Multi-layer approaches to scaffold-based small diameter vessel engineering: A review

Cardiovascular disease is one of the leading causes of death in the world. A characteristic symptom of cardiovascular disease is occlusion of vessels. Once vascular occlusion occurs there is a critical need to re-establish flow to prevent ischemia in the downstream tissues. In the most advanced cases, flow is re-established by creating a secondary flow path around the blockage, bypass grafting. For large diameter applications, synthetic conduits are successfully implanted, however in small diameter applications re-occlusion occurs and there is a critical need for new vascular grafts. There are many strategies and approaches that are being employed to design an effective and successful vascular graft. However, to date, there are no clinically available small diameter vascular grafts that are consistently successful in vivo long term (> 7 years). As an effort to develop a successful graft there are several tissue engineering approaches: cell sheets, synthetic and natural biomaterial platforms, and decellularized extracellular matrices that are being investigated. While each area has its advantages, scaffold-based approaches are among the most widely studied. Scaffold based approaches are extensively studied due to tailorability and the availability of synthetic and natural polymers. Within the area of scaffold-based approaches, biomimicry has become an increasingly studied area, and structural biomimicry is one of the many approaches. The focus of this review paper is to analyze scaffold-based approaches. Particularly the advantages and disadvantages of using multi-layer scaffold-based approaches to engineer conduits for small diameter applications.