Vascular diseases include aneurysms causing hemorrhage, atherosclerosis causing occlusion of blood vessels, vascular malformation, and tumors. Vessel occlusion or rupture of an aneurysm within the brain can result in stroke. Aneurysms fed by intracranial arteries can grow within the brain to a point where their size can also cause a stroke or the symptoms of a stroke, requiring surgery to remove the aneurysm, or other remedial intervention.
Occlusion of coronary arteries is a common cause of heart attack. Diseased and obstructed coronary arteries result in restricted blood flow in the heart which can lead to ischemia or necrosis. While the exact etiology of sclerotic cardiovascular disease is still in question, the treatment of narrowed coronary arteries is more defined. Surgical construction of coronary artery bypass grafts (CABG) is often the method of choice when there are several diseased segments in one or multiple arteries. Conventional open-heart surgery is of course highly invasive and traumatic for patients undergoing such procedures. Therefore, less invasive procedures that accomplish the same goals are highly desirable.
One alternative method of treatment involves the use of balloon angioplasty as a way in which to reopen the lumen of an occluded vessel. In this procedure a folded balloon is inserted via a catheter into a stenosed region that is either partially or fully occluding the vessel lumen. Inflation of the balloon physically expands the lumen, reopening the occluded region, and restoring normal or at least significantly improved blood flow through the vessel. Alternatively, occlusive atheromas may be cut from the inner surface, a procedure known as atherectomy. In both methods, a certain incidence of restenosis (resealing) occurs resulting in a loss of the benefit of the procedure, and potentially the need for additional rounds of therapy. Restenosis also results in reversion back to the original occluded condition, such that the vessel no longer conducts a normal flow volume, which can lead to ischemia or infarct depending on the particular location and function of the vessel in question.
A recent preferred therapy for repairing vascular occlusions involves placement of an expandable metal wire-frame (i.e. a stent) within the occluded region of a blood vessel in order to keep the lumen of the vessel open. Stents are generally delivered to the desired location within a vascular system by an intraluminal route, usually via a catheter. Advantages of the stent placement method over conventional vascular surgery include obviating the need for surgically exposing, removing, replacing, or by-passing the defective blood vessel, including heart-lung bypass, opening the chest and in some cases general anaesthesia.
When inserted and deployed in a vessel, duct or tract (all of which can be conveniently referred to as a vessel) of the body, for example, a coronary artery after dilation of the artery by balloon angioplasty, a stent acts as a prosthesis to maintain the vessel in an open state, thus providing a fluid pathway in the previously occluded vessel. The stent usually has an open-ended tubular form with interconnected struts as its sidewall to enable its expansion from a first outside diameter which is sufficiently small to allow the stent to traverse the vessel lumen and be delivered to a site where it is to be deployed, then expanded to a second outside diameter sufficiently large to engage the inner lining of the vessel for retention at that site. The stent may be expanded via the use of a mechanical device, for example a pressurizable balloon, or alternatively the stent may be self-expanding. Self-expanding stents can be manufactured at a to be deployed size, and then compressed to a smaller size to enable delivery, or may be manufactured from shape memory materials that are deformable to a memorized shape in response to an externally applied energy.
Usually a stent suitable for successful interventional placement should be hypoallergenic, or preferably non-allergenic, have good radio-opacity to permit radiographic visualization, free from distortion during magnetic resonance imaging (MRI), plastically deformable, resistant to vessel recoil, and be as thin as possible to minimize obstruction to blood flow (or other materials or fluids in vessels other than those of the cardiovascular system), and be relatively non-reactive in terms of eliciting thrombogenic responses.
The typical reaction when a foreign body is implanted in a body vessel is generally negative. Foreign bodies frequently cause an inflammatory response, and in the case of blood vessels, neointimal proliferation which results in narrowing and occlusion of the body vessel, obviating the benefit of the implant. As a result, both selection of the materials from which the stent is composed, as well as the design of the stent, play an important role in influencing the final suitability of the device in practice. Therefore, in addition to the structural requirements for a stent to maintain a previously occluded vessel in a substantially open conformation, stents must also be biologically compatible, and must be chemically stable when exposed to a biological environment.
