Nanoscale Strategies: Treatment for Peripheral Vascular Disease and Critical Limb Ischemia

Peripheral vascular disease (PVD) is one of the most prevalent vascular diseases in the U.S. afflicting an estimated 8 million people. Obstruction of peripheral arteries leads to insufficient nutrients and oxygen supply to extremities, which, if not treated properly, can potentially give rise to a severe condition called critical limb ischemia (CLI). CLI is associated with extremely high morbidities and mortalities. Conventional treatments such as angioplasty, atherectomy, stent implantation and bypass surgery have achieved some success in treating localized macrovascular disease but are limited by their invasiveness. An emerging alternative is the use of growth factor (delivered as genes or proteins) and cell therapy for PVD treatment. By delivering growth factors or cells to the ischemic tissue, one can stimulate the regeneration of functional vasculature network locally, re-perfuse the ischemic tissue, and thus salvage the limb. Here we review recent advance in nanomaterials, and discuss how their application can improve and facilitate growth factor or cell therapies. Specifically, nanoparticles (NPs) can serve as drug carrier and target to ischemic tissues and achieve localized and sustained release of pro-angiogenic proteins. As nonviral vectors, NPs can greatly enhance the transfection of target cells with pro-angiogenic genes with relatively fewer safety concern. Further, NPs may also be used in combination with cell therapy to enhance cell retention, cell survival and secretion of angiogenic factors. Lastly, nano/micro fibrous vascular grafts can be engineered to better mimic the structure and composition of native vessels, and hopefully overcome many complications/limitations associated with conventional synthetic grafts.