound site and thereby improve patient outcome and the cost of the procedure. Moreover, the scaffold will induce in situ cell recruitment and differentiation which will avoid the need for ex vivo tissue engineering which is costly and time-consuming. The specific research objectives are to: i. Investigate monocyte recruitment to acellular scaffolds coated with MCP-1 and CX3CL1, (coated vs. uncoated xenogeneic pericardia or porcine intestinal submucosa extracellular matrix (SIS-ECM)) in a static in vitro and dynamic ex vivo flow system. ii. Examine pleiotrophin and TNF-alpha modulation of monocyte/macrophage differentiation into ECs in a static in vitro and dynamic ex vivo flow system. iii. Compare the outcome of the two coated acellular scaffolds to control uncoated scaffolds at 1-month after surgical implantation in a pig carotid artery model.
|Extending:||UK Research & Innovation|
|Funding:||UK - Department for Business, Energy and Industrial Strategy|
|Implementing:||University of Bristol|
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