Personalized prosthesis and methods of deployment

A personalized prosthesis for implantation at a treatment site of a patient includes a self-expanding mesh and/or membrane having collapsed and expanded configurations. The collapsed configuration is adapted to be delivered to the treatment site, and the expanded configuration is oversized relative to the treatment site and configured to engage the personalized prosthesis with the treatment site. The self-expanding mesh is configured to reduce in one or more dimensions in response to being constrained in the one or more dimensions, such that the mesh in the expanded configuration self-adjusts to the treatment site without buckling of the mesh. The self-expanding mesh or membrane forms a central lumen configured to allow blood or other body fluids to flow therethrough. Methods of manufacturing and delivery of the personalized prosthesis are also disclosed.

BACKGROUND OF THE INVENTION

1. Field of the Invention

The present application generally relates to medical prostheses, methods for fabricating the prostheses, and methods for treating diseased or damaged tissue. More specifically, the present application relates to treatment of blood vessels or other body lumens and body cavities, including aneurysms such as in the aorta or in the brain.

An aneurysm is the localized dilation of a blood vessel which presents a serious medical condition. Such distention is the result of localized weakening of the vessel often caused by atherosclerosis, infection, or congenital defects. Most commonly aneurysms occur in arteries at the base of the brain or in the aorta. Cases of significant distention risk the possibility of vessel rupture and the resulting internal hemorrhage is a life threatening medical emergency that requires immediate surgical intervention. Aneurysms that are large enough to present an unacceptable level of risk of rupture are treated with preemptive surgery.

The most reliable surgical remedy for aneurysms is excision of the aneurysm and repair of the afflicted blood vessel with a graft. However, this procedure requires highly invasive surgery and often requires clamping of a major vessel such as the aorta, which can place a large strain on the patient's heart. Patients requiring aneurysm treatment often have co-morbid risk factors such as diabetes, heart disease, and hypertension, and thus such patients can be poor candidates for such a stressful operation. Accordingly, newer endovascular grafting methods for minimally invasive intervention of aneurysms are favored over traditional grafts for some patients. These endovascular installed grafts or “endoluminal grafts” are installed by accessing the aneurysm through the femoral arteries and have stent-like scaffolding supports at its terminal ends. Endoluminal grafts, however, in some situations are more prone to post-operative complications than traditionally installed grafts. Within two years of installation, a significant number of aortic endoluminal grafts exhibit leakage at the proximal interface to the aorta, necessitating further endovascular surgical intervention. Additionally, a small portion of endoluminal grafts drift inside the repaired blood vessel and expose the aneurysm. Repair of a drifted graft requires open surgery in a patient who is likely a poor candidate for such a procedure.

Endoluminal grafting must overcome geometrical problems stemming from morphological variations in aneurysm presentation and location. While most aneurysms are “fusiform,” exhibiting distention along the entire circumference of the afflicted blood vessel, varied geometries exist. Some aneurysms display ballooning of the vessel on one side at a narrow neck (also referred to as saccular), or may have otherwise treacherous geometries. Other aneurysms may be located in close proximity to sensitive structures such as renal arteries. Endoluminal grafts in certain situations may encounter higher incidence of failure with non-fusiform geometries and may be unsuitable for implantation where the implants and their delivery techniques prove too incompatible or cumbersome for aneurysm geometry or location.

Since the introduction of the stent graft in 1992, there is a persistent problem of endoleaks. The purpose of the placement of the stent graft is to direct the blood flow through the lumen of the stent graft and isolate the aneurysm sac. Clinical success is determined by the complete exclusion of the sac. However, in more than 20% of the cases, the aneurysm sac is not effectively excluded whereby blood ‘leaks’ in to the sac. This leak is defined as ‘endoleak’. The result is the sac continues to grow due to the persistent pressure of the blood against a weakened blood vessel wall, the risk of the blood vessel wall rupture is not mitigated, and the treatment is deemed to be a failure. Endoleak is a major cause of complication, and the post-operative management of the endoleaks is cumbersome and messy.

There are actually five kinds of endoleaks associated with the currently marketed stent grafts. Type I endoleak refers to the leakage of the blood flow into the sac because of an incomplete seal at the ends of the stent graft. Type II endoleak occurs when blood flows into the sac from the side branches in a retrograde fashion. Type III endoleak is defined when there is an ineffective seal at the joints of two limbs of the stent graft. Type IV endoleak happens in there is a defect, such as porosity in the graft material. Finally, Type V endoleak, known as endotension, is not really a leak, but a persistence of blood pressure in the aneurysm sac which continues to enlarge the sac towards eventual rupture if left untreated.

The most persistent endoleak is Type II where the blood comes into the aneurysm pocket from the side branches. The current therapy is to block the side branches from having any flow outward or inward. Preferred embodiments of the current invention may provide a more effective method of achieving the same.

Given these concerns, there is strong unmet need for improved endoluminal grafts and delivery methods. Such an improved design preferably facilitates more reliable repair of aneurysms over a wider space of geometries and the ability to be delivered with such finesse as to shorten procedure time and expand the number of aneurysms that are treatable endovascularly. It would also be desirable if such improved endoluminal grafts also fit the patient's anatomy more accurately and therefore help prevent endoleaks and more securely anchor the endograft in the aneurysm and prevent drifting. At least some of these objectives will be met by the devices described herein.

2. Description of Background Art

SUMMARY OF THE INVENTION

The present application generally relates to medical prostheses, structures of the prosthesis and the delivery system, and methods for deploying the prosthesis at the intended site in the body. More specifically, the present application relates to treatment of blood vessels or other body lumens and body cavities, including aneurysms such as in the aorta, other arteries, or arteries in the brain. The techniques disclosed herein generally result in a personalized prosthesis that is designed and manufactured to match the anatomy of the patient's diseased or damaged tissue. The personalized prostheses may be commercially distributed once appropriate regulatory approvals have been obtained (e.g. Food and Drug Administration), and are not necessarily the same as “custom devices” defined in 21 CFR § 812.3(b), which applies to non-commercial distribution of medical devices under certain circumstances, such as compassionate use.

The prostheses disclosed herein, such as mesh alone, membrane covered mesh, or membrane alone may be implanted into a treatment site such as an aneurysm to stabilize the aneurysm and to help prevent it from growing larger. This applies to incipient aneurysms (e.g. untreated early stage aneurysms usually less than 50 mm in diameter) or larger, later stage aneurysms may also be treated using the prostheses described herein.

In one aspect, disclosed herein is a system for treating tissue at a treatment site in a bodily lumen. The system comprises a self-expanding prosthesis having a collapsed configuration and an expanded configuration in which an outer surface of the prosthesis is sized and shaped to match contours of an inner wall of the treatment site. The system further comprises a retractable sheath disposed over and constraining the self-expanding prosthesis in the collapsed configuration. The self-expanding prosthesis and retractable sheath are positioned at the treatment site, and progressive retraction of the sheath allows the prosthesis to progressively self-expand to the expanded configuration from a first end portion of the prosthesis to a second end portion of the prosthesis opposite the first end portion. The prosthesis is further configured to self-orient as the prosthesis is moved axially toward the treatment site so that contours of the outer surface of the prosthesis rotationally align with the contours of the inner wall of the treatment site. The bodily lumen may comprise a blood vessel and the treatment site may comprise an aneurysm in the blood vessel.

The prosthesis may be configured to self-expand or self-orient when the prosthesis is disposed in the treatment site. The prosthesis may be configured to self-expand or self-orient when a portion of the prosthesis extends beyond the treatment site.

The prosthesis may progressively self-expand in the treatment site as the prosthesis is moved toward the treatment site. The prosthesis may progressively self-expand such that the first end portion is fully expanded while the second end portion remains constrained by the sheath.

The system may further comprise one or more actuation elements coupled to a proximal portion or a distal portion of the prosthesis, wherein the one or more actuation elements are configured to push or pull the prosthesis. The one or more actuation elements may comprise one or more wires coupled to the proximal or the distal portion of the prosthesis.

The system may further comprise an expandable member disposed under the prosthesis, the expandable member configured for tacking the prosthesis into the treatment site. The expandable member may comprise an expandable wire basket or a balloon.

The prosthesis may comprise an inner surface and an outer surface, and the inner surface may be substantially smooth, and while the outer surface may be textured. The prosthesis may be formed with one or more filaments twisted with one another to form a directional pattern in the prosthesis.

The prosthesis may be disposed in a twisted configuration in the retractable sheath. The prosthesis may be biased to twist in a pre-determined direction upon self-orientation. The prosthesis may self-orient with sufficient force to overcome static friction between the prosthesis engaged with tissue in the treatment region.

The system may further comprise one or more lateral apertures in the prosthesis, the one or more lateral apertures sized to match one or more ostia along the treatment region. The one or more lateral apertures may align with the one or more ostia after self-orienting of the prosthesis. A location of the one or more lateral apertures may be based on one or more images of the treatment region.

In another aspect, disclosed herein is a method for deploying a prosthesis personalized for a patient in a bodily lumen of the patient. The method comprises advancing the prosthesis in a collapsed configuration through the bodily lumen toward a target region in the bodily lumen. The method further comprises allowing the prosthesis to progressively self-expand from the collapsed configuration to an expanded configuration in which an outer surface of the prosthesis is sized and shaped to match contours of an inner wall of the target region. The method further comprises self-orienting the prosthesis such that contours of the outer surface of the prosthesis rotationally align with the contours of the inner wall.

Advancing the prosthesis may comprise advancing the prosthesis so that a portion of the prosthesis extends beyond the target region. Allowing the prosthesis to progressively self-expand may comprise removing a sheath from the prosthesis. Allowing the prosthesis to progressively self-expand may comprise self-expanding from a far end portion to a near end portion of the prosthesis. The far end portion may be further from an operator of prosthesis than the near end portion.

Self-orienting may comprise moving the prosthesis toward the target region. Moving the prosthesis toward the target region may concurrently remove a constraint from the prosthesis, the constraint provided by the target region. Self-orienting may comprise self-rotating of the prosthesis about a longitudinal axis of the bodily lumen and rotationally aligning contours of the outer surface of the prosthesis with the contours of the target region.

Self-orienting may comprise urging the prosthesis to self-orient with the target region due to mismatching between contours of the expanded outer surface of the prosthesis and contours of the inner wall in contact with the expanded outer surface. Release of potential energy from the mismatching into a lower energy state may urge the prosthesis to self-orient and conform with the target region.

The bodily lumen may comprise a blood vessel and the target region may comprise an aneurysm in the blood vessel. A far end portion of the prosthesis may be closer to a heart of the patient than a near end portion of the prosthesis.

The method may further comprise translating or rotating the prosthesis to facilitate the self-orientation of the prosthesis. The translating may comprise pulling a far end or a near end of the prosthesis. Translating or rotating the prosthesis may overcome static friction between a surface of the prosthesis and a surface of the target.

The prosthesis may further comprise a polymeric coating covering the self-expanding wire mesh. The prosthesis may have a central lumen for fluid flow therethrough.

Self-orienting may comprise aligning one or more ostia in the bodily lumen of the target region with one or more lateral apertures in the prosthesis that are sized to match the one or more ostia. A location of the one or more lateral apertures may be based on one or more images of the target region.

The method may further comprise visualizing the prosthesis as the prosthesis is advanced or allowed to progressively self-expand. The method may further comprise tacking the prosthesis into the target with an expandable member. The method may further comprise loading the prosthesis onto a delivery catheter, wherein the prosthesis is loaded in a twisted configuration onto the delivery catheter.

In another aspect, a personalized prosthesis for implantation at a treatment site comprises a self-expanding mesh having a collapsed configuration and an expanded configuration, wherein the collapsed configuration is adapted to be delivered to the treatment site, and wherein the expanded configuration is adapted to expand the personalized prosthesis into engagement with the treatment site. The mesh in the expanded configuration may be personalized to match the treatment site, the mesh having an outer surface that substantially matches the treatment site shape. The self-expanding mesh may form a central lumen configured to allow blood or other body fluids to pass therethrough. The mesh may be configured to be reduced in size in one or more dimensions in response to being constrained in the one or more dimensions.

The mesh may be formed from a plurality of twisted wires, the twisted wires having a pattern comprising a first twist with a first number of loops and an adjacent second twist with a second number of loops, the second number of loops different from the first number of loops. The first twist can allow movement of wires in the loop relative to one another and the second twist can constrain movement of wires in the loop relative to one another. Thereby, the mesh in the expanded configuration can self-adjust to conform to the treatment site without buckling of the mesh. The first twist may comprise two loops and the second twist may comprise three loops, wherein the wires in the first twist move relative to one another to at least partially open one or more of the two loops in response to the mesh in the expanded configuration being constrained within the treatment site.

The pattern of the twisted wires may comprise repeating sub-patterns each comprising three of the first twists adjacent to one of the second twists. The pattern of the twisted wires may comprise repeating sub-patterns each comprising two of the first twists adjacent to one of the second twists.

The self-expanding mesh may comprise one or more filaments woven together to form a first overlapping region and a second overlapping region. In the first overlapping region the filaments may overlap with one another a first number of times, and in the second overlapping region the filaments may overlap with one another a second number of times different than the first number of times. The self-expanding mesh may comprise barbs or hooks adapted to engage tissue at the treatment site and anchor the personalized prosthesis to the treatment site. The self-expanding mesh may comprise a plurality of overlapping filaments forming overlapping regions, wherein the overlapping regions may form raised surfaces adapted to engage tissue at the treatment site and anchor the prosthesis.

The personalized prosthesis may further comprise a membrane coupled to the mesh, wherein the membrane is elastic and conforms to the self-expanding mesh. The membrane may have an outer surface that substantially matches the treatment site shape in the expanded configuration, and the membrane may form the central lumen. The membrane may comprise a resilient polymer impermeable to blood. The membrane may comprise an elongated neck portion, wherein invagination of the elongated neck into the personalized prosthesis forms the central lumen.

