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An overview of the hemodynamic and biomechanical advantages of a biomimetic stent

designed for use in the SFA.

BY PROF. P.A. GAINES, MD

Biomimetic Stents and the Benefits of Swirling Flow

T his article describes how a clear understanding of nature’s ability to maintain healthy patent arteries has led to the development of a new generation of biomimetic stents that substan-

tially improve clinical outcomes.

BACKGROUNDCharles Thomas Stent, an English dentist, was appoint-

ed to the Royal Household in 1855 after his innovative work with dentures; in particular, he improved the compound used to take dental impressions. In a leap of imagination, Stent’s compound was used by a Dutch plastic surgeon, Johannes Fredericus Esser, to help man-age horrific facial wounds in the First World War. Esser used the material to stretch and stabilise skin grafts. This supporting mold was subsequently referred to as a stent, and the word is now generally used to describe a device that provides support.

Arterial StentsStents are principally used to improve the internal

lumen of a vessel before or after angioplasty. The use of stents has been widely successful, and they are now ubiquitous in the field of cardiovascular interventions. The majority of interventions in the coronary arteries are now stent based, and aortoiliac stenting is widely con-sidered to be part of the standard of care for occlusive disease. However, the superficial femoral artery (SFA) provides a much more challenging environment.

All Stents Are Not Made Equal The SFA is a difficult, hostile environment for endo-

vascular interventions, and early attempts to use non-dedicated stents failed.1,2 Stents became slightly more sophisticated, as did physicians’ use of dual antiplatelet agents.3,4 Randomised trials demonstrated the superior-ity of stenting over simple angioplasty, but still 12-month primary patency was low at 63% to 71%.3,4 At 2 years after implantation of the LifeStent (Bard Peripheral Vascular), the target lesion revascularisation (TLR) rate

was 22%, and after implantation of either the Dynalink or the Absolute stent (Abbott Vascular), TLR was 63%.

Patency and TLR rates are very important in terms of risks associated with reintervention and costs. For the patient, there is a clear link between loss of patency and recurrence of symptoms, and if further revascularisation is required, then the repeat intervention is unpleasant, costly, and exposes the patient to further risk. In addi-tion, the clinical outcome of reintervention is poor. For the health care system, the costs to manage peripheral artery disease (PAD) are substantial. In the United States, 12% to 15% of the population older than 65 years has PAD, accounting for 8 to 10 million people; this number will only increase with an aging population and rising prevalence of obesity and diabetes. The 2-year hospital costs of PAD are $7,000 per patient if they only have claudication, $10,400 if the patient has an amputation, and $11,700 if the patient previously had revascularisa-tion. The difference in costs between these groups is largely driven by the high costs of reintervention.5 It is apparent that, for both the patient and health care sys-tem, it is extremely important to maintain patency and reduce rates of reintervention.

Figure 1. Swirling flow in the aorta.

Courtesy of Imperial College, London.

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FEATURED TECHNOLOGY: BIOMIMICS 3D STENT

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Benefits of Swirling FlowArteries are nonplanar and three dimensional (3D) in

nature, and the effect produces swirling flow (Figure 1).6 Swirling flow creates high wall shear stress, which has been shown to be protective against both the develop-ment of atheroma and restenosis. A study published in Nature in 1969 noted that areas of high wall shear stress tend not to develop atherosclerosis.7 Later work identi-fied that restenosis also occurs in areas of abnormal flow and that high wall shear stress is protective.8-12

Problems With Stenting the SFAThe SFA has complex biomechanics, which makes stent

placement challenging. On knee extension, the SFA has a gentle open spiral shape. During knee flexion, the artery can shorten by forming a more helical pattern in the distal vessel (Figures 2A and B). Conventional straight stents placed in the SFA are less compliant than the normal ves-sel and do not accommodate this shortening. This results in additional vessel slack being transferred to areas of the artery adjacent to the stented segment. The biome-chanical incompatibility between a conventional straight stent and the artery can result in kinking and occlusion

(Figure 3).13-15 In addition, microtrauma and abnormal flow patterns at the junction between the stent and vessel can result in restenosis and atherosclerosis.13

The artery passes through the musculoskeletal con-straints of the adductor canal into the less restrained

Figure 2. Gentle curvature of the SFA with the knee extended

(A). With the knee flexed, the distal SFA adopts a helical pat-

tern to accommodate vessel slack (B).

