View metadata, citation and similar papers at core.ac.uk brought to you by CORE provided by Elsevier - Publisher Connector INVITED REVIEW Biomaterials in the development and future of vascular grafts Lian Xue, MD, PhD,a and Howard P. Greisler, MD,a,b,c Maywood, Ill Recent developments in the field of tissue engineering have re-invigorated the quest for more suitable biomaterials that are applicable to novel cardiovascular devices, including small-diameter vascular grafts. This review covers both commercially available and relevant newly developed experimental materials, including elastic polymers (polyurethane), the biodegradable and bioresorbable materials, and the naturally occurring materials, focusing on their potential applications in the development of future vascular substitutes. (J Vasc Surg 2003;37:472-80.) The search for vascular substitute materials has thus far cular conduit. The emergence of tissue-engineering been a half-century endeavor.1 The initial failure of materials technology has made the development of a novel biologi- such as metal, glass, ivory, silk, and nylon brought 2 important cally viable vascular substitute feasible, and it may prove to criteria into focus: thrombogenicity and durability. Research be the ultimate solution for small-diameter vascular graft- was thus directed at inert materials that minimally interact ing. The purpose of this review is to highlight currently with blood and tissue. Polyethylene terephthalate (PET, Da- used and experimental biomaterials and their potential cron) and expanded polytetrafluoroethylene (ePTFE) are the applications in the development of future vascular grafts, products of this research and are currently the standard bio- focusing on those used for conventional open vascular materials of prosthetic vascular grafts. Examined by means of reconstructions. decades of use, both Dacron and ePTFE grafts have been shown to perform well at diameters Ͼ6 mm, but neither CURRENT MATERIALS material has been suitable for small-diameter (Ͻ4 mm) As aforementioned, the 2 standard polymers used for applications. Thus, finding a solution for small-diameter vascular grafts in clinical practice are Dacron and ePTFE. bypass grafting has become a major focus of attention. The Both PET and PTFE molecules are highly crystalline and mid- to long-term failure of existing synthetic grafts is hydrophobic, the 2 properties that prevent the polymers essentially caused by unfavorable healing processes, namely from hydrolysis. The hydrophobicity of the polymer has incomplete endothelialization and myointimal hyperplasia important implications in predicting surface interactions (IH). Seeking completely non-reactive substances is likely with blood and tissue. unrealistic. Optimizing tissue-biomaterial interactions to Dacron. PET was first introduced in 1939. DuPont elicit desirable results is thus a major emphasis of research. further developed it and patented its widely known Dacron Various modifications have been applied to Dacron and fiber in 1950.2 Vascular grafts made from Dacron were first ePTFE grafts to improve their function. Elastic polymers implanted by Julian in 1957 and DeBakey in 1958.1 have been used in the manufacture of compliant grafts on Clinically available Dacron grafts are fabricated in ei- the basis of the notion that compliance mismatch between ther woven or knitted forms. The multifilament Dacron the synthetic graft and native artery may contribute to IH. threads in woven grafts are fabricated in an over-and-under Biodegradable polymers can constitute a temporary scaf- pattern, which results in very limited porosity and minimal fold through which tissue ingrowth in vivo eventually re- creep of the finished graft. Knitted grafts are made with a places the prostheses and leave a complete biological vas- textile technique in which the Dacron threads are looped to create greater porosity and radial distensibility. The velour From the Department of Surgerya and the Department of Cell Biology, technique that extends the loops of yarn on the surfaces of b Neurobiology, and Anatomy, Loyola University Medical Center, and the fabrics has been used in an attempt to increase tissue Surgical Service, Hines VA Hospital.c Competition of interest: nil. incorporation. A crimping technique is used to increase the Reprint requests: Howard P. Greisler, MD, Loyola University Medical flexibility, distensibility, and kink-resistence of textile Center, Department of Surgery, 2160 South First Ave, Maywood, IL grafts. Prosthetic rings or coils are applied to the external 60153 (e-mail: [email protected]). surface of the grafts as external support to resist kinking and Copyright © 2003 by The Society for Vascular Surgery and The American possible mechanical compression. Association for Vascular Surgery. 