Bridging the Gap for Small-Diameter Vascular Grafts

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Science Translational Medicine  25 Jul 2012:
Vol. 4, Issue 144, pp. 144ec130
DOI: 10.1126/scitranslmed.3004620

Like a detour that bypasses a traffic accident, surgeons often reroute blood flow around a diseased segment of an artery using vascular grafts. The new conduit can be formed from a harvested artery from the patient or from a synthetic graft made of a nondegradable material such as polyester or teflon. An artificial conduit can be preferable because much of the vascular system in these patients is often diseased, but for small conduits of less than 5 mm in diameter, no synthetic or tissue-engineered vascular graft stays open and effective in maintaining blood flow. Now, Wu, et al. have developed a fast-degrading, synthetic graft that may work for replacing smaller diseased vessels and provide new treatment options for those in need of vascular substitutes.

Wu and colleagues designed a synthetic graft consisting primarily of a fast-degrading elastomer, poly-(glycerol sebacate). Using a salt-leaching fabrication process, they made a conduit with a highly porous wall. To prevent blood from leaking out of the pores in the material and to increase the graft strength, they used electrospinning (a process that uses high voltage to create very fine fibers) to create a tight mesh of polycaprolactone on the outside of the graft. The graft was then coated with the anticoagulant heparin so as to inhibit clotting and clogging of the pores. The result is a cell-free conduit that rapidly degrades in the body in ~3 months.

The authors implanted their synthetic conduit in rats to bypass the aorta and examined its remodeling over time. After 3 months, the synthetic graft had disappeared and left behind a neovessel formed of endogenous cells. Most important, the new tissue had similar composition and biomechanical properties to the native artery. In addition, the graft had been infiltrated with M2 macrophages, a cell type associated with constructive vascular remodeling and reduced inflammatory responses.

The work of Wu et al. is a departure from traditional tissue engineering: Their graft is designed to rapidly degrade and be taken over by native cells. This promising first step toward successful small-diameter vascular grafts will need to be tested in large animal models before these findings can be translated to human patients.

W. Wu et al., Fast-degrading elastomer enables rapid remodeling of a cell-free synthetic graft into a neoartery. Nat. Med., 24 June 2012 (10.1038/nm.2821). [Abstract]

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