Figure 3. CT angiogram from a cadaver showing the SFA

and popliteal artery before and after placement of a conven-

tional, straight nitinol stent. Before stent placement, arterial

shortening is accompanied by a natural increase in curvature

of the vessels. After stent placement, the vessel is more rigid

and can no longer accommodate the shortening. This results

in kinking of the artery below the stent.

A

B

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FEATURED TECHNOLOGY: BIOMIMICS 3D STENT

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popliteal artery. At this juncture, there are extreme defor-mations, including axial and radial compression, bending, and torsion. This extremely challenging, complex junction can impact the structural integrity of stents, resulting in strut fractures at rates of up to 25% at 1 year.16,17 These fractures may be associated with restenosis, arterial perfo-ration, false aneurysms, and distal embolisation. Given the anatomic complexity around the adductor hiatus and the complex mechanical loads placed upon a stent in this area on knee flexion, it is not surprising to find that vigorous exercise is a predictor of stent fracture.18

Local hemodynamics, including the ability to generate swirling flow, are strongly affected by the arterial morphol-ogy. Wall shear stress > 1.5 Pa appears to be protective against atheroma and restenosis, and low wall shear stress (< 0.5 Pa) is related to the development of atherosclerosis and restenosis.8,11 Unfortunately, the SFA possesses low wall shear stress under resting conditions (Figure 4).19 Conventional straight stents not only further reduce any natural curvature of the artery, but also have to persist in an environment that naturally is amenable to the develop-ment of restenosis and further atherosclerosis.

BIOMIMICRY AND HARNESSING THE ADVANTAGES OF SWIRLING FLOW

The Biomimicry Institute describes biomimicry as “an approach to innovation that seeks sustainable solutions to human challenges by emulating nature’s time-tested patterns and strategies.” Nature uses vessel curvature to

generate swirling flow, elevating wall shear stress to vaso-protective levels.

Recent stent designs are more flexible and seek to better match or mimic the natural curvature of the SFA; these are referred to as mimetic stents. However,

Figure 4. Computational fluid dynamics demonstrates that the swirling flow in the aorta and iliac arteries develops wall

shear stress in the “protective” range (> 1.5 Pa); however, in the SFA, the lack of swirling flow results in wall shear stress in the

“pathogenic” range (< 0.5 Pa). This correlates with the higher prevalence of atherosclerosis and increased restenosis rates fol-

lowing stent placement.

Figure 5. The BioMimics 3D stent.

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FEATURED TECHNOLOGY: BIOMIMICS 3D STENT

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all conventional straight stents, no matter how flexible, tend to straighten blood vessels, which reduces curvature and any natu-rally occurring swirling flow and potentially lowers the shear stress down to pathological levels.

The BioMimics 3D stent (Veryan Medical Ltd) is a true biomimetic stent that, by design, imparts curvature, generates swirling flow, and leads to a vasoprotective environment. The self-expanding stent is laser cut from a nitinol tube and has 3D helical center-line geometry set into the nitinol shape memory (Figure 5). It has an advanced technology–based design with repeating two crown units and specific connectors that allow both flexibility and the imposition of heli-cal geometry. The end three crowns

have gradually reducing radial force to improve the transition in profile from artery to stent, improve the flow characteristics, and reduce the risk of poor flow and low wall shear stress that might lead to in-stent restenosis.

Hemodynamic and Biomechanical Advantages of BioMimics 3D Versus Conventional Straight Nitinol Stents

The helical shape of the BioMimics 3D stent facilitates artery shortening during knee flexion and manages the arterial slack during knee flexion resulting in less kinking at the junction between stent and native vessel (Figure 6).

