The BioMimics 3D stent is available under CE Mark only and is not approved in the United States.

This 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 substantially improve clinical outcomes.

BACKGROUND

Charles Thomas Stent, an English dentist, was appointed 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 manage 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 Stents
Stents 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 considered 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 endovascular interventions, and early attempts to use nondedicated stents failed.1,2 Stents became slightly more sophisticated, as did physicians’ use of dual antiplatelet agents.3,4 Randomised trials demonstrated the superiority 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 addition, 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 revascularisation. 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 system, it is extremely important to maintain patency and reduce rates of reintervention.

Benefits of Swirling Flow
Arteries 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 development 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 identified that restenosis also occurs in areas of abnormal flow and that high wall shear stress is protective.8-12

Problems With Stenting the SFA
The 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 vessel 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 biomechanical 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 constraints of the adductor canal into the less restrained popliteal artery. At this juncture, there are extreme deformations, 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 perforation, 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 morphology. 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 development 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 vasoprotective 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, all conventional straight stents, no matter how flexible, tend to straighten blood vessels, which reduces curvature and any naturally 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 centerline 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 helical 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 instent 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, fatiguetesting equipment. At that junction, there is a sudden transition from an externally constrained SFA to a relatively free popliteal artery. This environment was reproduced in vitro by placing a cylindrical constraint over a portion of the stent. Stents between 120 and 150 mm long from multiple manufacturers were evaluated during compression 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.

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 common 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 angiography confirmed that the BioMimics 3D stent imparts curvature to the diseased artery (Figure 8). Unlike drug elution from stents and balloons, the imposition of arterial 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

SUMMARY

Conventional, 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 generation 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 controlled trial, the clinical advantages of the BioMimics 3D stent over conventional straight stents have been demonstrated.

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

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