The personalized prosthesis may further comprise one or more radiopaque markers coupled to the membrane or the self-expanding mesh for facilitating implantation of the prosthesis at the treatment site.

The personalized prosthesis may further comprise one or more apertures extending through a sidewall of the prosthesis. The one or more apertures may be fluidly coupled with the central lumen to allow blood flow or other fluids to flow between the central lumen and the one or more apertures. The one or more apertures may be configured to accommodate side branch vessels or other body passages such that the prosthesis does not obstruct blood flow or fluid flow therethrough. A location of the one or more apertures may be based on one or more images of the treatment site.

The lumen may not substantially alter blood flow path across the treatment site. The lumen may have a cylindrical shape. The cylindrically shaped lumen may be formed from an invaginated portion of the personalized prosthesis. The outer surface of the self-expanding mesh may be textured and while an inner surface of the self-expanding mesh forming the central lumen may be smooth. The personalized prosthesis may further comprise a smooth lining disposed over an inner surface of the self-expanding mesh.

The self-expanding mesh in the expanded configuration may be oversized relative to a size of the aneurysm. The self-expanding mesh in the expanded configuration may be undersized relative to a size of the aneurysm. The self-expanding mesh in the expanded configuration may be sized to match a size of the aneurysm.

In another aspect, a personalized prosthesis for treating an aneurysm having a lumen extending therethrough comprises a wire mesh having a collapsed configuration and an expanded configuration, wherein the collapsed configuration is adapted to be delivered percutaneously to the aneurysm, and wherein the expanded configuration is configured to conform with the lumen. The wire mesh may be formed from a plurality of twisted wires, the twisted wires having a pattern comprising a first twist with a first number of loops and an adjacent second twist with a second number of loops, the second number of loops different than the first number of loops. The first twist may allow movement of wires in the loop relative to one another and the second twist may constrain movement of wires in the loop relative to one another, thereby allowing the self-adjustment of the oversized wire mesh to conform to the lumen without buckling of the wire mesh.

In another aspect, a method for treating tissue at a treatment site comprises providing an implantable prosthesis having a central lumen, an expanded configuration and a collapsed configuration. The implantable prosthesis may be biased to expand into the expanded configuration, and the implantable prosthesis may be personalized to match a shape of the treatment site. The central lumen may be configured to allow blood flow or other body fluids to pass therethrough. The method further comprises advancing the implantable prosthesis in the collapsed configuration to the treatment site. The method further comprises self-expanding the implantable prosthesis into the expanded configuration, wherein in the expanded configuration the implantable prosthesis has a shape that substantially matches the shape of the treatment site such that the implantable prosthesis expands substantially into engagement with tissue at the treatment site. The method further comprises self-adjusting one or more dimensions of the implantable prosthesis in the expanded configuration such that a size of the expanded implantable prosthesis matches a size of the treatment site. The method further comprises reinforcing the tissue with the implantable prosthesis.

The implantable prosthesis may comprise a wire mesh, and self-adjusting one or more dimensions of the implantable prosthesis may comprise constraining at least some wires in the wire mesh from moving away from one another in a first twisted region and allowing at least some wires in the wire mesh to move away from one another in a second twisted region different than the first twisted region, thereby self-adjusting the wire mesh to the treatment site.

The implantable prosthesis may comprise a self-expanding wire mesh surrounded by a resilient polymer cover. The lumen may have a cylindrical shape. The lumen may be formed from an invaginated portion of the implantable prosthesis. The cylindrically shaped lumen may be disposed inside the implantable prosthesis. The lumen may not substantially alter blood flow path across the treatment site.

Advancing the implantable prosthesis may comprise advancing the implantable prosthesis through a blood vessel. Radially expanding the implantable prosthesis may comprise retracting a sheath away from the implantable prosthesis, thereby allowing the implantable prosthesis to self-expand into the expanded configuration. Reinforcing the tissue may comprise anchoring the implantable prosthesis to the tissue.

The treatment site may comprise an aneurysm, and reinforcing the tissue may comprise preventing the aneurysm from enlarging. The treatment site may comprise an aneurysm and reinforcing the tissue may comprise excluding the aneurysm. Reinforcing the tissue may comprise anchoring the implantable prosthesis with the tissue. The anchoring the implantable prosthesis may comprise engaging barbs on the implantable prosthesis with the tissue. Reinforcing may comprise constraining the tissue from moving radially outward or radially inward.

The implantable prosthesis may comprise one or more radiopaque markers, and the method may further comprise aligning the one or more radiopaque markers with one or more anatomical features at the treatment site.

The implantable prosthesis may comprise one or more apertures in a sidewall thereof, and the method may further comprise aligning the one or more apertures with one or more ostia of side branch vessels or body passages at the treatment site, thereby preventing obstruction of the one or more side branch vessels or the body passages. A location of the one or more apertures may be based on one or more images of the treatment site.

The method may further comprise sealing the implantable prosthesis against the tissue at the treatment site to prevent blood flow therepast. The method may further comprise obstructing fluid flow through a side branch vessel in the treatment site by apposing the implantable prosthesis against an ostium of the side branch vessel.

The implantable prosthesis may be oversized or undersized relative to a size of the treatment site. The implantable prosthesis may be sized to match a size of the treatment site.

In another aspect, disclosed herein is a method for manufacturing a personalized implantable prosthesis in a manufacturing facility. The method comprises providing one or more images of a treatment site in a patient, creating a digital data set characterizing shape and volume of the treatment site based on the one or more images, and transforming the digital data set into machining instructions. The method further comprises forming a mandrel using the machining instructions, wherein the mandrel has a shape that substantially matches the treatment site shape. The method further comprises applying a mesh to the mandrel, the mesh configured to be reduced in size in one or more dimensions in response to being constrained in the one or more dimensions. The method further comprises heat treating the mesh while the mesh is disposed over the mandrel so that the mesh is biased to return to a shape substantially matching the shape of the treatment site. Thereby the personalized implantable prosthesis is formed, the personalized implantable prosthesis having a collapsed configuration and an expanded configuration. The personalized implantable prosthesis may be adapted to be delivered to the treatment site in the collapsed configuration, and the personalized implantable prosthesis may be biased to return to the expanded configuration having the shape substantially matching the treatment site shape.

The mesh may comprise a first twisted region of wires that are adapted to move relative to one another and a second twisted region of wires that are unable to move relative to one another, such that movement of the wires in the first twisted region of wires allow the reduction in size in the one or more dimensions of the mesh. The personalized implantable prosthesis may be oversized or undersized relative to the treatment site. The personalized implantable prosthesis may be exactly sized to match the treatment site. A diameter of the mandrel may be oversized relative to the treatment site by about 2% to about 40% of a corresponding diameter of the treatment site. The diameter of the mandrel is oversized relative to the treatment site by about 5% to about 15% of a corresponding diameter of the treatment site.

Providing the one or more images may comprise providing one or more computerized tomography (CT) images, one or more magnetic resonance images (MRI), one or more x-ray images, one or more ultrasound images, or one or more an angiography images of the treatment site. Transforming the digital data set into machining instructions may comprise transferring the digital data set into a CAD/CAM system. Forming the mandrel may comprise machining a piece of stock or 3-D printing the mandrel.

Applying the mesh to the mandrel may comprise slidably disposing the mesh over the mandrel. Applying the mesh to the mandrel may comprise wrapping a filament around the mesh and the mandrel. Applying the mesh to the mandrel may comprise wrapping a preformed flat mesh therearound.

The method may further comprise forming at least one side aperture in the personalized implantable prosthesis, the at least one side aperture configured to be aligned with a side branch vessel in the treatment site. Forming the at least one side aperture may comprise locating the at least one side aperture based on the digital data set created from the one or more images.

The method may further comprise forming a membrane coupled to the mesh. Forming the membrane may comprise attaching a polymer cover to the mesh. Forming the membrane may comprise dip coating a polymer cover onto the mesh.

The method may further comprise mounting the implantable prosthesis onto a delivery catheter, cleaning the prosthesis and delivery catheter, packaging the implantable prosthesis, and terminally sterilizing the implantable prosthesis.

The method may further comprise requesting verification that the shape of the personalized implantable prosthesis is appropriate for implantation at the treatment site before shipping the personalized implantable prosthesis from the manufacturing facility. The verification may be performed by a physician. The verification may be performed over the Internet or via the cloud. The method may further comprise shipping the personalized implantable prosthesis to a hospital.

The method may further comprise mounting the personalized implantable prosthesis on a delivery catheter, placing the personalized implantable prosthesis and the delivery catheter in packaging, sterilizing the personalized implantable prosthesis and the delivery catheter in the packaging, and requesting verification that the personalized implantable prosthesis is appropriate for implantation at the treatment site before opening the sterile packaging. The verification may be performed by a physician. The verification may be performed over the Internet or via the cloud.

The method may further comprise removing the implantable prosthesis from the mandrel so that a central lumen extends through the implantable prosthesis. The treatment site may be an aneurysm.

In another aspect, disclosed herein is a method for manufacturing a personalized prosthesis for treating an aneurysm. The method comprises forming a mandrel matching a shape of the aneurysm, and disposing a wire mesh over the mandrel. The wire mesh has a first twisted region of wires that are adapted to be movable relative to one another and a second twisted region of wires that are unable to move relative to one another. The method further comprises setting a shape of the wire mesh.

The mandrel may be oversized or undersized relative to the shape of the aneurysm. The mandrel may be sized to match the shape of the aneurysm. The mandrel may be 2%-40% oversized relative to the aneurysm. The mandrel may be 5%-15% oversized relative to the aneurysm. The mandrel may have a size that matches the aneurysm.

These and other aspects and advantages of the invention are evident in the description which follows and in the accompanying drawings.

INCORPORATION BY REFERENCE

DETAILED DESCRIPTION OF THE INVENTION

Specific embodiments of the disclosed device, delivery system, and method will now be described with reference to the drawings. Nothing in this detailed description is intended to imply that any particular component, feature, or step is essential to the invention.

The present invention will be described in relation to an abdominal aortic aneurysm. However, one of skill in the art will appreciate that this is not intended to be limiting, and the devices and methods disclosed herein may be used in aneurysms in other parts of the body such as in the brain, as well as used to treat other hollow anatomical structures including ducts, vessels, organs, or any other part of the body where there is a need to reinforce a lumen, channel or other body space. For example, a personalized prosthesis may be fabricated using the techniques described herein for implantation in or around the bladder in order to treat incontinence, or the prosthesis may be personalized to treat a diseased or damaged pyloric valve in the stomach, or other body passages such as a biliary duct.

TERMINOLOGY

In this description the terms ‘distal’ and ‘proximal’ are used to denote the location of a certain aspect in the structure of the prosthesis or the delivery catheter system. In the parlance commonly used in catheter art, the term ‘proximal’ refers to a location closer to the user (e.g. the physician). Conversely, the term ‘distal’ is used to describe locations which are farther away from the user. For example, the tip of the catheter would be ‘distal’ to the handle of the catheter. Generally, the parts of the catheter outside the body during use are proximal to the parts which are inside the body. Incidentally, this terminology of ‘distal’ and ‘proximal’ is also used in anatomical reference to describe various locations of the body. Here, ‘proximal’ refers to the locations closer to the heart, and ‘distal’ refers to the locations farther away from the heart. Thus, for example, the knee is distal to the abdomen of the patient.

These two notions of the same terms can be at conflict at times and prone to creating confusion. For this disclosure, we will use the terms ‘distal’ and ‘proximal’ from the point of view of the user and not in the anatomical sense. The anatomical aspects, as they pertain to the treatment of the aortic aneurysms, will use the terms ‘superior’ and ‘inferior’ or equivalents which have standard meaning in the art.

In addition, the following abbreviations are used in this specification:

SB—Side branch blood vessel originating at the site of the AAA

FIG. 1Aillustrates typical anatomy in a normal section of the abdominal aorta A where blood flows downstream as indicated by the arrow from the heart toward the legs. The aorta is typically a gradually tapering cylinder. A pair of renal arteries R branch off laterally from the aorta A and provide blood to the kidneys (not shown). The aorta bifurcates into two common iliac arteries I which then further bifurcate into the external iliac artery EI and the internal iliac artery II. After the external iliac arteries EI pass the inguinal ligament (not shown) they are then generally referred to as the femoral arteries F. Thus, the aorta provides for smooth blood flow from the heart to the lower extremities of the body.

However, in some cases, the tissue in the aorta may become weakened due to disease or damage thereby resulting in a bulged region known as an aneurysm. The aneurysm may be at any point along the abdominal aorta. For example,FIG. 1Billustrates a suprarenal aortic aneurysm where the aneurysm AA is superior to (or upstream or above) the renal arteries R.FIG. 1Cillustrates an infrarenal aneurysm AA which is inferior to (or downstream or just below) the renal arteries and this type of aneurysm represents the majority of abdominal aortic aneurysms.FIG. 1Calso illustrates that the aneurysm does not always remain strictly in the aorta, and that the aneurysm may extend into the iliac arteries and femoral arteries.FIG. 1Dillustrates a juxtarenal aortic aneurysm AA where the aneurysm extends over the portion of the aorta from which the renal arteries branch off. Each of the aneurysms illustrated inFIGS. 1B-1Dare referred to as fusiform aneurysms in which the weakened aorta and resulting bulge extend essentially all the way around the vessel. However, aneurysms may also be saccular in which only a portion of the vessel wall bulges outward, such as inFIG. 1E.FIG. 1Fillustrates the typical anatomy of the abdominal aortic aneurysm (AAA). The blood flows downstream as indicated by the arrow15from the heart toward the legs. A pair of renal arteries RA branch off laterally from the aorta A and provide blood to the kidneys K. The AAA may also have one or more side branches SB which supply blood to the neighboring tissues.