The ability of the BioMimics 3D stent to resist fracture caused by extreme forces at the junction between the adductor canal and popliteal artery was evaluated using custom-designed, fatigue-testing equipment. At that junction, there is a sudden transition from an externally constrained SFA to a relatively free popliteal artery. This envi-ronment was reproduced in vitro by placing a cylindrical constraint over a portion of the stent. Stents between 120 and 150 mm long from mul-tiple manufacturers were evaluated during com-pression in the environment to 1 million load cycles. This bench test demonstrated that the BioMimics 3D stent can withstand the highest level of axial compression without fracture when compared to the current commercially available conventional straight stents.

Figure 7. An angiogram of porcine common carotid arteries showing

the deformation that occurs after implantation of a stent with a helical

centerline (right) compared to the contralateral common carotid artery

containing a straight stent (left). Computational fluid dynamics again

demonstrates the high swirling flow and wall shear stress generated

by the helical centerline stent (A). Histology of explanted porcine com-

mon carotid arteries 4 weeks after implantation of helical centerline and

straight stents. The area of neointima is statistically significantly reduced

after implantation of the helical centerline stent (B).

A

B

Figure 6. A CT angiogram showing the maintenance of the natural curvature of the

popliteal artery below a BioMimics 3D stent (left) on knee flexion compared to the

kink in the popliteal artery below a conventional straight stent (right).

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FEATURED TECHNOLOGY: BIOMIMICS 3D STENT

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The gentle transition of the BioMimics 3D stent, from the gradually reducing radial force of the end three crowns of the stent and the native artery, is specifically designed to reduce microtrauma, abnormal localised flow patterns, and kinking that could otherwise lead to restenosis, new atherosclerosis, and occlusion.

Swirling flow is important in limiting restenosis. To test the effect on swirling flow, a straight stent and a helical centerline stent were placed in opposite com-mon carotid arteries in a porcine model.20 The study demonstrated that the BioMimics 3D stent is not only capable of deforming the native vessel into a helix, but also that the subsequent swirling flow significantly reduced the development of restenosis (Figures 7A and B).

The advantages of this biomimetic stent were tested in the MIMICS trial, a multicenter, prospective, randomised, core lab–controlled trial in which the BioMimics 3D stent was compared to a conventional straight stent (LifeStent) in 76 patients with symptomatic occlusive disease of the SFA. Conventional radiographs and angi-ography confirmed that the BioMimics 3D stent imparts curvature to the diseased artery (Figure 8). Unlike drug elution from stents and balloons, the imposition of arte-rial curvature is not transient but will continue to have benefit over restenosis and atherosclerosis in the long term. Compared to a straight stent, the BioMimics 3D stent had significantly improved primary patency at 2 years and significantly reduced clinically driven TLR between 1 and 2 years.21

SUMMARYConventional, straight, nitinol self-expanding stents

do not perform well in the SFA. Understanding the biomechanics of the SFA and the effects of swirling flow have led to the development of a new genera-tion of biomimetic stents. The BioMimics 3D stent has a unique design that imparts curvature to the vessel, similar to that seen in nature. In a randomised con-trolled trial, the clinical advantages of the BioMimics 3D stent over conventional straight stents have been demonstrated. n

Prof. P.A. Gaines, MD, is from Sheffield Hallam University in Sheffield, United Kingdom. He has disclosed that he is a consultant to Veryan Medical Ltd. Dr. Gaines may be reached at pgaines@outlook.com.

