Atherosclerosis remains a serious source of morbidity and death despite advances in preventive measures and pharmacological therapeutics. Nearly 700,000 vascular surgical procedures are performed annually in the United States along with several hundred thousand peripheral and coronary angioplasties. Prosthetic bypass grafts and, more recently, arterial stents and other endovascular prostheses have been utilized in association with these reconstructive procedures.
Although large diameter vascular grafts (> 6 mm internal diameter) have been successfully developed from polymers such as polytetrafluoroethylene (PTFE) and polyethylene terephthalate, the fabrication of durable small diameter prostheses (< 6 mm internal diameter) remains unsolved. Furthermore, while prosthetic bypass grafting can be performed in the infrainguinal position with reasonable short-term success, within 5 years 30% to 60% of these grafts will fail. It is recognized that the adverse events leading to the failure of many vascular prostheses are related to maladaptive biological reactions at the blood-material and tissue-material interface. In response to these problems, and particularly thrombosis of the small caliber prosthesis, grafts and stents have been coated with albumin, heparin, or prostacyclin analogues, which inhibit the clotting cascade and platelet reactivity, or with relatively inert materials, such as polyethylene oxide. Despite promising early reports, these strategies have yet to produce a small diameter prosthesis with acceptable clinical performance characteristics. Opportunities at the interface of biology, biomolecular engineering, and materials science, as well as mechanical/chemical engineering offer new strategies to solve this challenge.
Ongoing efforts in our group seek to determine the molecular features of collagen and elastin fiber analogues that influence the mechanical behavior and physiochemical properties of protein-based fiber networks. Elastin and collagen analogues are produced by biosynthetic and chemical schemes and processed into fiber networks by a range of micro-fabrication techniques with or without associated cell populations. These engineered tissue structures provide with the means to study how micro-scale characteristics dictate the mechanical and biological responses relevant to the design of an arterial substitute under physiologically relevant conditions in vitro and in vivo.
Jordan SW, Haller CA, Sallach RE, Apkarian RP, Hanson SR, Chaikof EL. A recombinant elastin-mimetic coating on an ePTFE prosthesis reduces acute thrombogenicity in a baboon arteriovenous shunt. Biomaterials 2007; 28:1191-1197.
Caves JM, Kumar VA, Martinez AW, Kim J, Ripberger CM, Haller CA, Chaikof EL. The use of microfiber composites of elastin-like protein matrix reinforced with synthetic collagen in the design of vascular grafts. Biomaterials 2010; 27: 7175-7182.