FIG. 1Gshows an AAA, or a typical fusiform aneurysm of the infrarenal abdominal aorta, with a mural thrombus. The heart supplies blood to the abdomen and lower parts of the body through the lumen2000. The aortic aneurysm AAA is essentially a bulge in the otherwise cylindrical tubular blood vessel. This bulge is created as the wall of the blood vessel weakens over time and the pressure of the blood pushes the wall outward. The blood flow2002typically becomes turbulent giving rise to the formation of mural thrombus2004.

FIG. 1Hshows the cross section of the aorta through WW ofFIG. 1G. Vessel wall2006contains the mural thrombus2004leaving a narrowed lumen2000for the blood to flow therethrough. Typically, a patient goes through a CT scan and the aortic aneurysm AAA is diagnosed. The CT scan shows the blood volume of the lumen, and it does not show the blood vessel wall or the outer surface of the aorta.

Standard surgical procedures for aneurysm repair often use a natural graft or an artificial graft typically made of Dacron™ polyester or expanded polytetrafluorinated ethylene (ePTFE) to replace the damaged or diseased section of the vessel. This procedure is highly invasive, can result in a number of post-operative complications, and requires a lengthy recovery period.

More recently, minimally invasive endovascular repair techniques have been developed in which a stent-graft is delivered to the treatment site.FIG. 2shows a stent graft5inserted into the AAA site in a minimally invasive procedure EVAR (endovascular aneurysm repair). The stent-graft, which is substantially cylindrical in shape, is then radially expanded into the aneurysm thereby forming a new lumen for blood flow that excludes the aneurysm. While stent-grafts are promising, the implanted device may obstruct blood flow to side branch vessels SB, or the implant may be pushed downstream away from the treatment site due to the force of the blood and its pulsating nature. This is sometimes referred to as “windsocking.”

Additionally, stent-grafts do not always seal perfectly against the vessel wall, thereby allowing blood to continue to pressurize the aneurysm sac28. Endoleaks are a major cause of failure in the treatment of aneurysms with stent-grafts. Endoleaks have been classified into several categories shown inFIG. 2as I, II, III, and IV. In Type I endoleaks, blood flows into the aneurysm sac due to incomplete sealing at the proximal end of the stent-graft. The proximal end as used herein with respect to the prosthesis is the end closest to the heart, and the distal end of the prosthesis is the downstream end. When referring to a delivery system used to deliver a prosthesis, the proximal end of the delivery system is the end that is furthest away from the heart and usually closest to the operator, and the distal end is the closest to the heart and typically furthest away from the operator. Type II endoleaks result when blood flows into the aneurysm sac from collateral vessels, such as side branch vessels SB. Type III endoleaks result in blood flow into the aneurysm sac due to poor sealing between stent-graft joints or rupture of the stent-graft. Type IV endoleaks result in blood flow into the aneurysm sac due to excessive or unwanted porosity in the stent-graft that permits blood to flow through the stent-graft into the aneurysm. Endoleaks may result from improper fitting or matching of the stent-graft to the patient's anatomy.

Thus it is clear that there is a need for a prosthesis that can be used to treat aneurysms that has more conformal anchoring to prevent windsocking, and that fits the aneurysm anatomy more accurately in order to minimize the possibility of endoleaks. In some cases, it may be advantageous for the prosthesis to maintain blood flow to side branch vessels. A personalized prosthesis as disclosed herein will address at least some of these issues. Current imaging systems can be linked with computer aided design (CAD) and computer aided manufacturing (CAM) systems to allow a prosthesis to be fabricated that matches the patient's anatomy. Such a personalized prosthesis may also be used to treat normal or presymptomatic tissue of a patient at risk of developing an aneurysm or at early stages of development of an aneurysm.

FIG. 3Aillustrates an exemplary embodiment of a personalized stent graft (“PSG”) or prosthesis10. The PSG10is shaped to conformally fit inside the AAA of a specific patient. The PSG10comprises a plurality of intertwined wire filaments, of material such as nitinol, twisted together in a ‘chicken wire’ format (also known as gabion basket fence) to form cells12which in aggregate form the wire frame structure14. The wire frame14can be made from the filaments of any suitable material known in the art for construction of the stent grafts. The wire frame14can be configured to substantially match or conform to the internal geometry of the target vessel of the patient, using methods as described herein. In this disclosure, the terms filament and wire are used interchangeably. A portion of the PSG may be covered with a membrane16(shown as a shaded area inFIG. 3A), which may comprise a biocompatible material such as Teflon, Dacron, or silicone.

The PSG10may comprise one or more lateral openings or apertures, known as fenestrations in the art, such as openings18and20at its superior end. These openings can correspond to the ostia of the renal arteries RA of the patient. The location and construction of these fenestrations18and20may be determined by the anatomical image, such as a CT scan, of the AAA. These fenestrations can allow unimpeded blood flow into the renal arteries RA when the PSG is implanted. Finally, the portion22of the PSG10superior to the fenestrations18and20may optionally be uncovered by the membrane material16. The PSG10may further comprise one or more radio-markers25which can present as opaque images during x-ray fluoro imaging, marking the superior end of the said PSG10. This feature may be used in guiding the deployment of the PSG in the AAA.

FIG. 3Bshows the PSG10deployed in the AAA. The PSG can be positioned in the AAA in a conformal manner such that there is minimum or no space between the outer surface24of the PSG10and the inner surface26of the blood vessel wall29forming the AAA. The side branches SB can thus be blocked, and the aneurysm sac or pocket28as shown inFIG. 2between the stent graft and the blood vessel wall can be eliminated, thereby preventing endoleaks.

The features and elements of a personalized prosthesis or PSG, and methods of manufacture and use thereof, are described in further detail herein.

Referring again toFIG. 2, conventional stent grafts have a requirement (known as ‘indication’ in FDA parlance) that there be a neck length NL available in the patient for him/her to be suitable for the EVAR treatment. The neck length NL is a region inferior to the renal arteries RA between the RA and the beginning of the bulge of the AAA. Typically, the neck length needs to be 10 mm or more for the EVAR procedure. Additionally, patients with angulated AAA (where neck length portion NL is curved), juxtarenal AAA (where the AAA involves the renal arteries, as inFIG. 1D) and suprarenal AAA (as inFIG. 1B) are excluded from the EVAR treatment mainly due to the inability to seal around the stent graft to prevent Type I endoleaks.

In the case of the PSG, all the described restrictions of the conventional stent graft can be substantially eliminated as the PSG can be fabricated to match the anatomy of the aneurysms anywhere in the aortic and/or iliac vessels. The resulting PSG can be implanted in the patient at any aneurysm location to provide a more effective treatment. A PSG or personalized prosthesis as disclosed herein can thus allow many more patients to be treated than with a conventional stent graft.

FIG. 4is a flow chart which illustrates an exemplary method of fabricating a personalized prosthesis that can be used to treat aneurysms or any other treatment region. The method includes obtaining one or more images202of the treatment region which in this case is an aneurysm. These images may be obtained using computerized tomography (CT), x-ray, angiography, magnetic resonance imaging (MRI), ultrasound, or other imaging techniques known to those of skill in the art. The images may be stored on any storage media such as a CD-ROM, flash memory stick, etc., or the images may be stored in the cloud, on a remote server, or any other convenient and secure location. The images may be transferred to any of these locations using the Internet. Once the images are stored, the images or the digital data representing the images may be input204into a computer aided design/computer aided manufacturing (CAD/CAM) system. The CAD/CAM system then converts the images into a digital data set that can then be translated into machining instructions which are provided to a machining device such as a CNC lathe (e.g., four-axis CNC machine), mill, electrical discharge machine (EDM), etc. and the machining instructions are used by the machining device to machine206or otherwise form a mandrel or a mold having a shape that substantially matches the shape and volume of the treatment region. Thus the contours of the mandrel will match the contours of the treatment region, and the mandrel will substantially fill the volume of the treatment region, typically a body cavity, lumen, or other passage. The CAD/CAM system may be programmed to compensate for the thickness of materials that are applied to the mandrel later on, thus the mandrel may be slightly smaller than the actual size of the treatment region. In other embodiments, the mandrel shape will match the contours of the treatment region without compensating for material thickness. In both cases, the resulting mandrel shape substantially matches the treatment region shape and size, and the mandrel will substantially fill the volume of the treatment region. For example, in the case of an abdominal aortic aneurysm, the mandrel will substantially fill the volume of the aneurismal sac as well as a portion of the aneurysm neck and legs. In other embodiments, the mandrel shape may be oversized relative to the actual size of the treatment region in order to allow the prosthesis manufactured from the mandrel to self-adjust in size to match the treatment region, as described in further detail herein.

Once the mandrel is formed, it can be used as a master mold from which a personal prosthesis is fabricated. The personal prosthesis will then have a size and shape that substantially matches the treatment region which allows the personal prosthesis to anchor itself at the treatment region and prevent endoleaks and windsocking. A wire mesh is either pre-made208or otherwise provided. The mesh is preferably tubular and cylindrically shaped with both ends open so that the mesh may be slidably disposed over the mandrel like a sock, or in other embodiments the wire mesh may be wound210on the mandrel. The mesh and mandrel are then placed in a furnace, oven, salt bath, etc. to an elevated temperature for a desired time. The mesh and mandrel are then removed and cooled using a prescribed cooling procedure such as air cooling, quenching in oil or water, etc. This heat treats212the wire mesh and the wire mesh takes a set to the shape of the mandrel. Heat treating of metals, in particular self-expanding metals is known in the art. The formed mesh is then removed from the mandrel. In this embodiment, or any of the embodiments disclosed herein the wire mesh is preferably self-expanding, and may be made from metals such as superelastic nitinol, and thus the mesh will have an expanded configuration which matches the mandrel and hence also substantially matches the shape of the treatment region. When tension is applied to the ends of the mesh, the mesh will collapse into a collapsed configuration which has a lower profile and is suitable for loading onto a delivery catheter for endovascular delivery to the treatment region. The wire mesh in this or any of the embodiments described herein may also be a shape memory alloy such as nitinol such that placement of the mesh in a patient's body heats the mesh above a transition temperature and causes the mesh to radially expand outward. In still other embodiments, the mesh may be balloon expandable, so it may be delivered over an expandable member such as a balloon. When the balloon is expanded, the mesh similarly expands with the balloon.

Once the wire mesh has been heat treated, a fabric or polymer coating may be applied214to the wire mesh to form a membrane over the wire mesh. The coating may be Dacron® polyester, expanded polytetrafluorinated ethylene (ePTFE), silicone, polyurethane, or other materials known in the art. The coating may be a sheet or tube of the material coupled to the mesh with adhesives, sutures, encapsulation, etc., or the mesh may be dip coated in order to apply the polymer to the mesh. The coating is preferably biocompatible and impermeable to blood or other body fluids. It may also be biodegradable and be made of materials such as polylactic acid (PLA) or polyglycolic acid (PGA). The resulting wire mesh with polymer coating or membrane forms a personalized implantable prosthesis having a shape that matches the treatment region and substantially fills the volume of the treatment region, in this case, the aneurismal sac. In other embodiments, the wire mesh remains uncoated and uncovered and forms the personalized prosthesis. The personalized implantable prosthesis is then coupled to a delivery system215such as a delivery catheter, and the system is then cleaned, packaged, and terminally sterilized216using manufacturing processes known to those of skill in the art. For example, packaging may comprise placing the prosthesis in a procedure tray and sealing the tray with a Tyvek® lid, and terminally sterilizing the prosthesis may comprise gassing the prosthesis with ethylene oxide, autoclaving it with steam, or irradiating it with gamma or electron beam irradiation. In alternative embodiments, the coating may be applied directly to the mandrel without the mesh, thereby forming the prosthesis.

In some embodiments, the physician optionally may then confirm218that the resulting personal prosthesis is indeed the correct one for a particular patient prior to shipping the prosthesis from the factory. The verification may be conducted visually over the Internet or via the cloud by verifying size, shape, or dimensions of the prosthesis. Once the verification is complete, the personal prosthesis may be shipped219from the manufacturing facility to the doctor at a hospital, surgicenter, clinic or other place of business. Once received, the doctor may then optionally re-verify220that the prosthesis is the correct size and shape for the patient prior to opening up the sterile package. If the prosthesis is incorrect, it may be returned to the manufacturing facility. Verification may be accomplished by scanning a bar code and/or using the Internet or via connection to cloud servers. Once verification is complete, the personal prosthesis may be implanted222in the appropriate patient. One of skill in the art will also appreciate that appropriate patient privacy must be maintained during the entire personalized manufacturing process as required by the Health Insurance Portability and Accountability Act (HIPAA). In an alternative embodiment, the mesh alone may be formed over the mandrel and then delivered as described herein to treat the diseased or damaged tissue. Similarly, in another alternative embodiment, a resilient polymer may be formed directly over the personalized mandrel without the mesh. This may then be used to treat the diseased or damaged tissue as described herein.