BioMimics 3D is manufactured by Veryan Medical Ltd.PAM 095 Issue 00

1. Chalmers N, Walker PT, Belli AM, et al. Randomized trial of the SMART stent versus balloon angioplasty in long superficial femoral artery lesions: the SUPER study. Cardiovasc Intervent Radiol. 2013;36:353-361.2. Krankenberg H, Schlüter M, Steinkamp HJ, et al. Nitinol stent implantation versus percutaneous transluminal angioplasty in superficial femoral artery lesions up to 10 cm in length: the femoral artery stenting trial (FAST). Circulation. 2007;116:285-292.3. Laird JR, Katzen BT, Scheinert D, et al. Nitinol stent implantation versus balloon angioplasty for lesions in the superficial femoral artery and proximal popliteal artery: twelve-month results from the RESILIENT randomized trial. Circ Cardiovasc Interv. 2010;3:267-276.4. Schillinger M, Sabeti S, Loewe C, et al. Balloon angioplasty versus implantation of nitinol stents in the superficial femoral artery. N Engl J Med. 2006;354:1879-1888.5. Mahoney EM, Wang K, Keo HH, et al. Vascular hospitalization rates and costs in patients with peripheral artery disease in the United States. Circ Cardiovasc Qual Outcomes. 2010;3:642-651.6. Caro CG, Doorly DJ, Tarnawski M, et al. Non-planar curvature and branching of arteries and non-planar flow. Proc R Soc Lond. 1996;452:185-197.7. Caro CG, Fitz-Gerald JM, Schroter RC. Arterial wall shear and distribution of early atheroma in man. Nature. 1969;223:1159-1160.8. Carlier SG, van Damme LC, Blommerde CP, et al. Augmentation of wall shear stress inhibits neointimal hyperpla-sia after stent implantation: inhibition through reduction of inflammation? Circulation. 2003;107:2741-2746.9. Caro CG. Discovery of the role of wall shear in atherosclerosis. Arterioscler Thromb Vasc Biol. 2009;29:158-161.10. Chiu JJ, Chien S. Effects of disturbed flow on vascular endothelium: pathophysiological basis and clinical perspectives. Physiol Rev. 2011;91:327-387.11. Malek AM, Alper SL, Izumo S. Hemodynamic shear stress and its role in atherosclerosis. JAMA. 1999;282:2035-2042.12. Qin F, Dardik H, Pangilinan A, et al. Remodeling and suppression of intimal hyperplasia of vascular grafts with a distal arteriovenous fistula in a rat model. J Vasc Surg. 2001;34:701-706.13. Arena FJ. Arterial kink and damage in normal segments of the superficial femoral and popliteal arteries abutting nitinol stents—a common cause of late occlusion and restenosis? A single-center experience. J Invasive Cardiol. 2005;17:482-486.14. Jonker FH, Schlosser FJV, Moll FL, Muhs BE. Dynamic forces in the SFA and popliteal artery during knee flexion. Endovasc Today. 2008;7:53-58.15. Zocholl G, Zapf S, Schild H, Thelen M. [Functional angiography of the arteries near the knee joint: consequences for stent implantation?] [Article in German]. Rofo. 1990;153:658-662.16. Davaine JM, Azema L, Guyomarch B, et al. One-year clinical outcome after primary stenting for Trans-Atlantic Inter-Society Consensus (TASC) C and D femoropopliteal lesions (the STELLA “STEnting Long de L’Artere femorale superficielle” cohort). Eur J Vasc Endovasc Surg. 2012;44:432-441.17. Scheinert D, Scheinert S, Sax J, et al. Prevalence and clinical impact of stent fractures after femoropopliteal stenting. J Am Coll Cardiol. 2005;45:312-315.18. Iida O, Nanto S, Uematsu M, et al. Effect of exercise on frequency of stent fracture in the superficial femoral artery. Am J Cardiol. 2006;98:272-274.19. Wood NB, Zhao SZ, Zambanini A, et al. Curvature and tortuosity of the superficial femoral artery: a possible risk factor for peripheral arterial disease. J Appl Physiol (1985). 2006;101:1412-1418.20. Caro CG, Seneviratne A, Heraty KB, et al. Intimal hyperplasia following implantation of helical-centreline and straight-centreline stents in common carotid arteries in healthy pigs: influence of intraluminal flow. J R Soc Interface. 2013;10:20130578.21. Zeller T. BioMimics 3D—advanced stent design: concept to randomised controlled trial. Presented at the Leipzig Interventional Course (LINC); January 30, 2014; Leipzig, Germany.

Figure 8. Plain radiographs demonstrating the curvature

imparted to the SFA in lateral (A) and anterior/posterior (B)

projection in a patient participating in the MIMICS trial.

A B