Antifouling stent

Abstract

An in-vivo prosthesis device (600) comprising a tubular structure having an outer surface and an inner surface such that the inner surface positions the lumen, wherein the outer surface comprises a microstructural pattern having a hierarchical microstructure that produces an adhesion effect to a target surface. The inner surface comprises a superhydrophobic or oleophobic microstructural pattern that can be antifouling, and the microstructural pattern of the inner surface comprises microridges. Further, the outer surface may comprise pores that fluidly connect the outer surface to the inner surface for transporting fluid from the target surface interface into the in-vivo prosthesis lumen.

Description

Technical Field

[0001] The present invention relates to a gastrointestinal stent.

[0002] Stents are frequently used to expand, dilate, or maintain the patency of a narrowed body cavity. The stent may be positioned across the stenotic region while the stent is in a compressed state. The stent can then be expanded to widen the lumen. Stents used in the digestive system are generally composed of plastic or a coated metal wire. Plastic and coated metal wire stents facilitate the retrieval and / or replacement of the stent during follow-up procedures.

[0003] However, plastic stents are not expandable like metal wire stents. That is, plastic stents have a fixed diameter. Since plastic stents are often delivered through the working channel of an endoscope, the diameter of the working channel limits the diameter of the stent. For example, plastic stents typically have a diameter of 11.5 Fr (French catheter scale) or less. However, such small-diameter stents tend to rapidly clog within the bile duct and pancreatic duct, thereby requiring replacement every three months or even sooner.

[0004] In the case of coated metal wire stents, since such stents can be compressed and then expanded at the delivery site, there are few limitations on the diameter of the stent when deployed. However, like plastic stents, these stents can have problems with movement from their target lumen site and leakage of fluid around the outer surface of the stent. In some instances, fluid accumulation between the outer surface of the stent and the target lumen surface can cause stent movement, although there are other causes for movement. An apparatus that can prevent fluid accumulation between the stent and the target lumen surface can resist stent movement due to fluid accumulation.

Background Art

[0005] Conventional stents are designed to secure a drainage stent at a transplant site within a body cavity, including some mechanical mechanism for holding the drainage stent within the body cavity. For example, retention flaps that project radially from a tubular body have been previously used. The retention flaps may be formed by creating diagonal slits along the length of the tubular member. Each slit defines a tab that allows the tab to project outside the outer surface of the tube and engage the luminal surface of the bile duct to prevent movement. The tabs at the ends on both sides of the drainage stent typically extend toward the center of the stent and radially outward. The openings defined by the tab-forming skips can provide access to the interior of the stent, in which case cells or other materials may tend to develop into obstructions that cause restrictions in the flow through the stent.

[0006] Drainage stents in the prior art also included one or more curled or coiled ends. For example, the distal end and / or proximal end of the drainage stent may have a curled configuration often referred to as a "pigtail" configuration. One such example is shown in U.S. Patent No. 5,052,998 to Zimmon. This document discloses a retention drainage stent having a flap at one end, a series of drainage perforations along the length of the drainage stent, and a pigtail configuration at the opposite end. Other stents include fixed flaps or pigtail loops at both ends of the stent. Conventional stents are provided with both those having drainage perforations and those without, as shown in the Zimmon patent.

[0007] Other structures, such as a helical tubular drainage stent having an expandable portion, are disclosed by Rucker in U.S. Patent Application Publication No. 2006 / 0167538, filed on December 21, 2005. Kolb describes a drainage stent having one or more curled portions and a drainage channel having a laterally open portion in U.S. Patent Application Publication No. 2006 / 0052879, filed on August 16, 2005. As is apparent from the foregoing prior art, the geometry of the stent is dramatically affected by the need to fix the stent within the body cavity. Therefore, it is necessary to decouple the fixing mechanism from the stent geometry of the gastrointestinal stent so that the stent can be designed into a more advantageous and effective geometry.

[0008] Furthermore, the insertion of a drainage stent placed by endoscopic sphincterotomy may require stretching and cutting of the sphincter of Oddi and the surrounding area, which may impair the function of the sphincter of Oddi after the insertion of the drainage stent. In addition to the sphincterotomy procedure for inserting the drainage stent, the placement of the position of the bile duct stent at the papilla of Vater (e.g., across the sphincter of Oddi) can also result in duodenogastric reflux. The damaged sphincter of Oddi allows reverse fluid flow from the duodenum, or duodenogastric reflux, causing the deposition of bacteria and biofilms and, in some cases, occluding the bile duct or drainage stent. Therefore, there is a need for a gastrointestinal stent that does not require stretching or cutting of the sphincter of Oddi and its surrounding area.

[0009] Particularly with respect to bile duct stents, a drainage device can be implanted to treat various conditions. For example, to treat obstructive jaundice, a drainage stent configured as a bile duct stent can be implanted into the biliary tract. FIG. 1 identifies the right hepatic duct that joins the left hepatic duct to form the common hepatic duct, further identifies the gallbladder and cystic duct, the pancreas and the main pancreatic duct, all of the foregoing ducts connecting to form the common bile duct and leading to the duodenum through the ampulla of Vater and the sphincter of Oddi, showing a typical biliary system.

[0010] FIG. 2 illustrates a typical stent placement in the biliary tract system 200. The stent 201 can be placed in the digestive tract near the common hepatic duct 206 and the common bile duct 216 that enter the duodenum 218.

[0011] As a surgical treatment for treating stenosis or occlusion of the biliary tract, a biliary stent placement procedure is known in which a radially expandable biliary stent is implanted in the diseased part of the duct. By performing biliary stent placement, the patency of the diseased part in the biliary tract can be ensured, and as a result, for example, improvement of obstructive jaundice symptoms can be achieved.

[0012] Conventionally, a biliary stent used in the biliary stent placement procedure has a tubular stent body configured to be expandable and a membrane extending in a cylindrical shape protruding from one end of the stent body. The conventional biliary stent is configured such that the membrane extends toward the duodenum when implanted in the diseased part of the biliary tract. The membrane is configured to allow the outflow of bile from the gallbladder to be directed toward the duodenum and to prevent backflow from the duodenum to the gallbladder. In this configuration, the function of flowing the bile flowing out from the gallbladder toward the duodenum and preventing backflow from the duodenum to the gallbladder is called the "valve function".

[0013] Problems caused by tube occlusion and blockage are specific to the biliary tract system because the harsh environment of the biliary drainage system caused by enzymes in the pancreas and biliary tract, as well as microorganisms such as fungi and bacteria that inhabit the tube, are susceptible to complete occlusion by biofilms and organic masses, causing stasis and damage to these tubes. Therefore, in order to minimize or eliminate complications caused by occlusion of the stent lumen, there is a need for a biliary stent having an inner lumen coating that prevents occlusion by these biofilms and organic masses.

[0014] Furthermore, bleeding from the duct can lead to blood clot formation and occlusion within and around the stent, regardless of whether it is due to stent placement or some other cause. Occlusion of the duct due to infiltration by a tumor within the duct wall and external compression by a tumor mass can be a common cause of complications. Therefore, there is a need for a bile duct stent that can have a rigid expanded diameter without requiring a high vertical force applied to the body cavity.

[0015] The treatment of duct occlusion has been partially addressed by stainless steel stents, cobalt chromium stents, inexpensive plastic stents, and more recently, shape memory alloy stents. However, these stents are placed in a harsh enzymatic environment, so occlusion and restenosis occur frequently.

[0016] It is desirable to place a tubular implant, such as a stent, at the point where the bile duct enters the duodenum. This particular opening widens as the bile duct approaches the duodenum. As a result, the desired shape of the implant is frustoconical, but such an implant has a tendency to move inherently due to the non-uniform shape of the stent. Therefore, there is a need for a bile duct stent with a frustoconical profile that also prevents stent movement.

[0017] On the other hand, for applications such as treating benign disorders, for example, a removable stent is desirable. Some uses of stents include their use as a bridge to treatment and a reduction in palliative measures, in part for the improvement of some cancer treatments and other methods of treating malignant growths. However, efforts to improve removability have conflicted with at least some measures taken to reduce the risk of stent movement. There is a need for an improved stent that reduces trauma during stent removal and improves stent adhesion to the body cavity.