FIGS. 5A-5Iillustrate exemplary methods of fabricating a personalized prosthesis or PSG for treatment of an aneurysm.FIG. 5Aillustrates an infrarenal aneurysm AA similar to that illustrated inFIG. 1Cabove. Using the fabrication technique described above, images of the aneurysm may be obtained using CT scans, or any of the other techniques described herein or known in the art. The image is then used to create a mandrel302having a surface304which substantially matches the contours of the inner wall of the aneurysm, as shown inFIG. 5B. For example, the mandrel may be machined from a piece of stock, or it may be 3-D printed or molded. The mandrel may be made slightly undersized in order to accommodate for material thicknesses that are disposed on top of the mandrel, or the mandrel may be made oversized to provide a slightly oversized prosthesis. Alternatively, as described in further detail herein, the mandrel may be made oversized to produce a slightly oversized prosthesis that can self-adjust its shape and dimensions when deployed within an aneurysm. The mandrel may be made from a metal such as stainless steel or aluminum, or any other material that resists the heat experienced during heat treatment, such as a suitable ceramic material or polymeric material. Once the mandrel is made, a wire mesh306may be disposed over the mandrel302such that the mesh takes the shape of the mandrel and hence the mesh then also has a shape which substantially matches the shape of the aneurysm. In some embodiments, the wire mesh306may be pre-fabricated into a tubular sock-like shape that can be easily placed over the mandrel as seen inFIG. 5C. Alternatively, the wire mesh may be wound and formed over the mandrel. In some embodiments, as seen inFIGS. 5D-5F, a flat preformed mesh306a(best seen inFIG. 5D) may be wrapped around the mandrel302as seen inFIG. 5E. Once wrapped, the ends of the flat mesh may be affixed to one another using methods known in the art such as welding, suturing, tying, bonding, soldering, etc. The mesh is then circumferentially disposed around the mandrel as seen inFIG. 5F. A ribbon, wire, or other filament may be wrapped over the mesh to ensure that it contacts the mandrel.

FIG. 5Gillustrates the wire mesh disposed over the mandrel. The mandrel and mesh are then heat treated as described herein so that the wire mesh is set to take the shape of the mandrel. The mesh preferably comprises a nitinol material and is self-expanding, such that the mesh may be collapsed into a collapsed configuration for delivery, and the wire mesh may self-expand into an expanded shape which matches the mandrel and the aneurysm shape. After heat treatment is completed, the mesh and mandrel may be dip coated with a polymer, or the polymer or fabric cover310may be applied to the mesh using methods described herein or known to those of skill in the art. The polymer or fabric cover or membrane310may be resilient or flexible to withstand deformation as the mesh is collapsed and expanded, and is preferably impermeable to blood to prevent blood from flowing across the wall of the prosthesis. Radiopaque markers308or other indicator markers are optionally attached to the polymer or fabric cover or membrane and/or to the wire mesh. The personalized prosthesis or PSG is now complete and can substantially match the anatomy of the aneurysm. The personalized prosthesis, when deployed within the aneurysm after which it was modeled, can seat itself in the aneurysm, thereby anchoring the prosthesis in proper position and further excluding the aneurysm from blood flow, thus preventing endoleaks.FIG. 5Hillustrates the personalized prosthesis with markers308once the mandrel has been removed. The prosthesis can be loaded onto a delivery catheter or other delivery device and implanted at the site of the aneurysm as seen inFIG. 5G. Prosthesis delivery and implantation methods are described in further detail herein.

FIGS. 6A-6Cillustrate an exemplary embodiment of a personalized prosthesis that forms a new lumen for blood flow. The aneurysm may be imaged and the corresponding mandrel manufactured to substantially match the aneurysm shape, as described herein. Once the mandrel is fabricated, the mesh and/or polymer may be applied to the mandrel as described herein. In the embodiment shown inFIGS. 6A-6C, the resulting prosthesis502includes a main body section504that matches the size and shape of the aneurysm, and also includes an elongated neck portion506. As shown in nFIG. 6B, the elongated neck506may be invaginated as indicated by the arrows such that the elongated neck portion506becomes disposed inside the main body portion504. The space510between the neck portion506and the inside wall of the prosthesis502may be left as is, or it may be filled with a fluid, solid, or other material. The elongated neck portion506, which is preferably a cylindrically shaped tube, can now act as a lumen for blood flow therethrough. The free end508of the elongated neck506may be left as is, or it may be anchored to prevent flapping. Anchoring may be accomplished with a stent, sutures, or staples, or the elongated neck may be sized such that the blood pressure opens the free end up fully and lodges it against a downstream and inner portion of the prosthesis. The free end508may also be sealed with the prosthesis in case the space510is filled with a material.FIG. 6Cillustrates the personalized prosthesis ofFIG. 6Bdelivered into an infrarenal aortic aneurysm AA. This embodiment allows creation of a lumen which more accurately matches the natural blood flow path before the aneurysm enlarged the blood flow path. Delivery of the personalized prosthesis may be by any of the methods described herein.

In aneurysms extending over one or more side branch vessels, a mesh-only personalized prosthesis may be disposed over the ostium of the side branch without substantially blocking blood flow to the side branch. A personalized prosthesis with a polymer or fabric coating over a wire mesh may be used, but such a prosthesis may obstruct blood flow into the side branch vessels. For example, a juxtarenal aneurysm AA as seen inFIG. 7extends across part of the aorta A, and involves the renal arteries R. In this exemplary aneurysm, the iliac arteries I, external iliacs EI, internal iliacs II, and femoral arteries F remain unaffected by the aneurysm. In this case, implanting a conventional graft or a prosthesis comprising a polymer or fabric coating to exclude the aneurysm can obstruct blood from flowing into the renal arteries, resulting in damage to the kidneys. Thus, an improved and personalized prosthesis not only has a size and shape to match the anatomy of the treatment site, but also can accommodate for side branch vessels, or other side branch lumens and passageways.

FIG. 8illustrates an exemplary embodiment of a personalized prosthesis that can accommodate side branches such as the renal arteries. The personalized prosthesis702includes a wire mesh704and an optional polymer or fabric cover706as described herein. The prosthesis702may also optionally include radiopaque markers708to facilitate visualization and placement. The personalized prosthesis may be fabricated in a similar manner as described herein, and also include apertures or fenestrations710in a sidewall of the prosthesis that are in fluid communication with the central channel712of the prosthesis. The side apertures are positioned along the prosthesis so that they match the location of the side branch vessels or body passages such as renal arteries. The location of the apertures may be accurately determined based on the image obtained, such as a CT scan and the like. During manufacturing of the prosthesis, one or more additional mandrels that extend laterally away from the main forming mandrel may be coupled with the main forming mandrel at locations corresponding to the locations of the side branch vessels. The laterally-extending mandrels can maintain the apertures in the wire mesh, and also maintain the apertures once the mesh and mandrel are dip coated into a polymer, or when a polymer or fabric cover are otherwise applied to the mesh. The prosthesis702can then be loaded into a delivery catheter as described herein. The prosthesis can then be deployed using the radiopaque markers to guide the axial placement of the prosthesis along the aorta, such that the side apertures710align with the ostia of the side branch vessels.FIG. 9shows the prosthesis702deployed in the juxtarenal aneurysm ofFIG. 7, with the apertures710aligned with the ostia of the renal arteries R. Thus blood flow is not only maintained through the prosthesis across the aneurysm, but also to the renal arteries. While the filaments may partially cover the ostia, such a partial covering of the ostia with wire filaments generally would not significantly obstruct blood flow to the side branches.

FIGS. 10A-10Billustrate another embodiment of a personalized prosthesis that accommodates for the renal arteries as well as other side branch vessels. InFIG. 10Athe aneurysm AA is disposed in the aorta A and extends across the renal arteries R and also across other side branch vessels1402and1403that are between the iliac arteries I and the renal arteries R. The aneurysm is imaged as described herein, and a central mandrel matching the aneurysm is then fabricated. The location of the renal arteries and/or one or more side branch vessels may be determined based on one or more images of the aneurysm (e.g., CT scan images), or a digital data set created from the one or more images. Additional mandrels are laterally positioned where the renal arteries and the side branches are located. The mesh is then woven over the mandrel and around the side branch mandrels so that an aperture is maintained at their location. In alternative embodiments, the mesh is pre-woven and the loaded over the mandrel. The side branch mandrels are placed into the mandrel to push the filaments of the mesh away thereby creating and preserving openings for the renal or other side branches. After heat treating and other processing including putting an optional polymer or fabric coating over the mesh, a personalized prosthesis1404is produced as seen inFIG. 10B. Any of the mesh patterns disclosed herein may be used. The prosthesis includes apertures1406configured to match with the ostia to the renal arteries, and apertures1408and1409configured to match with the ostia to the other two side branches shown inFIG. 10A. The apertures1406,1408and1409are in fluid communication with the central channel of the prosthesis so that blood flow will remain unobstructed to the renal arteries or the side branch vessels. An optional radiopaque marker1410may also be included on the prosthesis in order to help align the prosthesis with the renal arteries and side branches during delivery. The radiopaque marker may include a long linear portion that indicates the longitudinal axis of the prosthesis. The radiopaque marker may be formed from a dense metal such as gold or platinum, or rhodium alloy that is coupled to the mesh. The renal arteries or other side branches themselves may be used during alignment by injecting contrast media through the vessels while visualizing the prosthesis and surrounding vessels under fluoroscopy or using other visualization techniques known in the art.

The personalized prostheses described herein preferably include a wire mesh that self-expands to the personalized shape. Various wire patterns may be used to create the mesh. For example,FIG. 11illustrates a mesh902having one or more filaments904which are spirally wound and an optional polymer or fabric cover906is applied to the mesh. This pattern of forming the mesh is advantageous because there is no overlap of the filaments, and the spiral pattern helps the mesh to be collapsed into a low profile for delivery.FIGS. 12A-12Fillustrate other exemplary mesh patterns.FIG. 12Aillustrates a mesh1002ahaving one or more filaments1004athat interweave with one another similar to traditional fencing wire or chicken wire, to form a single overlapping or twisted region1006a. The overlap region is preferably in every row and every column of the mesh where the filaments meet. The overlapping region forms a protuberance which may be advantageous since the protuberance may help embed the prosthesis into the tissue at the treatment site thereby helping to anchor the prosthesis. Having a single overlap of the filaments helps the filaments move relative to one another thereby allowing the prosthesis to be easily collapsed which is desirable during loading onto a delivery system and also helps to keep the profile of the prosthesis minimal. This is also advantageous since it allows the prostheses to expand and collapse in concert with the pulsatile nature of the blood as it flows through the aorta or other vessel. However, in some circumstances, the single overlapping or twisted region may not be secure enough to keep the mesh in its formed pattern or to provide adequate support to the aneurysm, especially when the prosthesis is under tension or compression because the wires in the mesh may slip or slide relative to one another. The prosthesis undergoes tension and compression during loading on a delivery system, during deployment, and after implantation due to the pulsatile nature of blood flow.

FIG. 12Billustrates an alternative embodiment of a mesh pattern that is more secure than the embodiment ofFIG. 12A. Mesh1002bhas one or more filaments1004bthat interweave with one another to form a double overlapping or twisted region1006b. The overlap region is preferably in every row and every column of the mesh where the filaments meet. The overlap region forms a protuberance similar to that inFIG. 12Aand thus may also be useful in anchoring the prosthesis. Having the double overlapped or twisted region secures the filaments together more tightly and thus helps prevents the filaments from slipping or sliding relative to one another when the prosthesis is under tension or compression. Thus the prosthesis retains its shape and provides more support than the embodiment inFIG. 12A. However, in some circumstances, the wires may still slip or slide relative to one another, thus further securing of the filaments may be needed.

FIG. 12Cillustrates still another embodiment of a mesh pattern which helps provide a stable mesh. The mesh1002chas one or more filaments1004cthat interweave with one another to form a triple overlapping or twisted region1006c. The overlap region is preferably in every row and every column of the mesh where the filaments meet. The overlap forms a protuberance similar to those previously discussed and therefore may aid in anchoring of the prosthesis. Having the triple overlap or twisted region secures the filaments together even more tightly than in the previous embodiments and thus the filaments are further constrained from slipping or sliding relative to one another when the prosthesis is under tension or compression. In some circumstances, having the triple overlap region secures the filaments together tightly enough that they cannot move at all relative to one another when the prosthesis is under tension or compression. If the filaments cannot move at all relative to one another, this prevents the prosthesis from axially or radially expanding or contracting which interferes with its ability to be loaded in a collapsed configuration onto a delivery system, from expanding radially outward upon deployment, or from expanding an contracting in concert with the vessel wall due to pulsatile blood flow.

FIG. 12Dillustrates a preferred embodiment of a hybrid mesh pattern that secures the filaments together securely so that the prosthesis holds its shape and provides good support during tension and compression, and yet at the same time still allows some movement between the filaments so that the prosthesis can expand and contract. Mesh1002dhas one or more filaments1004dthat interweave with one another to form an alternating pattern of a triple overlap or twisted region1006dfollowed by three double overlap or twisted regions1008d. The pattern then repeats itself horizontally, and the next row shifts by one twist to the right. Thus the triple twist in one row is offset from the triple twist in the next row, and is followed by another set of double twisted or overlapped regions1008d, and then the pattern repeats. The pattern repeats so that everywhere the filaments overlap with one another, there is either a double or triple overlap or twisted region. The overlap region forms a similar protuberance as previously described which may be useful for anchoring the prosthesis. This hybrid weave has the advantages of both the double and triple overlap weaves previously described. Thus, the triple overlap regions secure the filaments together to minimize their movement relative to one another during compression or tension and thus the prosthesis holds its shape and provides good support, while at the same time the double overlap regions allow some movement of the filaments relative to one another thereby allowing the prosthesis to axially and radially expand and contract during delivery, deployment, and after implantation. The weave preferably minimizes or substantially eliminates axial expansion and contraction while allowing radial expansion and contraction.

