Bioengineering strategies for the treatment of peripheral arterial disease

Peripheral arterial disease (PAD) is a progressive atherosclerotic disorder characterized by narrowing and occlusion of arteries supplying the lower extremities. Approximately 200 million people worldwide are affected by PAD. The current standard of operative care is open or endovascular revascularization in which blood flow restoration is the goal. However, many patients are not appropriate candidates for these treatments and are subject to continuous ischemia of their lower limbs. Current research in the therapy of PAD involves developing modalities that induce angiogenesis, but the results of simple cell transplantation or growth factor delivery have been found to be relatively poor mainly due to difficulties in stem cell retention and survival and rapid diffusion and enzymolysis of growth factors following injection of these agents in the affected tissues. Biomaterials, including hydrogels, have the capability to protect stem cells during injection and to support cell survival. Hydrogels can also provide a sustained release of growth factors at the injection site. This review will focus on biomaterial systems currently being investigated as carriers for cell and growth factor delivery, and will also discuss biomaterials as a potential stand-alone method for the treatment of PAD. Finally, the challenges of development and use of biomaterials systems for PAD treatment will be reviewed.