[0018] Accordingly, what is needed is, for example, an improved stent having improved resistance to migration, improved stent adhesion to the luminal wall, and / or improved removability while further preventing common problems that occur with prior art devices. Surface textures on stents are not used in the gastrointestinal tract due to problems in highly lubricated environments that cause stent migration. However, the surface textures of the present disclosure employ unique surface microstructures that utilize the lubrication mode of the gastrointestinal lumen to achieve stent fixation. In some embodiments, the surface texture can be configured to create a Wenzel-Cassie zone at the interface between the stent and the body cavity. SUMMARY OF THE INVENTION

[0019] The present disclosure provides an implantable prosthesis that can include a polymeric coating. In some embodiments, the implantable prosthesis can include some surface features such as protrusions or textures arranged in a micro-pattern. As used herein, a micro-pattern can include a regular or irregular array of micro-scale features (e.g., protrusions such as micropillars, voids such as textures). These micro-patterns can be arranged hierarchically on the device.

[0020] The hierarchical structure can include microstructures having a multi-scale form. Recent advances in nanomaterial science have made it increasingly possible to design hierarchical surfaces with specific tunable properties. Most of this research has focused on hierarchical single-layer carbon nanotube films realized by a simple, rapid, reproducible, and inexpensive filtration process from aqueous dispersions. By varying the thickness of the carbon nanotube random network using this filtration process, it is possible to adjust the wettability of the microstructure based on capillary action. This effect can also be applied to porous films.

[0021] It has also been discovered that a multifractal structure can generate a unique two-dimensional extension of the Wenzel and Cassie-Baxter theories of surface wetting, especially when constructed in a hierarchical surface morphology. Capillary phenomena in the hierarchical morphology of the film can generate surprising adhesion properties. For example, the Applicants have calculated that the difference in surface energy between the microstructured surface and the wetting target, when considered separately and when in contact, can increase in proportion to the number and size of the juxtaposed hydrophilic and hydrophobic regions on the microstructured surface and the target surface. The greater the difference in surface energy between the liquid free surface and the solid contact surface, the more it can provide a quantitative measure of adhesion. This difference in surface energy is called the barrier energy, or the energy required to break the interface with this structure and enable translation.

[0022] The long-range ordering of water can be protected from thermal disruption by the establishment of Wenzel-Cassie zones of hydrophilic regions bounded by hydrophilic-hydrophobic boundaries. Furthermore, the hydrophobic regions can function as a reservoir primed for displaced hydrophobic solutes, further strengthening the structure and increasing the barrier energy. This effect can be particularly enhanced when the target surface is biological tissue, since the fluid at the interface between the microstructured surface and biological tissue is generally a suspension of lipids (hydrophobic) in water (hydrophilic).

[0023] In some embodiments, there can be a hierarchy of ordering, from microscopic zones of water and lipids to the exclusion of lipid particles of multi-molecular size, the ordering of individual water molecules, and so on. Thus, it is reasonably expected that a microstructured surface, which is similarly hierarchical and ordered at least at a two-dimensional scale, enhances the localization effect that generates a high barrier energy.

[0024] The present disclosure may include an apparatus that presents an anti-fouling surface that utilizes a liquid interface between an in-vivo prosthesis, such as a stent, and a target surface, i.e., a lumen of tissue, to 1) immobilize the in-vivo prosthesis on the target surface, 2) form a fluid seal between the in-vivo prosthesis and the target surface, and / or 3) either a) resist deposition in a solid state on the in-vivo prosthesis surface or b) promote deposition that oozes in a substantially unstable, predictable, and intentional manner.

[0025] The fixation, sealing, and anti-fouling functions of the apparatus disclosed herein may result from modification of the surface energy of the disclosed surfaces. Hydrophilic-hydrophobic interfaces, such as those developed in the Wenzel-Cassie interfacial state, can play a more profound role than generally assumed in the prior art. Solutes in an aqueous suspension are excluded over a wide range from near many interfaces, and such exclusion results from long-range confinement of water molecules, nucleation at the interface of macrostructured surfaces, and favorable protrusion into the aqueous phase, similar to what occurs in liquid crystals. The presence of such unexpectedly large zones of mobility-restricted water can affect many features of surface and interfacial chemistry.

[0026] The present disclosure further relates to an apparatus including an adhesive surface that supports a microstructured surface, the microstructured surface including at least two types of features. Further, the aforementioned adhesive surface may include features where the lateral aspect ratio of the features ranges from about 0.1 to about 50 for each feature and at least one feature dimension varies with a coefficient of at least 10%. For example, in one embodiment, there may be two sets of pillars, one set having a diameter of 5 microns and a height of 30 microns, the other set of pillars having a diameter of at least 15 microns and a height of 75 microns, and the first set of pillars being disposed on the upper surface of the second set of pillars. At least two of the feature dimensions (height, width, and / or length) may be microscopic. In some embodiments, all three of the feature dimensions (height, width, length) may be microscopic.

[0027] In at least one embodiment, the intravascular prosthesis can optionally have an expanded state and a contracted state and, in some cases, can include a stent having a polymeric coating (e.g., by adhesion, etc.) attached to the outer surface of the stent. The stent may have an inner surface that defines a lumen. The stent can have an outer surface and a stent thickness defined between the inner surface and the outer surface. The stent can include a plurality of surface textures extending from the stent surface, and the textures are arranged in a micro-pattern. The micro-pattern may be present on the outer surface and / or the inner surface, or both. The micro-pattern on the outer surface can fix and / or seal the stent to the target surface. The micro-pattern on the inner surface can withstand fouling. In at least one embodiment, the stent may be a flare stent. Optionally, the stent can include surface features for performing fluid transport in which fluid is directed from the space between the outer prosthesis surface and the target lumen surface, or fluid transport means by which fluid can be transported into the lumen of the stent. The fluid transport means can be achieved using through-holes that can generate a flow gradient by capillary action. In some embodiments, the through-holes may have a uniform passage such as a cylinder. In some embodiments, the through-holes may be tapered or frustoconical.

[0028] In one or more embodiments, the stent may include a base and a tissue engagement portion. The base can include a first surface (e.g., attached to or comprising the outer surface of the stent). The tissue engagement portion may include a second surface facing outwardly from the stent. The tissue engagement portion can include a structure defining a plurality of protrusions or wells extending outwardly / inwardly from the second surface away from / toward the base. In at least one embodiment, the surface texture may be arranged in a micropattern. In one or more embodiments, the base and the stent may share a boundary line. In one or more embodiments, the base may cover any aperture of the stent. When the in-vivo prosthesis is expanded or in an implanted configuration within a lumen defined by a blood vessel wall, the structure defining the plurality of surface textures can generate an adhesive force capable of creating an interlock between the blood vessel wall and the in-vivo prosthesis. The interlock may be a fixation and / or a fluid seal.

[0029] In one or more embodiments, the stent surface can include a plurality of protrusions (e.g., micropillars) of at least two scale dimensions extending hierarchically from a base (e.g., outwardly from the stent). In one or more embodiments, the protrusions may be arranged in a regular micropattern (e.g., of the micropillars). The external surface microstructure can be capable of 1) generating an axially directed shear force to inhibit axial movement of the stent, or 2) generating a radially directed perpendicular force to attract a target lumen surface to the external stent surface to create a sealing means, or both.

[0030] In one or more embodiments, the fixation and sealing capabilities can introduce the locking ability to the target surface of the device, either together or individually, and the external microstructure of the device changes dimensions by fluid absorption when placed in the target lumen, and this fluid absorption changes the dimensions of the microstructure and creates a gripping action. For example, the microstructure pillars can expand to capture tissue placed in the gaps between the pillars.

[0031] In one or more embodiments, the stent surface may include a plurality of fluid-conductive microstructures designed to transport liquid in a desired direction. Typically, the fluid can be transported axially along the outer surface of the stent to remove fluid from the space between the outer surface of the stent and the target surface. Alternatively, the fluid may be transported radially through the holes in the stent wall from the interfacial volume to the lumen of the stent. The latter fluid transport feature may be used in bile duct stents because such stents often cross tissue lumen branches and it is desirable for the intersecting lumens to be drained into the lumen of the stent.