FIGS. 12E-12Fillustrates expansion and contraction of a personalized prosthesis such as those described above using the weave ofFIG. 12D. Without being bound by any particular theory, it is believed that the filaments will remain tightly engaged with one another when the prosthesis1002dis under tension such as while the heart is in systole as seen inFIG. 12Eand represented by arrows1018d. Here, the filaments1004dremain tightly wound together in both the double overlap region1008das well as the triple overlap region1006d. The gap1012dbetween adjacent filaments wound together in a region1008dmay be represented by distance Si and the pitch1010dor spacing between adjacent columns of wound filaments may be represented by distance P1during systole. When the prosthesis is compressed such as when the heart is in diastole, as indicated by arrows1020dinFIG. 12F, the pitch or spacing1014d, represented by distance P2, between adjacent columns of wound filaments generally decreases relative to the expanded configuration as shown inFIG. 12E. Moreover, the gap1016dbetween adjacent filaments wound together in a double overlap region1008dincreases relative to when the prosthesis is in the expanded configuration thereby allowing the filaments to slide relative to one another. Adjacent filaments wound together in a triple overlap region1006dremain twisted together and there is substantially no relaxation, such that the gap between the adjacent filaments does not change substantially. Thus, when viewing the prosthesis laying on its side with its longitudinal axis horizontal, the triple-double-double-double horizontal weave pattern accommodates the motion of the aorta vessel wall caused by the pulsatile motion of the blood flowing through it. Of course, one of skill in the art will appreciate that this particular pattern is not intended to be limiting. Other patterns may be used including any combination or permutation of the single, double, triple, or more than three overlapping regions.

FIGS. 12G and 12Hshow additional details of the intertwining of the wire filaments that make up the wire mesh of the personalized prosthesis. Typically, two neighboring filaments33and34are twisted together against each other in a manner35. A plurality of twisted portions collectively defines a cell36, and the plurality of the cells36in turn form the frame14. The cells may have a substantially hexagonal shape comprising six sides. The twist35can be formed by twisting the neighboring filaments33and34either in a clockwise (cw) direction as shown inFIG. 12G, or a counterclockwise (ccw) direction as shown inFIG. 12H. The direction of the twists can be clockwise for all the twists comprising the wire frame14. Conversely, all the twists forming the wire frame14can be of counterclockwise direction. Alternatively, the wire frame14can be constructed with wire twists of any other orderly or random mix of cw and ccw twist directions. The direction of the twists may influence delivery and implantation of the device, particularly the rotational orientation of the prosthesis with respect to the lumen when implanted. Thus, the direction of the twists of the prosthesis may be specifically configured to enable self-alignment or self-orientation of the prosthesis in the proper rotational orientation when implanted in the lumen, as described in further detail herein.

The filaments on the proximal and distal ends of the prosthesis may be terminated in any number of ways.FIG. 13illustrates one exemplary embodiment. The prosthesis1602has the triple-double-double-double weave pattern ofFIGS. 12A-12Fdescribed above. The filaments may terminate in an end region1604by twisting the filaments such that they overlap one another four times. One of skill in the art will appreciate that this is not intended to be limiting and the number of overlapping regions may be one, two, three, four, five, six, or more. Additionally, the ends may remain extending axially outward to help anchor the prosthesis in tissue by partially piercing the tissue, or the ends may be formed into curves, loops, or other shapes to prevent sharp ends from protruding and causing tissue trauma. This prevents the filaments from moving relative to one another. Additionally, the end region1604may then be bent slightly radially outward1606to form a skirt or flanged region which flares outward and thus can embed into the vessel wall to help anchor the prosthesis.

In the embodiments ofFIGS. 12A-12F, the weave pattern has been described when the prosthesis is sitting on its side such that the longitudinal axis of the prosthesis is generally horizontal. Thus, the weave pattern is generally parallel to the longitudinal axis, and the filaments are weaved together in a horizontal pattern across the prosthesis and with a vertical orientation. In still other embodiments, the weave pattern ofFIGS. 12A-12Fmay be rotated ninety degrees so that the filaments are weaved an orthogonal direction.FIG. 14illustrates an exemplary embodiment of the weave pattern inFIG. 12Arotated ninety degrees. The weave is illustrated with the prosthesis laying flat on its side with its longitudinal axis generally horizontal. Thus, mesh1202includes a plurality of filaments1204that are weaved together to form a single overlap or twisted region1206. Other aspects of this embodiment generally take the same form as inFIG. 12A. The other embodiments described previously may also be weaved in a pattern that has been rotated ninety degrees. Any of the mesh patterns described herein may be formed into a round tubular member or the mesh may be woven into a flat sheet and the ends may be joined together to form a round tubular member. Additionally wires or filaments of different diameters may be combined with one other, or a single diameter may be used throughout a single mesh prosthesis in order to obtain desired mechanical properties.

FIG. 15illustrates still another pattern for the mesh1102. This pattern has one or more filaments1104woven into an undulating pattern. Adjacent rows of the undulating filaments are tied together with a wire, suture, or other tie1106. Optionally, one or both ends of the tie1106may be left uncut to form a barb1108that can also be used to help anchor the prosthesis to tissue at the treatment site. Any of these wire mesh patterns with anchoring or without anchoring may be used in any of the embodiments described herein.

FIG. 16illustrates yet another exemplary embodiment of a mesh. The mesh1302includes one or more filaments1304which are formed into an undulating pattern having peaks and valleys. The peaks and valleys in one row of the mesh may overlap with the valleys and peaks of an adjacent row of the mesh. The overlapping portions may then be welded1306together to keep the filaments coupled together. In alternative embodiments, welds may be any combination of the previous mesh embodiments.

The structure of the prosthesis is further illustrated byFIGS. 17A through 21B. As shown inFIGS. 17A and 17B, a prosthesis1402, which may be any of the prostheses disclosed herein, is deployed at its intended location in the aneurysm AAA. The area of the AAA designated as1404, which may be an area in the vicinity of an SB of the AAA as shown inFIG. 17B, is further described below.

Portion1404of prosthesis1402ofFIG. 17A or 17Bis shown in an enlarged view inFIG. 18. Prosthesis1402consists of a grid structure made of wires1406as described herein. The wire grid is covered by a membrane1410. The inner (lumen) side of the prosthesis1402is covered with a lining1412. The smooth surface lining1412may be made of a low friction bio-compatible material such as teflon, silicone, or a metal film, which allows for smooth flow of blood therepast.

FIG. 19shows a further enlarged view of a longitudinal section of the structure of the prosthesis1402. The wires1406of the grid are interwoven, such as in a ‘chicken wire fence’ manner (as described herein), and appear as single wire1406or in an overlapping configuration1408. A membrane1410covers the wire grid conformally. As shown in detail inFIG. 19, the inner (lumen) side of the prosthesis1402is smooth whereas the outer side of the said prosthesis is textured having a series of peaks and valleys.

Shown further inFIG. 20in an enlarged view, the inner surface of the membrane covering prosthesis1402has been disposed with a lining1412. The lining constitutes a low friction surface such as Teflon, silicone, metal film or any other suitable bio-compatible material. The lining can be deposited by liquid dipping or spray deposition techniques known in the art. Inner lining1412can also be made of a biocompatible, vapor-deposited metal film such as gold or stainless steel. The lining can also be disposed on the outer surface1418of the prosthesis1402. The outer surface1418of the prosthesis1402is textured on the outside while the prosthesis1402has a smooth lining1412on the inside. The smooth lining1412presents a smooth surface for blood flow. The textured outer surface1418helps in the rotational motion as described herein.

FIG. 21Ashows an enlarged view of the prosthesis1402appositioned against the wall1414of the blood vessel shown inFIG. 17A. The textured outer surface1418of the prosthesis1402comes against the inner surface1424of the tissue1420of the AAA. This action aids in a firmer apposition of the prosthesis1402against the tissue1420which is a desirable outcome of the deployment of the prosthesis1402in the aneurysm AAA. Further, the textured surface creates the interstices1416which serve as pockets for the blood to reside in. The trapped blood eventually forms a thrombus thus aiding in the embedding of the prosthesis1402against the AAA.

FIG. 21Bshows an enlarged view of the prosthesis1402appositioned against the wall1426of the blood vessel1420shown inFIG. 17B. The textured features of the outer surface1418of the prosthesis1402are maintained in a firm apposition against the inner surface1424of the tissue1420of the AAA. In particular, in some cases, the outer surface of the prosthesis can be placed in firm apposition against the ostium of a side branch vessel SB. The firm apposition of the prosthesis1402against the inner surface1424, together with the thrombus formation in the interstices1416, assures that the blood flow to the side branch SB is blocked. By virtue of this configuration, the condition of type II endoleaks is eliminated.

When the prosthesis1402is in conformal contact with the AAA, the aneurysmal pocket28as shown inFIG. 2is eliminated, and blood flow is directed through the lumen of the prosthesis1402. The membrane1410of the prosthesis1402is of sufficient strength to withstand the pressure of the flowing blood. The pressure is entirely contained within the prosthesis1402, and the wall1426of the AAA is relieved of the pressure. The AAA is thus stabilized against the force of blood pressure, and the risk of AAA enlargement and eventual vessel rupture is significantly reduced or eliminated.

As described herein, the process of manufacturing the prosthesis involves a sequence of steps which comprise individual tolerances for sizes. For example, the machining and 3D printing processes used in forming the mandrel typically have plus-minus tolerances. As a result of the stack up of various tolerances, the shape of the resulting prosthesis may not completely conform to the shape of the aneurysm. Complete conformity can be important as it may reduce the risk of forming ‘pockets’ of mismatch between the outer surface of the prosthesis and the inner wall surface of the aneurysm. The pockets can provide the spaces for endoleaks, which are persistent problems with current cylindrical stent grafts is use today. Therefore, it would be desirable to provide a personalized prosthesis which is designed and built to self-adjust in shape to completely and faithfully conform to the inner wall of the aneurysm. Preferably, the personalized prosthesis provides protection of the aneurysm against rupture while eliminating the endoleaks that can result with prior cylindrical stent grafts (e.g., ofFIG. 2).

Exemplary embodiments described herein illustrate structures and methods of making the structures wherein the personalized prosthesis is self-adjusting to the shape of the blood flow lumen. This is preferably accomplished by making the prosthesis appropriately oversized with respect to the lumen, and providing a wire twist pattern for the frame of the prosthesis which can self-adjust to the shape of the lumen. The wire frame of the prosthesis can be fabricated from a twist pattern made from the twisting of neighboring wire filaments. As described herein, some ordered, unique patterns can provide the desired properties of self-adjustment when the prosthesis is specifically manufactured for a given aneurysm pocket. The wire frame constituting the personalized prosthesis can be configured to have sufficient hoop strength to maintain firm apposition against the lumen wall. In addition, the wire frame can be configured to have a sufficiently small collapsed profile to make it suitable for containment in a delivery catheter for delivery and deployment in a percutaneous technique.

FIG. 22shows the overlay of a mandrel2008in a lumen2000in an abdominal aortic aneurysm AAA. As described herein, as the CT data are used through the various steps towards the creation of the personalized prosthesis, there is a stack up of tolerances of sequential process steps which results in slight ‘mismatches’2012and2014of the mandrel shape compared to the shape of the lumen of the aneurysm. As a result, the mandrel2008has a slightly different shape than the lumen2000where the surface of the mandrel2008does not perfectly match the lumen shape2010. The resulting mismatch2014in the vicinity of the side branch SB, for example, provides for a potential pocket for the eventual creation of an endoleak.

A solution for overcoming the mismatch due to tolerance stack up is to fabricate a mandrel which is slightly oversized to overcome the mismatch2014, and to provide a wire frame structure which has the ability to change shape and self-adjust for the mismatches like2012and2014. The resultant prosthesis can have the ability to reduce in size in response to being constrained within a lumen having a smaller size, and thereby self-adjust to the contour of the inner wall of the aneurysm.

FIG. 23shows a mandrel2016which is slightly larger than the mandrel shape2008based on the internal geometry of the aneurysm as determined by the CT scan and the attendant translational tolerance stack up. The mandrel2016can be larger only in the x-y direction, and not in the z direction. The mandrel2016may have a diameter that is oversized relative to the shape2008based on the internal geometry of the treatment site by about 2% to about 40%, about 2% to about 15%, about 5% to about 15%, or about 5% to about 10%. For example, for an aneurysm lumen diameter of 50 mm at a given cross-section, the mandrel may be 55 mm (10% larger) in diameter at that location. The extra 5 mm can be used in adjusting for the mismatches like2012and2014. The oversizing of the mandrel (and therefore the prosthesis) can position the prosthesis firmly against the ostium of the side branch SB thereby eliminating the pocket formed by mismatch2014which could give rise to an undesirable endoleak.

FIG. 24shows an oversized, personalized wireframe prosthesis2018conformal to the oversized mandrel2016. The prosthesis is thus made oversized with respect to the lumen representation2008. The personalized prosthesis may provide for the apertures or fenestrations2020and2022corresponding to the renal artery RA ostia, using the data provided by the CT scan as described herein. The inferior portion2026of the prosthesis2018, which is inferior to the renal arteries RA, can be covered with a membrane of a thin plastic material such as teflon, silicone, and the like. The cover or membrane may be only on the inner surface or outer surface of the prosthesis, or it may be on both surfaces. The superior portion2024of the prosthesis2018, which is superior to the renal arteries RA, is preferably not covered with a membrane. The wire frame in the superior portion may be left uncovered. The purpose for this is so that, over time, the wire frame gets embedded in the endothelial lining of the aortic lumen. This action can further secure the prosthesis in the aneurysm.

FIGS. 25A to 25Gshow various wire twist patterns which can be used for fabricating the wire frame of the prosthesis. By way of terminology, a ‘twist’ is a pattern where two neighboring wire filaments are wound against each other. A ‘loop’ is defined as one wind of the neighboring wires.

FIG. 25Ashows a pattern where the neighboring wires cross over each other. In this case the wires do not form a loop. The result is a braided structure which is of a cylindrical shape. This structure may not be suitable for percutaneous deployment in the aneurysm because that the structure can elongate substantially when confined inside a slider tube of the delivery catheter. In addition, its hoop strength may not sufficient to be effective in maintaining a firm apposition of the prosthesis against the aneurysm lumen.

