The development of a cell-free, biodegradable artery graft could lead to a transformative change in coronary artery bypass surgeries.
The new method, developed at the University of Pittsburgh, could give bypass patients a regenerated artery with no trace of synthetic graft materials left in the body within 90 days.
The work was led by principal investigator Yadong Wang, a professor in Pitt’s Swanson School of Engineering and School of Medicine’s Department of Surgery, who designed grafts that fully harness the body’s regenerative capacity. It was published in online in Nature Medicine highlights on 24 June.
According to a statement, this new approach is a philosophical shift from the predominant cell-centred approaches in tissue engineering of blood vessels.
‘The host site, the artery in this case, is an excellent source of cells and provides a very efficient growth environment,’ said Wang. ‘This is what inspired us to skip the cell culture altogether and create these cell-free synthetic grafts.’
Wang and fellow researchers, Wei Wu, a former Pitt postdoctoral associate, and Robert Allen, a PhD student in bioengineering, are said to have designed the graft with three properties in mind.
First, they chose a graft material — an elastic polymer called PGS — that is resorbed quickly by the body. Then, they examined graft porosity and selected parameters that allow immediate cell infiltration.
Wang’s team used a procedure developed by another team of Pitt researchers, wrapping the vascular graft with a fibrous sheath to trap the cells.
Finally, Wang and his fellow researchers employed heparin, a coating that reduces blood clotting and binds many growth factors.
‘The results were porous grafts that are suturable,’ said Wang. ‘And the rapid remodelling of the grafts led to strong and compliant new arteries. The extent of the changes in the grafts that occurred in just 90 days was remarkable.’
Wang and his colleagues are said to have made grafts as small as 1mm in diameter and monitored the graft’s transformation in vivo for three months.
Because the graft was highly porous, cells were able to penetrate the graft wall and mononuclear cells occupied many of the pores within three days.
Within 14 days, smooth muscle cells — an important blood vessel builder — appeared. At 28 days, cells were distributed more evenly throughout the graft. At 90 days, most inflammatory cells were gone, which correlated with the disappearance of the graft materials.
The artery was regenerated in situ and pulsed in sync with the host. Furthermore, the composition and properties of the new arteries are nearly the same as native arteries.
‘This report is the first that shows a nearly complete transformation of a synthetic plastic tube to a new host artery with excellent integration within three months,’ said Wang. ‘Most likely, the amount of time it takes to regenerate an artery can be further shortened as we refine the system.’