[0032] In one or more embodiments, the stent surface can effectively provide an anti-fouling surface that can prevent the accumulation of fluid components conducted through the lumen of the stent, and may include a plurality of protrusions of at least one scale dimension extending inwardly from the base towards the lumen of the stent.

[0033] In one or more embodiments, the stent surface can include a plurality of protrusions of at least one scale dimension extending inwardly from the base towards the lumen of the stent that can provide a surface that promotes the deposition of a particular morphological type. For example, the microstructure may be arranged as circular islands that can promote a discontinuous deposition that easily falls off as particles.

[0034] Alternatively, an absorbent surface coating on the microstructure can result in roughening of the deposited layer.

[0035] While not desiring to be bound by theory, the target tissue may engage with the micro-patterned surface or coating via one or more non-mechanical mechanisms. As disclosed herein, in certain embodiments of the present disclosure, non-abrasive engagement can be achieved by creating one or more interfacial structures such as, but not limited to, 1) Wenzel-Cassie, 2) capillary, and / or 3) eigenmode or Schallamach.

[0036] In some embodiments, the target tissue can interlock with a micro-patterned coating having one or more microstructures by tissue invasion around and / or between one or more micro-pillars. In at least one embodiment, the tissue gripping mechanism can effect tissue engagement and / or interlock with a micro-patterned coating having one or more textures (e.g., voids, negative spaces, etc.) or structures defining a network of connected textures, and tissue and / or intracellular colonization occurs within the texture.

[0037] In one or more embodiments, a van der Waals binding mechanism can form between tissues in contact with a micro-patterned coating that can include, for example, a mucoadhesive gel.

[0038] In one or more embodiments, the engagement of the tissue with a micro-pattern having an appropriate geometry can be due to the proximity attraction by van der Waals forces. As used herein, "interlock" can be understood to refer to the engagement of the target tissue by a microstructure having micro-pillars and / or micro-holes via any one or more of the mechanisms described herein or otherwise known to those of ordinary skill in the art (e.g., tissue colonization, chemical bonding, proximity attraction, etc.).

[0039] However, some embodiments of the present disclosure may not rely on tissue engagement by grasping or friction. In fact, the initial tissue engagement mechanism may enable localization of tissue to the device by the surface energy characteristics of the microstructures herein. Surface energy interactions mediated by capillary bridges may characteristically be non-destructively reversible, such that the stent can be removed from the body cavity without damaging the luminal tissue.

[0040] The Applicants have surprisingly found that a surface structure comprising hydrophilic and hydrophobic domains juxtaposed either laterally or in a laminated fashion can attract or repel different intracellular antibody fluid and solid components. For example, the hydrophilic regions of the surface texture may be associated with hydrophilic tissue components, and the hydrophobic regions of the surface texture may be associated with hydrophobic components. During this association, the interfacial energy decreases and can result in stent-tissue adhesion. Disruption of this adhesion state may require energy consumption, and thus, the Wenzel-Cassie association may be stable against dislocation. Even if a microdislocation occurs, the Wenzel-Cassie state can be rapidly re-established.

[0041] In certain embodiments, van der Waals forces may be involved in the formation of the Wenzel-Cassie adhesion zone, but it is understood that they do not result in protein denaturation and can be understood to characterize the normal binding mechanisms disclosed herein. In the Wenzel-Cassie interaction zone, the hydrophilic and hydrophobic zones may interlock, and stent displacement may require mixing these zones, which may require energy input.

[0042] In a second unexpected aspect, Applicants have discovered that capillary action can play a role in the stabilization of the Wenzel-Cassie regime and the provision of an initial mechanical aspect that can draw the stent and the lumen surface together. For example, wells or through-holes disposed on the stent surface can employ the surface tension difference between hydrophilic and hydrophobic domains, as well as the surface energy of the substrate, to transport liquid during the formation of the stent-lumen interface. For example, when the lumen surface is eluting liquid, the surface texture of the stent can be configured to induce a capillary domain that pulls this fluid away from the stent-lumen interface.

[0043] It should be understood that hydrophilic / hydrophobic states can be induced on a surface 1) chemically or based on molecular structure and / or 2) texturally, and can be induced by the geometric shape and hierarchical arrangement of the microstructure. The hydrophobicity of both surface types can typically be characterized by surface energy.

[0044] Finally, Applicants have discovered that the target surface can exhibit a characteristic spatial frequency response. This property of the material is sometimes referred to as the surface's eigenmode response. In the context of the present disclosure, the eigenmode response can be the induction of surface wrinkles at a target surface having a characteristic spatial frequency. By matching the spatial frequency of the textured surface of the stent to the eigenmode of the lumen surface, the adhesive interface can be substantially stabilized. In particular, matching the spatial frequency of the textured surface over several spatial eigenmode frequencies of the target surface by the hierarchical arrangement of the surface texture can result in a number of interfacial zones that form an energy minimum zone. Disrupting these energy minima requires energy, and thus the stent can be stabilized against movement without undesirable forces acting on the tissue surface (e.g., those causing inflammation, cell death, or cell injury).

[0045] It is to be understood that the Wenzel-Cassie interface can be considered a multi-dimensional low-energy state juxtaposing attractive and repulsive forces. The surface domains can be attractive and / or repulsive due to various factors. These factors can include, but are not limited to, the ion content of the interfacial layer, the degree of order or disorder of the material including the surface pattern, and various chemical treatments of the surface. Thus, as used herein, the Wenzel-Cassie interface can include any interface where an attractive domain and a repulsive domain are formed between a textured surface and a target surface in a low-energy state. The difference between the interfacial energy state and the energy states of the separating textured surface and target surface can be linearly proportional to the shear adhesion strength. To achieve a high peel force (vertical force adhesion), a capillary mode can be adopted in the surface pattern design.

[0046] As disclosed herein, the combination of the above discoveries can result in an adhesive textured surface that can be optimized for various target surfaces. Those experienced in the technical field of solid-state physics can measure the energy difference between the separated and bonded states of the textured surface and the target surface to consider how to design the specific surfaces disclosed herein.

[0047] In addition to any adhesive properties of the devices disclosed herein, a repulsive surface may also be required to prevent fouling of the stent after deployment into the tissue lumen. Such a surface can use an overall hydrophobic surface or a zoned hydrophobic surface, and the alternating zones of hydrophobicity and hydrophilicity can prevent biofilm formation and / or the movement of fungi or bacteria. In one embodiment, the inner stent surface may be a regulated hydrophobic / hydrophobic surface, and the outer surface may be a regulated hydrophobic / hydrophilic surface, and each surface can be described as a hierarchically patterned surface designed for a specific biological interface.

[0048] The micropattern may be specially designed for a particular tissue in order to effectively localize the stent to the target tissue. In at least one embodiment, the micropattern may be present along at least a portion of the intravascular prosthesis. In at least one embodiment, the texture of the micropattern may be uniform, or the micropattern may be formed from a texture having a first configuration and a texture having a second configuration.

[0049] The shape of at least a portion of the plurality of textures can be selected from the group including cylinders, rectangular prisms, polygonal prisms, spheres, spheroids, ellipsoids, and similar shapes. Some textures are continuous and can be selected from the group including sinusoidal height variations (waves), ridges, concentric structures, and similar shapes.

[0050] In at least one embodiment, the texture of the micropattern may be at least two types of cylindrical pillars, each cylindrical pillar having a diameter and a height, and the diameter of each cylindrical pillar may be equal to 0.1 to 1 times its height. The pillars may be hierarchically stacked, arranged in an offset rectangular grid pattern, and arranged on a substrate that varies sinusoidally.

[0051] In at least one embodiment, each texture of the micropattern has a first dimension and a second dimension. The first dimension may be about 1 micron to 1000 microns (e.g., about 1 micron to 100 microns), and the second dimension may be about 1 micron to 1000 microns (e.g., between about 10 microns and 150 microns). One texture may be completely disposed on top of another texture, and the ratio of the pitch of the first texture to the pitch of the second texture may be about 0.1 to 0.5. In at least one embodiment, each protrusion has a ratio of the first dimension to the second dimension that may be about 0.2 to 0.3.