FIG. 25Bshows a twist pattern in which two neighboring wires are wound against each other once to form one loop. The entire prosthesis is made from these single loops. This pattern also has relatively poor hoop strength and may not be suitable for making an effective functional prosthesis.

FIG. 25Cshows a twist structure involving two loops formed by winding of the two neighboring wires. The prosthesis made from this pattern of two loops also has relatively poor hoop strength, and therefore may not be suitable for a functioning prosthesis.

FIG. 25Dshows a twist pattern which employs three loops of neighboring wires. This structure has better hoop strength, but when collapsed, it forms a relatively larger profile, for example compared to the structures ofFIGS. 25A-25C. Also, it does not have the ability to self-adjust for any shape mismatch, as described further herein.

FIG. 25Eshows a preferred embodiment of the present wire pattern. The twist pattern consists of a combination of two and three loops of neighboring wire filaments. More specifically, the pattern has a combination of one twist of three loops, followed by three two-loop twists, forming a group of four twisted wire pairs in a 3-2-2-2 loop configuration. Then the group of the four twist pattern repeats along a cylindrical locus. This pattern is termed as “41”. The first digit, namely, “4” refers to the pitch count of the twists, and the second digit, namely, “1” refers to the twists which have three loops. Thus a 41 pattern has a pitch2028of four (4) twists where one (1) twist has three loops and the remaining three twists have two loops, also described as a “3222” pattern. In this nomenclature, pattern shown inFIG. 25Dwould be termed as “44”, where the pitch consists of four (4) twists, and all four (4) twists have three loops each.

It is important that, in order to obtain the best functional prosthesis, the pitch2028of four (4) twists be offset by at least one twist in the next cylindrical locus as shown inFIG. 26E. Similarly, the next circumferential twist pattern will be shifted to the right by one twist.

FIG. 25Fshows a twist combination which, in the above nomenclature, is termed a “31”. It has a pitch2030of three (3) twists. Of this, one (1) twist consists of three loops and the following two twists consist of two loops each, forming repeating groups of three twisted wire pairs in a 3-2-2 loop configuration.

We have fabricated more than 100 patterns of various combinations and tested the resulting hoop strength as well as the ability of the wire frames to self-adjust. The “41” pattern was found to be optimal in terms of hoop strength, ability to self-adjust in shape, and ability to be confined into a sufficiently small delivery system suitable for percutaneous delivery and deployment of the prosthesis in the aneurysm space. Optionally, the prosthesis may comprise two or more regions having different wire frame patterns, such that the two or more regions have different hoop strengths and/or ability to self-adjust to different extents. For example, a prosthesis may be formed to have variable hoop strength along a longitudinal axis of the prosthesis, by having wire frame patterns of various hoop strengths arranged along the longitudinal axis.

FIG. 26shows a cross-sectional view of prosthesis2018along the line LL ofFIG. 24. By way of example, the prosthesis2018consists of 32 filament wires forming 16 nodes. The prosthesis also consists of a membrane2036. In free space, the loops are tightly wound against each other. Nodes2032consists of a two-loop twist, and nodes2034consists of a three-loop twist. The 16 nodes are divided into four pitches2028of four twists each. The lumen of the aneurysm is depicted as2038. As seen in this figure, the prosthesis2018in its free space configuration is larger in size than the lumen2038. As described herein, the prosthesis2018can be fabricated to be larger than the lumen2038into which the prosthesis is to be delivered. When the prosthesis is deployed in the lumen, the loops of the twists can automatically adjust in response to confinement within the lumen2038having a circumference smaller than that of the prosthesis2018.

FIGS. 27A and 27Bshow the details of the adjustment of the loops of a given twist in response to being confined to a smaller circumference.FIG. 27Ashows the 41 pattern of the prosthesis in free air. The three-loop twists2040are locked against each other by virtue of its construction, but the two-loop twists2042are free to move the loops relative to each other. As the prosthesis is deployed in the smaller space of the lumen, the two-loop twists2042adjust by opening up against each other. In free space, the distance2044between the adjacent twists is shown inFIG. 27A. The two-loop twists have loops2046and2048. Even though the wire filaments are tightly wound around each other, the outer edges of the wire filaments are distance2050apart from each other.FIG. 27Bshows the configurations of the loops of the twists as the prosthesis2018is deployed in the smaller confines of the lumen. The distance2052between the adjacent twists is now correspondingly smaller than the free-air distance2044. The first two-loop twist2054, adjacent to the three-loop twist2040, consists of an upper loop2056and a lower loop2058. The second two-loop twist2060, disposed in the middle between two adjacent two-loop twists, similarly consists of the upper loop2062and a lower loop2064. The third twist2066consists of an upper loop2068and a lower loop2070. When the prosthesis2018having the free-air distance2044between adjacent twists, as shown inFIG. 27A, is deployed in the smaller confines of the lumen2038, loops of the twists make the appropriate adjustments, resulting in the smaller distance2052between adjacent twists as shown inFIG. 27B.

The adjustments of the loops of the twists may be symmetrical. For example, as shown in first two-loop twist2054ofFIG. 27A, the upper loop2056may open up to an inter-wire spacing of2072, while the lower loop2058stays at an inter-wire spacing2074of a tight twist (same as the inter-wire spacing2050of the loops in the free space configuration, shown inFIG. 27A). As shown in the second or middle twist2060, both the upper loop2062and the lower loop2064may open up to substantially equal inter-wire distance of2076and2080, which may be greater than the inter-wire distance2050of the loops in the free space configuration. Finally, as shown in the third twist2066, the upper loop2068may remain closed to an inter-wire distance of2082(same as the tight wound twist2050of free space configuration), while the lower loop2070may open up to a spacing2084greater than the inter-wire distance2050of the loops in the free space configuration. The loops of three-loop twists2040adjacent the two-loop twists2074,2080, and2084may not open up, remaining tightly wound.

The difference between the inter-twist distance2044in the free space configuration and the inter-twist distance2052in the lumen-confined configuration may be accounted for by the increase in the inter-wire spacings2072,2076, and2084when the loops of the two-loop twists open up. The extent to which a loop of a two-loop twist opens may be limited by the locking of one of the two loops while the other loop opens up to a finite distance. This limit in the extent to which the loops can open in turn places a lower limit on the diameter of the prosthesis to which the wire mesh can self-adjust. Such a limit in the extent to which the prosthesis can self-adjust to a smaller diameter can be advantageous, as the prosthesis needs to maintain an appropriate hoop strength to provide firm apposition of the prosthesis against the aneurysm wall. The cross-over pattern ofFIG. 25Aor the single-loop twist frame ofFIG. 25Bprovide no definite limit or insufficient limit to the decrease in prosthesis diameter, as these two patterns do not have a ‘locking’ loop. Conversely, the three-loop twist of the 44 configuration, as shown inFIG. 25D, does not allow for the opening of the loops as all three loops are tightly wound against each other. Thus a hybrid configuration such as the 41 configuration shown inFIG. 25E(3-2-2-2 loop twists) can provide for the optimal configuration for the fabrication of a preferred structure of a self-adjusting effective prosthesis. This prosthesis can self-adjust against tolerance variations in spacing while providing the necessary hoop strength to maintain firm apposition against the aneurysm lumen wall to prevent endoleaks and reduce or eliminate the risk of vessel rupture.

The two-loop twists open up along the circumferential plane for necessary self-adjustment needed to accommodate the size differential between open air and confined configurations of the prosthesis. Therefore, the mandrel need be made larger only in the circumferential plane (x-y plane of theFIG. 23). The mandrel may be oversized by a fixed percentage in all dimensions, or by varied percentages in different dimensions. A prosthesis made from a mandrel which is oversized in all dimensions will not have complete conformity as it does not have any mechanism to accommodate for the size differential in the z direction.

FIG. 28shows the deployment of a 44 (3-3-3-3 loop twists) structure prosthesis2018in the lumen2036. The dotted line configuration2086represents the prosthesis2018in free space. Since the three-loop twists2114do not do not allow for the opening of the loops, they remain tightly wound in a manner2116. As a result, the prosthesis is forced to buckle up at one or more locations, forming bucked spacings2088and2090to accommodate the smaller confines of the lumen2036. This is an undesirable configuration of the deployed prosthesis as the buckled spacings2088and2090allow for blood flow channels giving rise to potential endoleaks. In addition, the conformity of the prosthesis2018against the lumen2036is compromised.

FIG. 29shows the prosthesis2018of 41 (3-2-2-2 loop twists) pattern deployed in the lumen2036. The free space shape2092of the prosthesis is shown in a dotted line configuration. Prosthesis2018self-adjust to a smaller space2036of the lumen by allowing the individual twists of two loops to open up to accommodate the corresponding reduction in the circumferential dimension. In the free space configuration2092, all the wire twists are tightly wound and are in close proximity to each other as depicted by twist2108having an inter-wire distance2094. In the lumen-confined configuration of prosthesis2018, the three two-loop twists2096,2100, and2104open up in an asymmetrical fashion or in a symmetrical fashion as described in detail with reference toFIG. 27B. First, the upper loop of the first two-loop twist2096opens up to an inter-wire spacing of2098. Next, both loops of the second two-loop twist2100open up to an inter-wire spacing of2102. Last, the lower loop of the third two-loop twist2104also opens up to an inter-wire spacing of2106. The next twist2108consists of three loops, and as explained herein, it remains tightly wound in a manner2110. This symmetrical pattern may repeat for the next set2112of four 3-2-2-2 loop twists.

The prosthesis2018of a 41 configuration can thus maintain its conformal apposition against the lumen2036, by self-adjusting to closely match the shape and circumferential dimensions of the lumen when deployed. The self-adjusting nature of the prosthesis can provide improved protection against endoleaks and hence risk of vessel rupture, compared to configurations that do not allow substantial self-adjustment of the prosthesis shape and dimensions (e.g., the prosthesis of a 44 configuration as shown inFIG. 28).

FIG. 30shows the prosthesis2018of a 41 configuration (3-2-2-2 loop twists) deployed in the lumen2036. The free space configuration of the said prosthesis is shown as2092. The individual adjustments of the twists are shown. The repeat pattern2118is made of a set of 3-2-2-2 loop twists. The first twist2120consists of three loops and does not open up substantially in response to the prosthesis being confined to a smaller space of the lumen. Next, the first two-loop twist2122adjusts such that the upper loop of the said twist opens up while the lower loop remains tightly wound. The second two-loop twist2124has both loops opened, and the third two-loop twist2126has the lower loop opened up while the upper loop of this twist remains tightly wound. This pattern repeats for the next set of four twists. The opening of the two-loop twists accommodates automatically as needed to the confines of the lumen.

The opening of the loops may not be symmetrical in all cases. For example, in a situation where there may not be a large mismatch, as shown at locations2128and2130, the opening of the two-loop twists may be somewhat random, but sufficient to account for the self-adjustment.

FIG. 31shows the placement of a personalized or custom-shaped prosthesis2132in an AAA, the prosthesis made to specifications provided by the corresponding CT scan without any oversizing. Such a prosthesis may be fabricated from the non-oversized mandrel2008ofFIG. 22. As the prosthesis2132is deployed in the AAA, the apposition of the prosthesis2132against the lumen wall2134may not be optimal, forming pockets of mismatch2136,2138, and2140at which locations the circumferential dimension of the non-oversized prosthesis2132is smaller than the circumferential dimension of the lumen wall2134. Because the prosthesis as described herein is manufactured in its maximally expanded configuration, the non-oversized prosthesis is unable to expand any further when deployed to accommodate the spacings between the fully-expanded prosthesis and the lumen. These pockets are undesirable in the sense that they can provide for the leak of blood into the pockets. For example, the pocket2136in the vicinity of the ostium of the side branch SB can be a location for an endoleak to develop. The result of the endoleak is that the aneurysmal pocket keeps on enlarging, thereby increasing the risk of an aneurysm rupture.

FIG. 32shows the deployment of the oversized, self-adjusting personalized prosthesis2018in the AAA. As described herein, this design and construction of the prosthesis can provide complete conformal apposition of the prosthesis against the wall of the lumen2134, by enabling self-adjustment of the shape and dimensions of the prosthesis to match the shape and dimensions of the lumen. The oversizing of the circumferential dimensions of the prosthesis eliminates pockets of mismatch wherein the prosthesis is smaller than the lumen. Instead, in locations of mismatch between the prosthesis and the lumen, the dimensions of the prosthesis in its free-space configuration are now greater than the dimensions of the lumen, and the prosthesis is able to self-adjust at these locations by virtue of the opening of twist loops as described herein. The pockets of mismatch shown inFIG. 31, which can potentially lead to the development of endoleaks, are now eliminated or minimized, by the adjustment of the wire frame structure of the prosthesis to accommodate the exact geometry of the lumen. Thus, a more definitive treatment for the containment of the aneurysm is delivered.

While the functionality and use advantages of the oversized, self-adjusting personalized prosthesis are described herein primarily in reference to a 41 (3-2-2-2 loop) twist configuration, the oversized personalized prosthesis may comprise any appropriate wire frame construction that allows for the self-adjustment of prosthesis shape and dimensions. For example, an oversized prosthesis comprising a 31 (3-2-2 loop) twist configuration, as shown inFIG. 26F, can also serve as an effective, self-adjusting implant. In addition, any other combination of three-loop twists together with zero (i.e. braid), one, or two loop twists can also work for the intended oversized prosthesis. A twist network solely comprising three or more loops may have no or limited ability to adjust in size, and a prosthesis made of such a twist network would therefore have no or limited ability to self-adjust to the more confined space of a lumen. Numerous prostheses having various wire frame constructions have been fabricated and analyzed, and of the constructions studied, an oversized prosthesis made in a 41 configuration as described herein was shown to have the best attributes of self-adjustment, hoop strength, and apposition conformity, while having an acceptably small collapsed profile suitable for percutaneous delivery and deployment in the aneurysm.