A variety of materials have been tested and used in stents to address the issues of biocompatibility and material stability. For example, polyurethanes have been used in long term implants, but are not always suitable for use in endovascular treatments, especially in small blood vessels. Small blood vessels are considered to be those with an inner diameter of 2.0 to 5.0 mm. In addition, many commercially available polymers are with additives, or have impurities, that are surface-active and so reduce their usefulness in some biological applications.
More recently, polymers have been developed which can be further modified by the covalent attachment of various surface-modifying end groups, these end groups reducing the reactivity of the material with cells and other factors that function in the immune response. End groups can also be useful in providing greater chemical stability to the material, reducing degradation and improving the longevity of the prosthesis. For example, U.S. Pat. No. 5,589,563 (Ward & White) discloses a series of biomedical base polymers with covalently attached end groups that give the polymer certain desirable properties. These modified polymers possess surface properties that improve the biocompatibility and overall performance of objects fashioned from them.
In addition to their biomechanical functionality, implantable medical devices like stents have been utilized for delivery of drugs or bioreagents for different biological applications. U.S. Pat. No. 5,891,108 (Leone et al.) discloses a hollow tubular wire stent with holes through which an active substance can be delivered to a site in a vessel. In some cases the drugs or bioreagents can be coated directly onto the surface of the implantable medical devices or mixed with polymeric materials that are then applied to the surface of the devices. For example, U.S. Pat. No. 5,599,352 (Dinh et al.) discloses a drug eluting stent comprising a stent body, a layer of a composite of a polymer combined with a therapeutic substance, overlaid by a second layer comprising fibrin.
However, each of these methods suffers from one or more problems including poor control of release or limitations of the form of drug or other reagent that can be applied. Also, these methods are unsuitable for situations where it would be desirable to maintain the bioactive molecule on the device rather than having it be released, in order to maintain a relatively high local activity of the reagent of interest.
As a result, in practice, the design and use of stents in the repair of aneurysms or other vessel defects or diseases typically represents a compromise among competing factors. First, the stent must adequately support the diseased or weakened region in order to prevent rupture of the aneurysm or vessel during and after stent placement, either of which could lead to serious complications including death, depending on the size, location and nature of the aneurysm or defect. Second, in the case of stents use in the repair of aneurysms, the stent must permit sufficient blood supply to maintain the patency of both the parent and perforator vessels, while at the same time limiting flow to the aneurysm proper. Generally speaking, flow of material through the framework of a stent is achieved by regulating the porosity of the stent.
Stent porosity can be managed in a number of ways. The simplest way is to manufacture the stent so that the framework itself defines the porosity of the device. However, in biological applications, regulating movement of materials on cellular or subcellular scale is required, and it is difficult and costly to manufacture stents that have such fine effective pore size. Other approaches have been to cover the stent framework for example with a membrane, where the membrane is either impermeable or porous as desired. U.S. Patent Application No. 2006/0217799 (Mailander et al.) discloses a stent comprising a grid or mesh structure in which one or more cells of the grid are covered with a membrane. Similarly, U.S. Patent Application No. 2006/0200230 (Richter) discloses a covering for an endoprosthetic device that comprises a sheath with holes of varying size and varying frequency disposed in different areas of the sheath.
However, a problem inherent with these designs is that they are not easily adapted for effecting vessel wall repairs where the area of disease, damage or weakness can vary in size. Thus, in order to optimally treat an aneurysm, it would be necessary to tailor the stent and its covering to more or less the precise size of the damaged area, in order to properly occlude the aneurysm site, while maintaining vessel patency in the parent vessel and any perforator vessels. Furthermore, these designs are not optimized such that they will generally provide flow to perforator vessels that are part of the collateral circulation in the area of the diseased, damaged, or weakened vessel, while blocking flow to an aneurysm.
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USPTO Backgrounds