[0052] In at least one embodiment, the intravascular prosthesis may be retrievable, for example, by a retrieval loop at the distal end of the stent.

[0053] In at least one embodiment, the endoprosthesis may be distally fixed by one or more pigtail configurations of the stent.

[0054] Some methods of manufacturing embodiments of the endoprosthesis are known in the art. One manufacturing method includes forming a polymer coating, the polymer coating including a base and a tissue engaging portion. The base includes a first surface. The tissue engaging portion includes a second surface facing outwardly from the first surface and a structure defining a plurality of textures extending inwardly or outwardly from the second surface toward the base. In one or more embodiments, the textures are arranged in a micropattern. The method further includes providing a stent having an inner surface and an outer surface defining a lumen and attaching the base of the polymer coating to the outer surface of the stent, the inner surface of the stent, or both.

[0055] In one or more embodiments, the micropattern of the texture is created using lithography techniques, salt leaching, electrospinning, and / or laser ablation. This can be done. In some embodiments including a micropattern of micropillars, the polymer coating can be formed by injecting a polymer material into a mold having a reverse of the micropattern and, optionally, applying temperature or pressure to the mold using soft lithography techniques or by etching the polymer coating from a layer of the polymer material, either before the polymer material cures. In at least one embodiment, an adhesive layer is applied to at least one of the surface and the outer surface of the base of the stent. In at least one embodiment, the polymer coating is formed as a tubular structure. In one or more embodiments, the polymer coating is formed as a strip that is wrapped around the outer surface of the stent (e.g., wound helically, circumferentially, randomly, etc.).

[0056] In at least one or more embodiments, the polymeric coating is disposed on the stent such that a portion of the stent is enabled to move relative to the target tissue. This feature is particularly important when the target lumen generates peristaltic motion. An appropriate combination of "slip" and "stick" characteristics at an appropriate spatial frequency can enable the stent to transmit peristaltic motion without being displaced by such movement. For example, a circumferential ring of a textured surface may be disposed on the stent at a spatial frequency that is a major portion of the peristaltic spatial frequency. For example, if the spatial frequency of the peristaltic motion is 1, the ring can be disposed at 1 / 3 of that spatial frequency. Alternatively, one end of the stent may have no surface texture and the other end may have a surface texture, such that the compressive pressure between the two ends is canceled out by the slippage of one end.

[0057] The present disclosure can include embodiments that include a textured surface stent device, which provides sufficient fixation while reducing the risk of movement and reducing fluid accumulation between the external stent surface and the target lumen, and further provides an internal microstructured surface that suppresses fouling of the surface.

[0058] The present disclosure can include embodiments that include a stent that is adapted to both resist movement within a body cavity and conform to a tortuous delivery path or delivery location. The stent can include a first section that is adapted to be adapted to the shape of the body cavity through which this section passes when being transported, or the shape of the body cavity that surrounds this section when being deployed, of a predetermined compressibility, typically self-expanding. The stent can also include a second section that can move freely within the target lumen.

[0059] The endoluminal stent graft may include one or more segments of a healing promoter attached within the proximal fixation region of the endoluminal stent graft and optionally within one or more distal fixation regions. The healing promoter can be a chemical substance disposed in an absorbent layer or simply a second textured surface designed to induce intracellular proliferation of a particular type. The healing promoter can be a tissue scaffold. When the endoluminal stent graft is placed within the lumen, the segments of the healing promoter promote and induce the migration, proliferation, and adhesion of vascular cells to the endoluminal stent graft, increasing local healing. Thus, the healing time after implantation of the endoluminal stent graft can be shortened, and a more stable implant is produced that is less susceptible to the effects of migration and / or endoleak that may form on the side of the proximal neck.

Brief Description of the Drawings

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Mode for Carrying Out the Invention

[0061] The following detailed description and the accompanying drawings illustrate and exemplify various exemplary embodiments of the present invention. The description and drawings serve to enable those skilled in the art to make and use the present invention. Although the present invention is described with reference to preferred embodiments, those skilled in the art will recognize that changes may be made in form and detail without departing from the spirit and scope of the present invention. Accordingly, the following detailed description is to be regarded as illustrative rather than limiting, and it is intended that the appended claims (including all equivalents thereof) defining the scope of the present invention be so regarded.

[0062] As used herein, the term "proximal" is a broad term and should be given its ordinary and customary meaning to those skilled in the art, and without limitation, refers generally to the direction toward the physician during a medical procedure.

[0063] As used herein, the term "distal" is a broad term and should be given its ordinary and customary meaning to those skilled in the art, and without limitation, refers generally to the direction toward a target site within a patient's anatomical structure during a medical procedure.

[0064] As used herein, the terms "comprise", "include", "having", "has", "contain" and their variants are broad terms and should be given their ordinary and customary meaning to those skilled in the art, and are intended to be open-ended transitional phrases, terms or words that do not exclude the possibility of additional acts or structures.

[0065] As used herein, the term "body cavity" is a broad term and should be given its ordinary and customary meaning to those skilled in the art, and without limitation, refers to a body passage cavity that conducts fluids including, but not limited to, those of the digestive tract, bile duct, pancreatic duct, urinary tract, esophagus, and those of the human vascular system.

[0066] As used herein, the term "implantable" is a broad term and should be given its ordinary and customary meaning to one of ordinary skill in the art, and refers to the ability of a medical device to be placed at a location within the body, such as within a body cavity. Further, as used herein, the terms "implant" and "implanted" are broad terms and should be given their ordinary and customary meaning to one of ordinary skill in the art, and refer to the positioning of a medical device at a location within the body, such as within a body cavity.

[0067] As used herein, the terms "endolumenal", "intraluminal", and "transluminal" are broad terms and should be given their ordinary and customary meaning to one of ordinary skill in the art, and refer to an implantation procedure in which a medical device advances through a body cavity from a remote location to a target site within the body cavity. Endoluminal delivery may include implantation from an endoscope or catheter into the bile duct.

[0068] As used herein, the term "expanded mesh" is a broad term and should be given its ordinary and customary meaning to one of ordinary skill in the art, and refers to a mesh that opens when expanded. Refers to self-expanding and / or non-self-expanding configurations made of any generally rigid or elastic material that has a shape or arrangement and otherwise enables internal growth of the tissue and does not impede the flow of fluid through its walls, but is not limited thereto. Some prior art mesh stents have been used with polymer sheaths or covers. However, these sheaths must be stretched to increase their size. These materials exert a force that resists expansion, which tends to limit the final expanded size of the prior art mesh. Further, this resistance can make the expansion of the mesh more problematic. Alternatively, the sheath may be folded or bundled onto the prior art mesh when compressed, such that no force is applied during expansion. However, this method increases the overall size of the compressed prior art stent, such that a larger sized catheter is required for a stent of a given size.

[0069] As used herein, the term "hierarchical" is a broad term and should be given its ordinary and customary meaning to one of ordinary skill in the art and, in at least one aspect, refers to microstructures having larger and smaller dimensions relative to each other, i.e., microstructures of larger dimensions and microstructures of smaller dimensions, but is not limited thereto. In some examples, the microstructures of larger dimensions may support the microstructures of smaller dimensions. Generally, microscale features are understood to include structures having dimensions (e.g., length, width, height, pitch, and / or gradient) in the range of about 1 micrometer to about 10,000 micrometers. As used herein, microscale features may collectively be referred to as surface texture unless the context indicates otherwise.

[0070] As used herein, the term "tissue adhesive" is a broad term and should be given its ordinary and customary meaning to one of ordinary skill in the art, and includes, but is not limited to, a surface having a hierarchical micropattern that can resist translation in a direction perpendicular to and / or parallel to the target surface when in contact with the target surface. As an example, an apparatus that is a tissue adhesive is arranged in contact with a target surface and, when acted upon by some external force, can generate a peeling force and / or a shearing force.