The self-adjusting attribute of an oversized personalized prosthesis as described herein is also advantageous in maintaining complete apposition of the prosthesis against the tissue in a dynamic situation, such as during systolic and diastolic conditions of pulsatile blood flow. During the systolic part of the pulsatile cycle, the blood pressure in the aneurysm lumen is higher and the resulting diameter of the aneurysm lumen is larger. Conversely, during the diastole, the pressure of blood is lower resulting in a smaller lumen size. These dynamic variations can be automatically accommodated for by the built-in attribute of self-adjustment of the prosthesis.

FIGS. 33A-33Fillustrate an exemplary method of delivering a personalized prosthesis that is fabricated to match the patient's anatomy at the treatment site, as described herein. The personalized prosthesis is preferably fabricated using the methods described herein. This exemplary method is directed at treatment of an aortic aneurysm, but could also be used to treat aneurysms in other parts of the body such as a cerebral aneurysm, or other body cavities such as a stomach, bladder, etc. The method could also be used to treat normal or presymptomatic tissue of a patient at risk of developing an aneurysm or at early stages of development of an aneurysm.

FIG. 33Aillustrates an infrarenal aortic aneurysm AA in a portion of the aorta inferior to the renal arteries R. In this embodiment, the aneurysm does not extend into the iliac arteries I, external iliac arteries EI, internal iliac arteries II, or femoral arteries F. Thus, in this case the repair of the prosthesis does not need to extend past the aortic bifurcation into the iliac arteries I. However, in a situation where the diseased or damaged tissue extends past the aortic bifurcation, a similarly personalized prosthesis may be fabricated using similar methods described above. The prosthesis may be a single piece or it may be modular and assembled in situ. InFIG. 33Ba standard guidewire GW is inserted by surgical cutdown or percutaneously (e.g. using the Seldinger technique) into a femoral artery and then advanced so that the distal tip of the guidewire is positioned beyond the location of the aneurysm.

A delivery device such as a catheter402carrying the prosthesis can then be advanced over the guidewire GW so that the distal portion404of the delivery catheter402is positioned beyond the location of the aneurysm and preferably is upstream or superior to the proximal end (closest to the heart) of the aneurysm, as illustrated inFIG. 33C. Now referring toFIG. 33D, the delivery device may include an inner shaft409which carries the prosthesis406, and an outer sheath403disposed over the prosthesis to constrain the prosthesis from expansion during delivery. The delivery device may have one or more radiopaque markers (not shown) or other indicators to facilitate visualization, alignment, and delivery of the prosthesis, or optional radiopaque markers or other indicators on the prosthesis itself may be used to help position the device. Once the delivery catheter is appropriately positioned relative to the aneurysm, the outer sheath403may be retracted proximally (toward the physician operator), or from a far end of the prosthesis to a near end of the prosthesis (with respect to the operator), to expose the personalized prosthesis406having a mesh408and polymer cover410. When referring to the catheter, the term proximally refers to a position closest to the physician operating the catheter, and distal refers to a position furthest away from the physician operating the catheter. When referring to the aneurysm or the prosthesis, a proximal portion of the aneurysm or prosthesis is the portion closest to the heart (also referred to as upstream), and the distal portion of the aneurysm or prosthesis is furthest away from the heart (also referred to as downstream). The prosthesis406is a personalized prosthesis or PSG that has been manufactured to match the anatomy of the treatment site using the methods described herein. The prosthesis406may be any of the embodiments of personalized prostheses described herein. Retraction of the outer sheath403as indicated by the arrows inFIG. 33Dremoves the constraint from the prosthesis406thereby allowing the prosthesis to progressively self-expand into engagement with the walls of the aorta upstream of the aneurysm. As the outer sheath is retracted, an upstream or far end portion412of the prosthesis406radially expands outward into engagement with the aneurysm. The outer sheath403is further retracted as indicated by the arrows inFIG. 33E, until the entire prosthesis406is free of a constraint and thus the prosthesis406radially expands into engagement with the walls of the aneurysm and preferably above and below the aneurismal sac as well. Once the prosthesis has been delivered, the delivery catheter and guidewire may be removed from the patient leaving only the prosthesis406behind, as seen inFIG. 33F. Because the prosthesis406has been personalized to match the contours of the aneurysm, the prosthesis can self-expand to substantially fill the entire aneurismal sac and the prosthesis can engage the walls of the aneurysm over the entire treatment region. Further, as described herein, the prosthesis can be configured to self-adjust in response to any mismatches between its shape in the expanded configuration and the actual shape of the inner wall of the aneurysm, as well as self-orient to rotationally align its shape with the shape of the aneurysm.

Filling the entire aneurysm sac and having engagement of the prosthesis with the walls of substantially all of the aneurysm securely anchors the prosthesis in position, thereby preventing migration of the prosthesis and also ensuring good sealing between the prosthesis and the vessel. High conformity between the prosthesis and the walls of the aneurysm can prevent endoleaks and thus effectively exclude the aneurysm from blood flow, thereby alleviating pressure on the weakened walls of the aneurysm and preventing further dilation of the aneurysm. The personalized prosthesis can thus reinforce the aneurysm. Additionally, as shown inFIGS. 1G and 1H, some aneurysms may comprise mural thrombus formed on the walls of the aneurysm. Implanting a personalized prosthesis that matches the contours of the aneurysm helps to trap any mural thrombus between the prosthesis and the aneurismal wall, thereby preventing the mural thrombus from embolizing. Additionally, endothelial cells can cover the prosthesis and further facilitate anchoring of the device in position. Endothelialization generally begins about two weeks after implantation, and is substantially complete after approximately two months.

No new lumen is created in the embodiment of the prosthesis illustrated inFIGS. 33A-33F, and the blood can flow through a path that is substantially similar to its original path through the aneurysm, but while contacting the walls of the personalized prosthesis rather than the walls of the aneurysm. However, in some circumstances, it may be beneficial to create a new lumen for blood flow, as shown and described with reference toFIGS. 6A-6C. The new lumen may further prevent exertion of blood pressure against the walls of the aneurysm, or may restore natural blood flow or hemodynamics back to, or close to pre-aneurismal conditions.

In the embodiment ofFIGS. 33A-33Fa single prosthesis is delivered to the aneurysm.

However, in other embodiments, more than one prosthesis may be delivered. Delivering multiple prostheses can facilitate the delivery process since a single, low profile device may first be delivered, and additional prostheses may then delivered on top of one another, or axially spaced apart from one another in order to provide the desired coverage and support.

FIGS. 34A-34Billustrate the delivery of two personalized prostheses1504and1506. The prostheses may be delivered in substantially the same manner as previously described above, one after the other. A first personalized prosthesis1504may be delivered to the aneurysm AA and allowed to expand into engagement with the wall1502of the lumen. A second personalized prosthesis1506may then be serially delivered after delivery of the first prosthesis, such that the second prosthesis sits inside the first prosthesis1504.FIG. 34Billustrates a cross-section taken along the line B-B inFIG. 34A, and shows the two prostheses adjacent one another within the aneurysm. Such a configuration can provide greater support to the aneurysm and allows two lower profile prostheses to be delivered instead of a single higher profile device. Endothelialization of the prostheses can help to further anchor the prostheses into position. Multiple prostheses may be stacked inside one another as shown inFIGS. 34A-34B, and/or they be placed end to end to cover a longer treatment region.

FIG. 35Ashows the distal portion38of a delivery catheter system (DC) suitable for incorporation with embodiments. The system comprises a multilumen tube40. The central lumen42provides for a passageway for the guidewire tube44. A guidewire46traverses through the lumen48of the guidewire tube44. Other lumens50of the multilumen tube40provide for passageway for the purse string pull wires52. At the distal end of the DC, a nosecone54is attached to the guidewire tube44by means of the adhesive56. The nosecone54allows an atraumatic movement of the DC in the blood vessel.

The distal portion38of the DC contains an expandable wire basket assembly58. The wire basket assembly comprises two collars with a plurality of holes. Nosecone54serves as the distal collar, and collar60forms its counterpart at the proximal end. The guidewire tube44traverses freely through the central lumen of the collar60. A plurality of wires62, of material such as nitinol, is positioned between the two collars54and60. The ends of the wires are disposed in the plurality of holes and secured by bonding or other methods known in the art. The nosecone54can be moved closer to the collar60by moving the guidewire tube44in a manner64in the proximal direction. The wires62can deform to create a basket-like structure, generally in a cross-section of a circle. The outside diameter of the wire basket (also referred to herein as a spline) can be varied by changing the distance between the two collars54and60. The hoop strength of the spline structure is determined by the diameter and number of the wires62. The maximum diameter of the deployed wire basket spline is determined by the length of the wires62. The variable diameter spline58is used in the final apposition of the PSG in the AAA. It is also used to hold the PSG in position while removing the purse string filament from the PSG10.

The spline structure may be a braided section of wires of appropriate diameter, length, and number so as to function as a deployable basket. Another way to achieve a basket like structure and function may be to have it constructed from a laser cut tube. The length, width, and thickness of the splines in the laser-cut structure can be optimized to the desired function.

Still referring toFIG. 35A, the multilumen tube40terminates at its distal end at a collar65which has corresponding holes to match the lumens of the tube40. The purpose of this collar65is to provide for a back stop for the PSG10during its deployment in the AAA. A slider tube or outer sheath66forms the outer part of the DC38, and moves slidably over the multilumen tube40. The distal end68of the slider tube66extends over the nosecone54creating an annular pocket70between the slider tube66and the guidewire tube44. The spline58is contained in a collapsed configuration at the distal end of the pocket70. The annular pocket70extends proximally between collars60and65. The PSG10, in its collapsed condition, is housed in this pocket70. The proximal end of the PSG10constitutes loops96(shown inFIG. 36) of the wires33and34. A purse string filament72is weaved through these loops96to capture the PSG10.FIG. 36shows a close up view of the purse string filament72. The purse string filament traverses the length of the DC and resides in the lumen50of multilumen tube40, forming a pair of filaments52.

FIG. 35Bshows the proximal portion74of the delivery catheter DC. Slider tube66terminates in a Tuohy Borst (TB) adapter76. The multilumen tube40passes inside the slider tube66and passes through the TB adapter76. The TB adapter provides a fluid seal78over tube40against a fluid leak from the body lumen to the outside. The tube40itself terminates at another TB adapter80which provides for a fluid-tight seal82around the guide wire tube44passing therethrough. The guidewire tube passes through a hemostatic valve splitter84which provides a fluid seal86against the guidewire tube44. The hemostatic valve splitter84has a side arm88attached to yet another TB adapter90providing a fluid seal92against the purse string pull wire pair52. The pull wire pair52is terminated in a plug94which allows the handling of the pull wires. The guidewire tube44terminates another TB adapter95which provides a fluid seal97against the guidewire46.

FIG. 35Cshows the distal portion38of an alternative embodiment of the delivery catheter system (DC) ofFIG. 35A. The DC ofFIG. 35Cis similar in many aspects to the DC ofFIG. 35A, and comprises many of the same components as described with reference toFIG. 35A. However, instead of an expandable wire basket assembly or spline (58,FIG. 35A) coupled to the nosecone54and the collar60, the distal portion38comprises an expandable balloon59. The expandable balloon may comprise any expandable catheter balloon as known in the art, with suitable dimensions and material strength to form a firm apposition against the inner wall of the aneurysm when expanded. The expandable balloon may be used to hold the PSG in position while removing the purse string filament from the PSG10, and/or during the final apposition of the PSG in the AAA. The delivery catheter system may further comprise an expansion lumen for expanding the balloon.

FIG. 36shows the threading of the pull wire72(as shown inFIG. 35A) through the loops96at the proximal end of the PSG10. As shown, the wire is threaded through the loops96to form a purse string98preferably extending circumferentially all the way around the proximal end of the PSG10, then passing through one or two lumens of the collar65and the tube40becoming a pair52. As the wire pair52is pulled proximally in a manner100, the purse string tightens and collects the loops96in a compact bundle. This bundle can then be pulled proximally in to the slider tube66. In this manner, the PSG10can be pulled inside the slider tube66in its entirety and it resides inside the slider66in a collapsed condition. This allows for multiple attempts of the deployment of the PSG10in the AAA. In the configuration shown inFIG. 36, only one pull wire is used to activate the reloading of the PSG10inside the slider tube66. The pull wire72can be made of a metal, such as nitinol, or a non-metal, such as nylon. The pull wire72can also be made of a bio-degradable material.

FIG. 37shows a purse string pull wire mechanism employing a plurality of pull wires. Each pull wire may be threaded through a subset of the loops96. For example, as shown inFIG. 37, pull wire102is threaded through few of the loops96, and pull wires104and106are threaded through different sets of loops96. These pull wires form their own pairs and can be fed through separate lumens of the tube40. These pull wire pairs108,110, and112exit through the side port88at the proximal end of the delivery catheter terminating in their own individual plugs (plugs not shown). The retraction of the PSG10into the slider66is achieved by pulling the wire pairs proximally. The advantage of the multiple pull wires is that during removal of the pull wires, the wires encounter reduced friction by virtue of being engaged in fewer loops.

The method of deployment of a self-expanding, self-adjusting, and self-orienting PSG in the AAA is described next. As shown inFIG. 38, the distal portion38of delivery catheter (DC) is advanced over a guidewire46in a conventional manner from the femoral artery entrance to the site of the AAA. The DC is advanced until the spline basket58or an expandable balloon (not shown) is positioned in a suprarenal location. The PSG10is contained inside the slider tube66in a collapsed configuration. The delivery catheter may be advanced until the axial position of the prosthesis, along a longitudinal axis of the AAA, is slightly past the axial position of the target delivery region.