0741-5214/2003/$30.00 ϩ 0 The high porosity of the knitted graft necessitates pre- doi:10.1067/mva.2003.88 clotting as a means of preventing transmural blood extrav- 472 JOURNAL OF VASCULAR SURGERY Volume 37, Number 2 Xue and Greisler 473 asation. Gelatin (Vascutek, Renfrewshire, Scotland), colla- untreated ePTFE graft of 56%, 46%, and 42%, respective- gen (Boston Scientific, Oakland, NJ), and albumin (Bard ly.19 The significance of heparin bound to synthetic grafts Cardiovascular, Billerica, Mass) are used to seal knitted will be further discussed in this review. Dacron graft pores. The gelatin and collagen in the Vas- Expanded polytetrafluoroethylene. PTFE was pat- cutek and Boston Scientific grafts are cross-linked by low ented by DuPont in 1937 as Teflon. Because of its partic- concentrations of formaldehyde, a method that results in a ular relatively inert characteristics, it was considered to be weak linkage that allows the gelatin or collagen to be an ideal electrical insulator.2 Its medical use began with its degraded in the body in Ͻ2 weeks.3,4 Bard uses glutaral- application in artificial heart valves in the early 1960s. In dehyde to cross-link albumin, and the albumin is absorbed 1969, Gore patented expanded ePTFE (Gore-tex), which in 2 months.5 is the material used in vascular grafts. The expanded poly- Dacron has a good stability and can persist for more mer is manufactured by means of a heating, stretching, and than 10 years after implantation without significant deteri- extruding process that produces a microporous material oration. However, knitted Dacron grafts have been prone more supportive of firm tissue adhesion. to dilate when implanted into the arterial environment, The PTFE molecule is biostable, and the graft made more because of fabrication technique than the polymer from it does not undergo biological deterioration within itself.6,7 Direct etiological association between graft dila- the body. The surface of the graft is electronegative, which tion and the later clinical complications has been rare.8 minimizes its reaction with blood components. ePTFE Other than this, there are no clinical differences grafts in grafts are manufactured by means of stretching a melt- complications and graft patency between woven and knit- extruded solid polymer tube, which then cracks into a ted grafts in their use as aortoiliac bypass grafts.9 Five-year non-woven porous tube. The characteristic structure of patency rates are 93% for aortic bifurcation grafts,10 but ePTFE is a node-fibril structure in which solid nodes con- only 43% for above-knee femoropopliteal bypass grafts,11 nect through fine fibrils, with an average internodal dis- and even lower for below-knee grafts. tance of 30 ␮m for a standard graft. Blood and tissue reactions to implanted grafts start Like Dacron grafts, ePTFE grafts perform well as aortic immediately after the restoration of circulation. The first substitutes, with a 5-year primary patency rate of 91% to step is a dynamic protein adsorption/desorption to syn- 95%.10,17 When used for femoropopliteal bypass grafting, thetic material surfaces, known as the Vroman effect,12 the 3- and 5-year patency rates are only 61%20 and 45%,11 followed by platelet adhesion, inflammatory cell infiltra- respectively, whereas the autogenous vein grafts have 5- tion, and endothelial cell (EC) and smooth muscle cell and 10-year cumulative patency rates of 77%21 and 50%, (SMC) migration.13,14 A coagulum containing fibrin, respectively.22 platelets, and blood cells builds up during the first few The initial host response to ePTFE grafts is similar to hours to days and stabilizes in a period of 6 to 18 months, that of Dacron grafts.13-15 A fibrin coagulum or amor- forming a compacted layer.15 The histological characteris- phous platelet-rich material develops in a time sequence tics observed within Dacron grafts is a compact fibrin layer that is similar in both materials. Lack of luminal surface on the blood-contacting surface and densely packed for- cellular coverage can be found at the midgraft region years eign body giant cells between the outer layer of the graft after human implants.23-25 In the outer wrap-reinforced wall and surrounding connective tissue capsule. The fibrin graft, the wrap limits the infiltration of the cells from layer within the midgraft remains acellular, regardless of perigraft tissue and leaves acellular fibrin matrix inside the whether the grafts are woven or knitted. An external velour graft wall.15 The densely fabricated wrap is manufactured surface permits more extensive and firmer incorporation of on the outer surface of some of the Gore-tex grafts as a the graft into surrounding tissue, but the function of an reinforcement to the graft wall. This wrap was beneficial in internal