[0071] As used herein, the term "cell promoter" is a broad term and should be given its ordinary and customary meaning to one of ordinary skill in the art, and includes, but is not limited to, a surface that can direct cells in a particular direction, and / or promote a particular type of cell to be disposed on the surface, and / or direct a particular combination of cells to be disposed on the surface, and / or promote a particular cell type while blocking other cell types. In one example, a cell promoter can heal tissue adjacent to the cell promoter surface faster and more strongly than some other tissue not adjacent to the cell promoter.

[0072] The term "antifouling surface" is a broad term and should be given its ordinary and customary meaning to one of ordinary skill in the art, and includes, but is not limited to, a surface that can resist the accumulation of molecules, microparticles, or cells. As an example, an antifouling surface can be a surface that suppresses the accumulation of substances from the environment in which the surface is disposed.

[0073] The term "Wenzel interface" is a broad term and should be given its ordinary and customary meaning to one of ordinary skill in the art, and refers to, but is not limited to, a surface having a surface texture consisting of a plurality of surface features that can draw water between the surface features of the surface texture when disposed in contact with a wet target surface.

[0074] The term "Cassie interface" is a broad term and should be given its ordinary and customary meaning to those of ordinary skill in the art, and without limitation, refers to a surface having a surface texture consisting of a plurality of surface features that prevent water from interpenetrating between the surface features of the surface texture when placed in contact with a wet target surface. when placed in contact with a wet target surface.

[0075] The terms "intrinsic mode", "wrinkle intrinsic mode", and "wrinkle mode" are broad terms and should be given their ordinary and customary meaning to those of ordinary skill in the art, and without limitation, refer to the natural wrinkles of a tissue surface when subjected to shear forces. The tissue intrinsic mode is clearly defined and characterized by the tissue's flexural modulus. A given tissue type can naturally wrinkle or develop spatial periodicity, which is characterized by the spectrum of these spatial periodicities.

[0076] The terms "Schallamach wave" and "Schallamach wrinkle" are broad terms and should be given their ordinary and customary meaning to those of ordinary skill in the art, and without limitation, refer to the generation of detachment waves known to occur during wear experiments using a target substrate. In some examples, Schallamach waves are explained in terms of the elastic instability of an elastomer surface. For example, if the surface of a device is designed to anticipate these waves by adopting a surface periodic structure that can be slightly lower in spatial frequency than the expected Schallamach waves, the Schallamach waves can be trapped in the periodic structure and dramatically increase the shear force required for translation. Such a "Schallamach-matching" design can reduce wear damage between the device surface and the target surface.

[0077] The terms "micro-pattern" or "microstructure" are broad terms and should be given their ordinary and customary meaning to those of ordinary skill in the art, and include, but are not limited to, textures of regular or irregular patterns (e.g., stent texture) where the shortest center-to-center distance (i.e., the distance between geometric centers, pitch) of adjacent textures (i.e., textures sharing a side) is greater than 1 micrometer. In a pattern of regular texture, each of the two geometric centers is equidistant from the side shared by the adjacent textures. In an irregular pattern of texture, the two geometric centers are not equidistant from the side shared by the adjacent textures. In an irregular pattern of texture, the spacing parameter can satisfy an average value, e.g., the average distance between microstructural centers.

[0078] The terms connected, coupled, and in communication refer to any form of interaction between two or more entities, including mechanical, electrical, chemical, magnetic, electromagnetic, fluidic, and thermal interactions. Two components can be coupled to each other even if they are not in direct contact with each other. For example, two components can be coupled to each other via an intermediate component.

[0079] Various medical devices for implantation within a body cavity are disclosed herein. Some embodiments relate to a medical drainage device that includes two or more flat, curved bends in a tubular member, each bend being capable of curving in an opposite direction with respect to an adjacent bend. For example, a pair of consecutive flat, curved bends can form a pigtail shape or a helical configuration. In some embodiments, the curved bend can define a meandering portion of a drainage lumen within the tubular member.

[0080] The medical drainage device disclosed in this specification can be described with respect to an exemplary bile duct stent embodiment that includes a tubular support member. However, embodiments of bile duct drainage stents can also exemplify other drainage devices such as ureteral stents, esophageal stents, or drainage catheters provided according to other embodiments. For example, the drainage stent can be configured for use within the ureter, urethra, esophagus, or blood vessel.

[0081] The subject matter of the present disclosure can be embodied in many different forms, but in this specification, various embodiments of the present disclosure will be described in detail. This description is an exemplification of the principles of the present disclosure and is not intended to limit the present disclosure to the specific embodiments illustrated.

[0082] For the purposes of the present disclosure, like reference numerals in the figures shall refer to like features unless otherwise indicated.

[0083] In some embodiments, the present disclosure relates to micro-patterned polymer coatings or surfaces for use in medical devices. In some embodiments, the micro-patterned polymer surface can be utilized in implantable medical devices such as stents, particularly for stents used in the gastroesophageal system including, but not limited to, the esophagus, bile duct, and colon stents, in order to reduce or prevent stent migration. In one or more embodiments, the micro-patterned polymer coating may include regularly or irregularly spaced micro-scale textures. In one or more embodiments, the micro-patterned polymer coating may include micro-scale textures of regular or irregular shapes (e.g., voids, spaces, channels, passages, etc.). In one or more embodiments, the micro-patterned polymer coating may include micro-scale textures that are regularly or irregularly spaced and shaped. In some embodiments, such micro-scale textures can, for example, promote controlled cell migration and tissue ingrowth.

[0084] The microstructure of the present invention may be capable of generating forces due to 1) hydrophobic / hydrophilic effects, 2) microtopology, 3) absorption chemistry, 4) morphological swelling, and / or 5) active mechanical interactions. These forces can be generated in a dry state, a moisture state, a wet state, or a combination thereof.

[0085] In some embodiments, the devices of the present disclosure may include anti-fouling aspects, in which case a microstructure exhibiting oleophobicity on the inner surface(s) of the stent may contribute to anti-fouling properties. In certain embodiments, the anti-fouling surface may include pores that can attract a film of water to form a super-nano hydrophilic structure and form a protective layer exhibiting anti-fouling properties.

[0086] In addition to anti-fouling properties, some devices may be able to produce a similar effect of self-cleaning. Self-cleaning strategies may present a surface topography similar to that of shark skin or butterfly wings, which are known not to necessarily inhibit deposition but rather to easily release accumulated materials from the microstructured surface.

[0087] In some embodiments, the micro-patterned surfaces can be modified with zwitterionic polymer brushes or polyelectrolyte multilayers to enhance their anti-fouling and / or self-cleaning properties. Further, in some embodiments, the anti-fouling properties can be combined with fluid transport functions. For example, a surface having a fine raised morphology can exhibit fluid transport and anti-fouling properties.

[0088] Antifouling properties can, in some embodiments, be associated with a drag-reducing microstructured surface. For example, the sharkskin morphology is known to have antifouling properties. One interesting aspect of the sharkskin microstructure related to antifouling ability is its ability to promote laminar flow. Turbulent flow across the surface is understood to cause fouling as a result of a reentrant fluid circuit that can rotate along the interface. Some microstructured surfaces can generate a hydrodynamic lift effect similar to the aerodynamic flow of air over an aircraft wing. Although the fluid cannot expand like a gas in the case of an aircraft wing, the lift effect of the microstructure can push nucleation particles away from the surface, potentially forming a particle-free fluid zone.

[0089] In a preferred embodiment, the stent comprises 1) immediate adhesion to the target lumen, 2) sealing, 3) fluid transport, and / or 4) an antifouling region.

