Project 442766

The bypass procedure in the heart or legs and more preferably placement of a stent to either bypass or reopen arterial blockages saves lives. The bypass consists of harvesting a nonessential vessel and 'plumbing' it in around the blockage. Reconstruction can be achieved by harvesting a tissue segment complete with feeding artery, capillary bed and draining vein, (angiosome), and transplanting, again by 'plumbing' the vessels of these tissue flaps to vessels to the region of repair. Attempts to regrow blood vessels or indeed functional vascularised tissue segments to negate the need for graft harvest have been based on the premise that recapitulating normal anatomy will provide a functional analogue. While there have been some impressive demonstrations of potential, the central issue preventing an improvement in options for patients is the inability to regenerate complete vascular systems, (angiosomes). The main focus of prior research has been on arterial regeneration or in getting arteries to sprout new vessels. Attempts to grow new transplantable tissue in the body have focussed on using vein grafts that shortcut (anastomose) the arterial and venous systems that sprout new vessels that in turn are used to regenerate skin and bone. We recently challenged the dogma that new growing tissues require an arterial blood supply and instead considered the intact venous system as a potential regenerative source. We found that without being cut or transplanted, native veins could be induced to sprout profusely by placing a biomaterial around them and that unprecedented amounts of new bone could be grown on these new vessels and then transplanted as flaps. This proposal will explore the regenerative potential of blood vessel walls to grow bone and develop mature new angiosomes. The focus will be on developing minimally invasive approaches, reproducibility and acceleration of the process we have demonstrated as well as determine practical limits of the approach