Now referring toFIG. 39, the slider tube66is moved proximally in a manner114, from the far end towards the near end of the PSG, to allow the prosthesis to progressively self-expand. The proximal portion of the PSG10is held against collar65which serves a back stop. The distal or far end116of the PSG10is first released and it opens up in a self-deploying, self-adjusting manner as described herein.FIG. 39thus shows the partial deployment of the PSG10in a suprarenal location at the site of the AAA.

FIG. 40shows complete retraction of the slider tube66exposing the PSG10in the AAA space still in a suprarenal location, with the prosthesis positioned superior to its target delivery region. At this location, the shape of the exposed, self-expanded PSG10does not yet line up with the AAA, and the contours of the outer surface of the prosthesis do not axially and/or rotationally align with the contours of the inner wall of the AAA. Consequently, the internal shape of the AAA can place constrains on the PSG at some locations of mismatch between the PSG and the AAA. Constrains placed on the prosthesis by the shape of the target region of delivery can cause the prosthesis to remain in a collapsed or partially collapsed configuration at these locations. For example, at portion118of the body of the PSG, the tendency of the PSG to expand further is constrained by the inner wall of the AAA against which portion118is held. As described in further detail herein, the prosthesis in a collapsed or partially collapsed configuration comprises stored potential energy, urging the collapsed prosthesis to self-orient and self-adjust into a configuration that yields the lowest energy state.

To position and orient the PSG properly in the target delivery region, the prosthesis can be retracted slowly towards the target region, from a far end position to a near end position. The axial movement of the prosthesis towards the target region allows the prosthesis to self-orient by rotating about the longitudinal axis of the AAA into the proper orientation with respect to the AAA. For example, as illustrated inFIG. 40, the PSG10bundle is pulled slowly proximally in a manner120by pulling on the wire pair(s)52in a manner126, towards the target region of delivery. As the PSG bundle moves linearly in the proximal direction along the axis of the vessel, the prosthesis bundle self-rotates in a manner124about the longitudinal axis of the AAA, due to factors described in further detail herein. The prosthesis can translate and self-rotate until the contours of the outer surface of the prosthesis are rotationally aligned with the contours of the inner walls of the AAA. It is important that the blood flow through the aorta not be blocked during the axial movement or retraction of the prosthesis. The incompletely deployed PSG, having pockets of mismatch between the PSG and the AAA, allows the blood to flow around the collapsed or partially collapsed portions.

The impetus for the self-rotation of the PSG comes from the fact there is potential energy stored in the collapsed PSG10. The potential energy is made of two components. One portion is the radial compressional energy which is stored in the wire filaments33and34by virtue of their deformation as they are held in a constrained or collapsed configuration inside the slider tube66. The second component, namely, the torsional or rotational potential energy is stored in the twisted structure of the PSG10bundle. This rotational potential energy is created by virtue of the fact that as the PSG10is being loaded inside the slider tube66, the PSG10bundle is forced to rotate due to the direction of the wire twists, as described in further detail herein, such that the collapsed PSG bundle is stored in a twisted configuration. These two forms of potential energy are released during deployment of the PSG10. PSG10finally takes a form of the lowest energy state, namely, a free state of deployed shape. However, in the situation when the PSG10is constrained in a suprarenal location, it is not yet able to release all the torsional (or rotational) potential energy. The torsional energy is released by self-rotation124of the PSG bundle. The tendency to self-rotate to a free shape encounters a friction between the surface24of the PSG10and the inner wall128of the blood flow lumen. When the PSG10is in a stationary state, the friction is termed ‘static’ friction and may be sufficiently high to prevent the PSG from self-rotating. However, as the PSG10is put into a slight axial motion120, the surfaces24and128now are in ‘kinetic’ friction, which is much lower than the static friction. Therefore, the rotational forces are able to overcome the kinetic friction, resulting in a freer self-rotation of the PSG to achieve rotational alignment with the contours of the target delivery region.

The direction of the self-rotational motion is determined, in part, by the direction of the wire twists comprising the PSG10. Referring toFIG. 12G, a PSG composed of substantially all the twists35in the clockwise (cw) direction will have a tendency to rotate in a clockwise direction as viewed from the inferior to superior direction. Conversely, as shown inFIG. 12H, a PSG composed of substantially all the twists35in the counterclockwise (ccw) direction will have a tendency to rotate in a counterclockwise direction as viewed from the inferior to superior direction. A PSG10composed of random twist patterns35will not have a preferential direction of rotation. Therefore, a prosthesis may be biased to twist in a pre-determined direction upon self-orientation, by constructing the prosthesis using a wire frame having a specific pattern or direction of wire twists, such that the direction of rotational motion of the prosthesis during its self-orientation in deployment can be controlled. The prosthesis can be constructed to rotate in one direction during self-orientation, or the prosthesis can be constructed to have a plurality of regions each configured to have its own rotational bias during self-orientation. For example, a first region of the prosthesis can be biased to twist in a first direction, while a second region can be biased to twist in a second direction opposite the first direction.

The tendency for a favored direction of rotation based on the direction of the wire twists35(cw or ccw) can be minutely explained in the following manner. As the PSG10bundle moves proximally in a manner120, the interface between the twisted wire surface and lumen surface occurs at an angle whose direction is determined by the direction of the twist. During motion120, in relative terms, the lumen surface is moving superiorly against wire twist(s). This motion imparts a sideways force on the wire of the twist as it presents itself at an angle (of the twist) to the luminal surface. This sideways force has a torsional vector component which results in a rotational movement of the PSG bundle10. The same force vector comes in play when the PSG10is being loaded into slider66by pulling the PSG10in a linear fashion proximally.

Thus, as the PSG bundle10is being moved proximally along the axis of the lumen during deployment, the bundle also self-rotates, wherein the direction of the rotation is determined by the twist direction (cw or ccw) of the wire frame of the PSG. The intended result is the release of the torsional potential energy. The preferred direction of the rotation can be predetermined by examining the anatomy of the AAA, and the tendency of the lay and angle of the PSG in the collapsed or partially collapsed configuration as it is positioned in the location suprarenal to the AAA. This angle of the collapsed or partially collapsed PSG can help guide the direction of the required twist pattern with which the PSG is fabricated.

The twist pattern35can thus be configured to facilitate the self-rotation124of the PSG bundle during the deployment of the PSG, such that its torsional potential energy is released in the most efficient manner. The linear or axial motion120of the PSG in the inferior direction puts the bundle in a kinetic friction state allowing for an easier self-rotation of the PSG bundle.

The PSG10can be constructed in a manner such that its superior end is in line with an anatomical feature, such as the edge of a vertebra, when deployed in its target axial position. The superior edge of the PSG10may be disposed with radio-opaque markers25which are visible under fluoro x-ray guidance. Continuing with the movement of the PSG10inferiorly, the PSG10comes to a position where its superior end matches the target anatomical location (such as the edge of a vertebra) when viewed under fluoro guidance. At this point, substantially all the stored potential energy is released and the PSG10can take a self-oriented, rotationally conformal position against the AAA. In the rotationally aligned position, not only do the contours of the outer surface of the PSG align with the contours of the inner wall of the aneurysm, but also the lateral apertures or fenestrations18and20of the PSG align with the corresponding ostia of the renal arteries RA. As described herein, the locations of the RA may be determined based on one or more images of the aneurysm and the prosthesis may be manufactured to comprise lateral apertures configured to align with the ostia of the RA when implanted. Therefore, the self-orientation of the prosthesis to rotationally align with the contours of the aneurysm automatically results in the alignment of the lateral apertures with their corresponding ostia. In this way, the self-orienting prosthesis not only ensures complete conformation with the geometry of the aneurysm, but also facilitates the alignment of one or more lateral apertures of the prosthesis with their intended targets. By contrast, a conventional stent graft with no self-orienting capability or particular rotational orientation would require manual orientation to align the later apertures with their corresponding ostia.

Thus, the PSG is aided in self-aligning or self-orienting itself rotationally within the AAA pocket by (a) twist pattern (direction) of the wires of PSG10and (b) axial or linear motion of the PSG which puts the PSG in a kinetic friction mode, facilitating the rotational motion of the PSG. Helped by the aforementioned factors, the PSG can come to its lowest energy state by aligning itself conformally against the AAA.

While the PSG is herein described to be manually pulled or retracted axially along the lumen and towards the target deployment region, the axial movement of the PSG may also comprise a self-translation component. As described herein, the PSG self-orients rotationally as it is being retracted towards the intended final position, in order to reach the lowest energy state wherein the contours of the outer surface of the prosthesis substantially match the contours of the target region. As the PSG moves closer to its target axial position, the tendency of the PSG to rotate into its final orientation can cause axial self-translation of the PSG into the proper axial position, driven by the self-rotation of the PSG. Therefore, the PSG is not only translated manually, but in at least some stages of its placement into its target axial position, the PSG may self-translate axially along the lumen such that the contours of the outer surface of the prosthesis axially align with the contours of the target region.

Once the PSG reaches its proper axial position and rotational orientation with respect to the AAA, the prosthesis can self-adjust in one or more locations along its body to accommodate the exact shape and dimensions of the AAA, as described herein. For example, the PSG can be manufactured to be slightly oversized with respect to the shape of the AAA as determined from a CT scan, and constructed with self-adjustable wire frame construction as described herein (e.g., 41 or 31 configurations with 3-2-2-2 or 3-2-2 twist loop configurations). When the PSG is placed in the proper axial position and rotational orientation, the twist loops of the wire frame can open up appropriately to adjust the shape and dimensions of the frame at any locations of mismatch between the prosthesis and the AAA, to match the internal geometry of the AAA. For example, at locations of mismatch wherein the diameter of the PSG in its fully-expanded configuration is larger than the diameter of the AAA, the PSG may self-adjust to reduce its diameter to match the diameter of the AAA.

FIG. 41shows the PSG10deployed in the AAA space. The proximal end of the PSG is still held together by the purse string72. The spline58(or the expandable balloon) remains in place supra-renally. If it is determined that another attempt is needed in placing the PSG, the PSG can be retracted back inside the slider tube66in a manner described inFIG. 40. Another attempt can then be made, as described above, to deploy the PSG10in the AAA. The goodness of the PSG placement in the AAA can be determined by comparing the before and after fluoro images of the AAA space. The fenestrations18and20of the PSG should be aligned with the ostia of the renal arteries RA. In addition, the flow of the contrast fluid can be observed, it should show that the contrast flow into the side branches SB is absent or largely diminished, unless the PSG comprises additional lateral apertures to accommodate the side branches.

Optionally, the PSG may be rotated manually about its longitudinal axis at any stage of the deployment, to facilitate the self-orientation of the PSG into its target rotational orientation and to ensure that the PSG is finally oriented into its proper rotational orientation.

Once it is deemed that the PSG has been correctly implanted in the AAA, the pull wire string is preferably removed using the following method. Referring toFIG. 42, the spline assembly58is moved proximally such that the spline wires62are slightly superior to the proximal end of the PSG10. The spline is deployed by pulling the nose cone54towards the collar60by moving the guidewire tube44in a manner130. As the nosecone54moves closer to the collar60, the wires62of the spline expand outwards in a manner132to form a basket. The basket continues to be expanded until the wire elements62are firmly against the inner surface128of the PSG10. This position of the distended spline holds the PSG10in place to guard against any movement as the purse string wire is withdrawn. One of the filaments of pair52is pulled proximally in a manner134. This causes the other end of the wire to move in a manner136. The wire pulling motion is continued until the wires clears through the wire loops96. Once the wire72is removed from the PSG10, the proximal end138is released and the PSG self-deploys in its intended place in the AAA Similarly, for the case where multiple pull wires used (as shown inFIG. 37), each wire can be pulled out in the same manner as described above for the single wire pull string.

The final apposition of the PSG in the AAA is achieved by use of the spline assembly as shown inFIG. 43. The spline wires are deployed (as described above) from superior to the inferior locations. By way of example, the spline is deployed in the superior location140to further apposition or “tack” the PSG against the wall of the AAA. Similarly, the spline is shown deployed in an inferior location142. The spline can be deployed in as many locations in any order as deemed necessary. The use of the spline for this purpose is advantageous as the open structure of the spline allows the flow of blood therethrough during the apposition process.

In embodiments of the delivery catheter system comprising an expandable balloon assembly (59,FIG. 35C) in the place of the wire basket or spline assembly58, the expandable balloon may be used to facilitate the removal of the pull wire strings and the final apposition of the PSG in the AAA. The expandable balloon may be expanded to firmly engage the inner surface of the PSG while the pull wire strings are removed, thereby preventing axial movement or dislodging of the PSG from the target site. The expandable balloon may also be expanded at one or more locations along the PSG to tack the PSG against the wall of the AAA.

Finally, the delivery catheter is removed from the patient and the entry site at the femoral artery is sealed in a conventional manner. The PSG10is now implanted in the AAA as shown inFIG. 3B.

In any of the embodiments described herein, the filament may be any combination of wires having any cross-section such as round, square, rectangular, etc. and the size of the wire may be adjusted in order to various properties of the prosthesis such as its profile in the collapsed configuration, its stiffness and strength, and other properties. In preferred embodiments, a round nitinol wire is used having a diameter of 0.005 inches to 0.008 inches. Exemplary wire diameters of 0.005 inches, 0.0055 inches, 0.006. 0.0065, 0.007, 0.008 inches may be used.

Additionally, any of the prostheses may carry a therapeutic agent such as an antithrombotic agent, antibiotic, etc. for localized and controlled elution at the treatment site. One of skill in the art will also appreciate that the prosthesis described herein preferably has a mesh with a polymer or fabric cover disposed thereover, but the prosthesis could be a mesh only (without the membrane) to support the damaged or diseased tissue, or the prosthesis could be the polymer or fabric cover only. Thus, the fabrication methods and delivery methods described herein apply to either embodiment of prosthesis.