[0090] Embodiments of the endoprosthesis as disclosed herein are shown in FIG. 3, which has a side cross-sectional view of the endoprosthesis. As shown in FIG. 3, the endoprosthesis 300 can include a polymeric wall 306. In one or more embodiments, the endoprosthesis 300 can be a preformed stent. In certain embodiments of the present disclosure, the endoprosthesis 300 can include a tubular member 308 having at least a portion with a constant diameter, and the tubular member 308 and / or one or more ends 309, 310 can include one or more tapers, or one or more flares, and / or other diameter variations. The endoprosthesis 300 shown in FIG. 3 can include an inner surface 312 and an outer surface 314 of the polymeric wall 306. The outer surface 314 can include one or more microstructural patterns disposed around the surface. In some embodiments, the hierarchical microstructural pattern 320 of the present invention on the outer surface 314 may cover only a portion of the outer surface. In some embodiments, the hierarchical microstructural pattern 320 may cover from 1% to 100% of the outer surface 314. In some embodiments, the hierarchical microstructural pattern 320 can cover 5%, 10%, 15%, 20%, 25%, 30%, 35%, 40%, 45%, 50%, 55%, 60%, 65%, 70%, 75%, 80%, 85%, 90%, 95%, or 99% of the outer surface 314. In other embodiments, as shown in FIG. 3, the outer surface 314 can include a plurality of microstructural patterns disposed around the surface such that the surface is covered from 1% to 100% by the plurality of patterns. It will be readily understood that the proportion of each microstructural pattern disposed around the outer surface 314 is within the range of the recited proportions specified above and can total 100% or less.

[0091] In some embodiments, the microstructural pattern 320 of the outer surface 314 can include hierarchical microfeatures 321, and smaller microfeatures 323 can be disposed around larger microfeatures 325. In some embodiments, the microstructural pattern 320 can include hierarchical microfeatures 323, 325, and the larger microfeatures 325 include recurved pillars 322. In some embodiments, the recurved pillars 322 can include a T-shaped configuration 324 at their top section. In certain embodiments, the recurved pillars 322 can include smaller pillars 326 disposed thereon. In some embodiments, the smaller pillars 326 may be disposed around the upper surface of the recurved pillars 322. In some embodiments, the recurved pillars 322 may be arranged in a triangular pattern with respect to adjacent pillars. The recurved pillars 322 may be arranged such that the pitch or spacing between adjacent pillars is 1 to 500 microns, 1 to 250 microns, 25 to 250 microns, or 25 to 100 microns. In some embodiments, the recurved pillars 322 can have a diameter of 1 to 500 microns, 1 to 250 microns, 1 to 100 microns, 1 to 50 microns, or 10 to 50 microns. In some embodiments, the recurved pillars 32 can have a height of 1 to 500 microns, 1 to 250 microns, 1 to 100 microns, 1 to 50 microns, or 10 to 100 microns. In certain embodiments, the recurved pillars 322 can have a pitch or spacing between adjacent pillars of 25 to 100 microns, a diameter of 10 to 50 microns, and a height of 10 to 100 microns. In embodiments where the recurved pillars 322 include a T-shaped top configuration, the top of the T-shaped configuration can be circular with a diameter that is 1.2 to 2.5 times the diameter of the base portion of the recurved pillar.

[0092] In some embodiments, the second pillars 326 disposed around the recurved pillars 322 can have a pitch between adjacent pillars of 10 to 50 microns, a diameter of 10 to 150 microns, and a height of 1 to 10 microns. In some embodiments, these second pillars 326 may be made of a liquid-swellable polymer.

[0093] In certain embodiments, the target tissue can be retained between the large microfeatures 322, 325. . In certain embodiments, the tissue may be retained between the T-shaped configurations 324 of the recurved pillars 322. In some embodiments, the T-shaped configuration 324 can have swelling properties that can provide a pincer action on or around the tissue 328, whether in contact or non-contact.

[0094] In at least one embodiment of the present disclosure, the outer surface 314 can include a microstructured pattern for transporting fluid.

[0095] As shown in FIG. 3, the inner surface 312 can include a microstructured pattern 330 that includes microridges 334 that can be fabricated with microfeatures having a ridged shape. In certain embodiments, the microridges 334 can include an airfoil-like profile with a tapered end and a central portion that is higher than the ends. The microstructured pattern 330 can include a plurality of microfeatures of the microridges 334 whose edges can be separated in a spaced-apart state between adjacent features of 1 nm to 100 microns, 10 nm to 50 microns, or 100 nm to 10 microns (see FIG. 4 for further exemplification, microridge 434). As shown in FIG. 4, in some embodiments, the microridges 434 can have a length of an axial dimension 442 that can be longer than the width 444 of the microridges 434. In certain embodiments, the ridges 334, 434 can form groupings 340, 440 or islands, and a single microfeature can be considered a first microstructural level, and the groupings or island shapes 340, 440 can be considered a second microstructural level. The two microstructural levels can be expected to work together to facilitate a laminar flow through the stent lumen.

[0096] In some embodiments, the microstructured pattern 320 of the outer surface 314 can include microfeatures in the form of microridges 318 for fluid conduction properties. The microridges 318 can have a pitch of 1 to 500 microns, 1 to 250 microns, 1 to 100 microns, 1 to 50 microns, or 5 to 50 microns. The microridges 318 can include a width of 1 to 100 microns, 1 to 50 microns, 1 to 40 microns, 1 to 30 microns, or 1 to 20 microns. The microridges 318 can include a height of 1 to 500 microns, 1 to 250 microns, 1 to 100 microns, 1 to 50 microns, or 5 to 50 microns. Referring to FIG. 3A, the microridges 318 may be arranged such that the length of the microridges 318 is positioned in a circumferential pattern with respect to the central axis 350 of the endoprosthesis (i.e., along the "y" axis shown in FIG. 3A), or the microridges 318 may be arranged such that the length of the microridges is positioned axially with respect to the central axis of the endoprosthesis (i.e., along the "x" axis shown in FIG. 3A). The plurality of microridges 318 may be parallel, convergent, or diverging. In certain embodiments, the branching portions of the microridges may be directed towards the ends of the stent to draw fluid from the interfacial volume defined by the outer wall of the stent and the surface of the target lumen.

[0097] In at least one embodiment shown in FIG. 4, the inner surface 412 can include at least one pattern of micro - ridges 434. In some embodiments, the inner surface 412 can include a second pattern of micro - ridges that can include a plurality of additional micro - ridges. As disclosed above and illustrated in different manners, in some embodiments, the length dimension 442 of the micro - ridges 434 may be oriented in an axial position relative to the central axis of the implant prosthesis. In some embodiments, the length 442 of the micro - ridges 434 may be oriented in a circumferential pattern relative to the central axis of the implant prosthesis. In still other embodiments having a plurality of micro - ridges 434, a first portion of the plurality of micro - ridges may be oriented in an axial configuration and a second portion of the plurality of micro - ridges may be oriented in a circumferential configuration relative to the central axis of the implant prosthesis. The micro - ridges 434 have an airfoil profile that can direct microparticles away from the stent substrate surface 412 can do.

[0098] Referring now to FIG. 5, in certain embodiments, the fine structure pattern 530 on the inner surface may be arranged in a sine wave distribution 502 for various lengths and / or heights of the fine features (shown in FIG. 5). The grouping of the fine structures 540, or the islands as described above, may be composed of micro ridges 534, and the grouping or islands 540 may be regarded as a first fine structure level, and the micro ridges 534 may be regarded as a second fine structure level. The sine wave arrangement 502 is shown in the "bird's-eye view" and "side view" of FIG. 5 as an exemplary reference. The central positions 512 of the individual micro ridges 534 may be equally spaced in various geometric patterns such as a square lattice pattern or a triangular pattern. Further, the micro ridges 534 can be arranged in a uniform array or a non-uniform array. Further, the grouping or islands 540 may be arranged in a similar manner, and the grouping may be arranged relative to each other in a geometric pattern such as a square or grid pattern, or in a uniform or non-uniform pattern. Further, referring to both the individual micro ridges 534 and the grouping / islands 540, one subset may be arranged in a geometric manner, or in a uniform or non-uniform manner, and another subset may be arranged differently, and the same applies to other subsets.

[0099] Referring now to FIG. 6, an embodiment is shown including a longitudinal cross-sectional view of an in vivo prosthesis device 600 having a substrate 602 including an outer surface and an inner surface, the outer surface including an external sealing microstructure 604. As shown in FIG. 6, the in vivo prosthesis 600 can have a first end 601 and a second end 603. In some embodiments, the external sealing microstructure 604 can be hierarchical, having at least a first microstructure disposed hierarchically around a second microstructure, as described elsewhere herein. In some embodiments, the in vivo prosthesis device 600 can further include an anti-migration microstructure pattern 606. In some embodiments, the device 600 can include a flare end 608. In some embodiments, the device 600 can include anti-fouling microstructure patterns 610 and 612 disposed around the inner surface 611. In certain embodiments, the in vivo prosthesis device 600 can include a fluid conducting microstructure pattern 614. In other embodiments, the in vivo prosthesis device 600 can include a combination of different microstructure patterns including a sealing microstructure pattern 604, an anti-migration microstructure pattern 606, anti-fouling microstructure patterns 610, 612, and a fluid conducting microstructure pattern 614. In yet another embodiment, the device 600 can include any combination of the aforementioned microstructure configurations.

[0100] As shown in FIG. 6, the outer surface 616 of the flare end 608 can be smooth or can be decorated with a microstructure pattern 618. In some embodiments, the external microstructure pattern 604 can include a sealing configuration such as the previously identified sealing microstructure 604 and can be composed of first pillars 620 having a diameter of 10 to 100 microns, a pitch of 20 to 200 microns, and a height of 10 to 100 microns. In some embodiments, the sealing microstructure can further include second pillars 622 disposed around the first pillars 620, the second pillars can have a diameter of 1 to 10 microns, a pitch of 2 to 20 microns, and a height of 1 to 10 microns.

[0101] In some embodiments of apparatus 600 comprising an anti - movement fine - structure pattern 606, the fine - structure pattern may comprise a first two - dimensional sine - wave fine - structure 624 that can have a peak - to - peak distance (pitch) of 50 to 1000 microns and a peak height of 50 to 2000 microns. The anti - movement fine - structure pattern 606 disclosed herein may further include a second set of fine - structures 626 that can have a diameter of 10 to 100 microns, a pitch of 20 to 200 microns, and a height of 10 to 100 microns. Further, one embodiment of the anti - movement fine - structure pattern 606 disclosed herein includes a third set of fine - structures 628 that can have a diameter of 1 to 10 microns, a pitch of 2 to 20 microns, and a height of 1 to 10 microns. This can be the case. In certain embodiments, the anti - fouling fine - structure pattern 610 can include nanoparticles 630 randomly dispersed around the surface of the device. In certain embodiments, the nanoparticles 630 may be dispersed around the inner stent surface 61. In some embodiments, the circularly arranged pillars disposed around the inner surface 634 act as nucleation islands that cause preferential thinning deposition in response to fluid flow within the stent lumen 636 and can have a diameter of 1 to 10 microns, a pitch of 2 to 20 microns, and a height of 1 to 10 microns. The fluid - conducting fine - structure 614 may include through - holes that conduct fluid from the outer stent surface 638 to the stent lumen 636.

[0102] In certain embodiments, the anti - movement fine - structure pattern 606 can also include a peak - to - peak distance of the first fine - structure 624 selected to match the natural wrinkle spacing suitable for aligning target surface wrinkles induced by shear forces within the space between the peaks of the fine - structure 624.

[0103] The anti - fouling nanoparticles 630 may range in size from 1 to 100 nanometers and may provide a hydrophobic surface. The size of the fine features 628 can be selected to be more lipophilic with respect to the nanoparticle surface 630 such that deposits can accumulate on the circularly arranged islands of the fine features 628.

[0104] Referring now to FIGS. 7A, 7B, and 7C, three embodiments are shown with respect to the antifouling microfeature 700. In one or more of these embodiments, the microstructured surface can create a hydrodynamic effect that can push aside the microparticles entrained in the fluid flow. In the upper diagram of FIG. 7, the microstructure 702 can include a top having an airfoil design with upwardly facing wing tips 704 disposed at one or more distal ends of the upper surface. The wing tips 704 may be configured to reduce turbulence of the fluid along the microstructure. In the lower left of FIG. 7, the microstructure 706 can include a configuration mimicking shark skin, which can include a top 708 having a serrated edge attached to a flared base pillar 710. In some embodiments, the top 708 may be planar or curved. In some embodiments, the top 708 can include a central portion having a bulk thicker than the bulk of the edge. In the lower right of FIG. 7, the microstructure 712 is a combination of the foregoing embodiments, and the top 708 can include a serrated edge along with a set of microstructures of fins 714 protruding outwardly from the top surface.

[0105] In one or more embodiments, one or more textures may extend completely through the thickness of the coating. In one or more embodiments, one or more of the textures are blind textures (e.g., textures having cavities, indentations, bottoms, textures that do not extend from a second surface to a first surface).

[0106] In some embodiments, as shown in FIGS. 3-6, the micropillars may be of any geometric shape including, but not limited to, cylinders, prisms having a cylindrical, rectangular or polygonal base, pyramids, bumps, squares, ellipses, etc. In some embodiments, the micropillars may be the above combinations arranged in a hierarchical manner. The hierarchical arrangement results in an overall texture that can be a complex and non-traditional shape having multiple protrusions, valleys, and / or ridges on multiple surfaces that do not define a cross-section such as circular, square, polygonal, etc. Individually, the texture may be, for example, micropillars having a circular cross-section, a square cross-section, a rectangular cross-section, a star cross-section, a hexagonal cross-section, a pentagonal cross-section, a heptagonal, an octagonal cross-section, a non-angular cross-section, a decagonal cross-section, other polygonal cross-sections, or a cross-section of a non-traditional shape. In some embodiments, the cross-section of any particular type of texture structure may have less impact on the surface properties compared to the surface energy domains generated by the juxtaposition and lamination of different texture structures.

[0107] Those skilled in the art will appreciate that the structural dimensions (height, width, diameter, pitch, gradient, and length) can be considered when designing the surface to produce the desired effect. One or more of the microstructural textures as described elsewhere in this specification can have a cross-section having a first dimension "h", which can be the maximum distance between the outer surface of the base and the end of the structure, and a second dimension "d", which is the maximum distance between two opposing side surfaces (e.g., of a pillar). In some embodiments, "h" may be related to the "height" of the structure, and "d" may be related to the "diameter" of the structure. In some embodiments, "h" may be the overall height, or "h" may refer to a specific length of a component of the structure. The same applies to "d", where the diameter may be the overall diameter of the structure or a specific diameter of a component of the structure. For example, in an embodiment having a circular cross-section, the second dimension may be the diameter. In the case of a square cross-section, the diameter can be measured from two opposite side surfaces. In the case of a rectangle, the major dimension may be between two opposite short sides. In the case of a star cross-section, the major dimension can be measured between two opposite points. Also, in the case of a hexagonal cross-section, the major dimension may be between two opposite points. In some embodiments, the second dimension "d" may be between the midpoints of two opposite sides. In at least one embodiment, the radial cross-section of the micropillar has at least four sides.

[0108] Embodiments of the present disclosure contemplate polygonal cross-sections that may include all sides of equal length, or combinations of sides of equal and unequal lengths, or all sides of unequal lengths. Embodiments of the present disclosure contemplate a plurality of pillars of a plurality of cross-sectional shapes, including conventional shapes (e.g., circular, square, rectangular, hexagonal, polygonal, etc.) and non-conventional shapes having a perimeter at least partially curved. In at least one embodiment, the micropillar may be a solid structure. In other embodiments, the micropillar may be partially solid. In still other embodiments, the micropillar may be a hollow structure. In at least one embodiment, each micropillar may have a constant cross-section, but in other embodiments, the micropillar may have a variable cross-section. In at least one embodiment, the micropillar structure may extend perpendicularly from the base. In at least one embodiment, the micropillar structure may extend at a non-perpendicular angle from the base, and the geometric center of the end of the micropillar may be laterally offset from the geometric center of the region of the base covered by the micropillar. For example, the longitudinal axis of the micropillar extending through the geometric center of the lateral cross-section can form an angle of less than 90 degrees with the base. In at least one embodiment, the plurality of micropillars can be arranged in a hierarchical arrangement in one or more specific micropatterns.

[0109] In one or more embodiments, the texture can take any of the shapes and dimensions described elsewhere in this specification. Generally, the hierarchical arrangement can include a base structure. In some embodiments, the base structure can be flat, can vary continuously like a sine wave profile, can be stepped like, for example, ascending and descending steps, can be perforated, or can vary otherwise in a random or regular pattern. For example, in a two-dimensional sine wave profile, the pattern can be characterized by a wavelength or a wavelength range. One aspect of the present invention is understood to include a second set of textures that can be disposed on the base structure. The second texture can be disposed as pillars, ridges, pyramids, and / or the like, as enumerated above. This second set of textures can also include characteristic dimensional measurements that can include pitch, height, diameter, width, gradient, and the like. In certain embodiments, the dimensional measurements of the base can be larger than the dimensional measurements of the second set of textures. In some embodiments, the ratio of the first measurement to the second measurement is between 10 and 0.5. In certain embodiments, there can be a third set of textures disposed on the second set of textures and optionally on the first set of textures located between the structures of the second set of textures. Depending on the desired effect, the ratio between these dimensional measurements can be adjusted to generate the desired effect. However, simply "adjusting" the dimensional measurements to produce the desired effect is not a trivial task, and it will be understood that thorough experimentation must be done to establish the dimensional measurements to produce the desired effect. One cannot simply select various features and simply produce the desired result. Small changes in one-dimensional measurements or different geometric shapes can have an undesirable effect on the properties of the microstructured surface.

[0110] In embodiments where the microstructure can provide an anti-fouling effect, the pitch of adjacent microstructures, such as pillars, relative to their height may be relatively small. For example, the height of the microstructure may be 1 to 10 times the pitch between the microstructures. The higher the ratio of height to pitch, the more hydrophobic the surface tends to be and the lower the surface energy. Low surface energy structures may tend to resist the deposition of ionic moieties that may be typical of biological tissues. If the desired effect of the microstructure surface is to promote cell migration along the surface, the structural dimensions can be selected to create a surface energy gradient along the surface. Such structural dimensions and positions can be designed such that cells can easily bridge and migrate along the structure and thereby move across the surface. In contrast, a microstructure surface with deep valleys disposed around the surface may tend to impede cell migration. It will be appreciated that cells rely on the continuity of attachment sites to propagate along the surface. Thus, a combination of tall pillars that are closely spaced apart (i.e., small pitch) such that cells do not easily fit between adjacent pillars can have the desired effect of promoting the propagation of cells across the surface without the cells growing into the surface. It will be appreciated that in-growth of cells onto the stent surface may be particularly undesirable due to the complications and problems that can arise in such scenarios. Instead, a microstructure surface with appropriate dimensions and positions of the structure can direct cells towards tissue defects for cell repair without in-growth of cells, which can result in the stent being difficult to remove. In some embodiments, the stent may be textured to resist movement relative to the deployment site. A surface texture that resists movement may typically include a Wenzel-Cassie wetting state. Such surface textures tend to create zones of hydrophilic attraction and hydrophilic repulsion in close proximity to each other, thereby creating a force that resists the movement of the stent.

[0111] In certain embodiments disclosed herein, the apparatus of the present invention may be a wire fabric stent. In some embodiments, the spacing of the wires relative to each other may match the natural modes of the tissue in which the stent is deployed. The natural modes may be bending natural modes, creep natural modes, or both. When one or more natural modes are excited by the deployment of the stent, the anti - migration coating can deform naturally to engage the target natural mode(s). In some embodiments, the stent structure may be configured to induce a target microstructure in the polymer coating and then make the coating thinner, enabling the stent to deploy more easily when expanded.

[0112] In some embodiments, close contact between the surface texture and the target lumen surface is desirable. In some embodiments, a gap between the surface texture and the target surface may be desirable. In certain embodiments, the gap may, on average, be less than about twice the height of the maximum surface texture height. When there is a fluid or gas gap between the surface texture and the target surface, the adhesion of the device to the surface does not depend on frictional engagement or any interlocking mechanism between the fine features of the device (e.g., micropillars, texture, etc.) and the target tissue. Instead, there is a hydrodynamic engagement between the surfaces that produces an anti - migration effect. Conversely, if frictional engagement with the tissue is desired, such a function can be added to the surface pattern herein by designing at least a portion of the surface features to provide such engagement. Thus, in at least one embodiment, one or more specific microstructures having micro - pattern geometries and dimensions suitable for a particular application (e.g., anti - fouling, promotion of biological tissue formation, desired anti - migration properties, etc.) are selected.

[0113] In one embodiment, all of the micropillars within the micropattern may have the same shape, and in other embodiments, the micropillars may vary in shape along the polymer coating, along a portion of the polymer coating, or at discontinuous portions of the polymer coating. Thus, in at least one embodiment, the micropattern can include a portion where the micropillars have a first configuration and a portion where the micropillars have a second configuration. Further, embodiments may include a polymer coating having only one micropattern or a polymer coating having a plurality of micropatterns. Thus, the polymer coating can be tailored to specific structural features and desired characteristics of the body cavity while using a single stent.

[0114] Similarly, in one or more embodiments, the texture may be configured and arranged in the same manner as described herein for micropillars disposed on a two-dimensionally sinusoidally varying base. That is, in at least one embodiment, the texture within the micropattern may have a discrete shape combined with a continuous shape, and in other embodiments, the texture may vary in shape along a polymer coating. Thus, in at least one embodiment, the micropattern can include a portion where the texture has a first orientation and a portion where the texture has a second orientation. Further, embodiments can include a polymer coating having just one micropattern (e.g., a micropattern such as a random texture, micropillars, etc.), or a polymer coating having a plurality of micropatterns (e.g., two or more different micropatterns of texture, two or more micropatterns of micropillars, one or more micropatterns of micropillars combined with one or more micropatterns of texture). Thus, the polymer coating can be tailored to the specific structural and / or anatomical characteristics of a body cavity (e.g., a blood vessel, etc.) and can achieve a desired frictional engagement or interlock while using a single stent. In one or more embodiments, the micropattern can include one or more textures in combination with one or more micropillars (e.g., a micropattern that alternately includes a first number of textures and a second number of micropillars, etc.). In one or more embodiments, the polymer coating may include a micropattern of micropillars and a micropattern of texture, and the micropatterns may or may not overlap.

[0115] In some embodiments, the ends of protrusions such as the micropillars furthest from the outer surface of the base can be shaped to improve tissue adhesion. In one or more embodiments, the ends can be tapered, pointed, rounded, concave, convex, serrated, and / or frayed. The end of each second protrusion can also include a plurality of first pillars on a scale even smaller than the second micropillar.

[0116] Similarly, in some embodiments, the second surface of the tissue engagement portion can be adapted to improve tissue adhesion (e.g., molded, textured, modified, etc.). In one or more embodiments, the side and / or bottom surfaces of the texture can be tapered, grooved, punctured, concave, convex, serrated, and / or frayed.

[0117] In at least one embodiment, the protrusion can also include end features such as a mushroom-shaped termination having an involute curve, a downward spine, and / or a plurality of bumps having a concave center extending outward from the surface of the micropillar. In some embodiments, the end surface can include a plurality of depressions extending inward from the surface of the micropillar, a plurality of ridges concentrically disposed on the end surface of the micropillar, a tip that is softer or more rigid than the rest of the protrusion at or near the end of the protrusion, a frayed tip, a convex tip tip, a flared tip, a concave tip, a tip having a first dimension larger than the diameter of the micropillar column extending outward from the base and the tip, and / or other features that can be coated with a thin layer of a material having a specific surface energy, which can be useful for distinguishing the surface energy of adjacent surfaces, thereby establishing a Wenzel-Cassie domain useful for improving the grip, stiffness, and / or flexibility characteristics of the interface between the device and the tissue, and any combination of these features.

[0118] In at least one embodiment, the tip may be composed of a material different from the rest of the protrusion. Similarly, the end face and / or side face of the texture can be shaped to improve tissue adhesion similar to that described above for the micropillars. For example, the texture can be a smooth surface, a rough surface, a plurality of bumps extending outward from the surface of the texture to create a capillary action aspect, a plurality of depressions extending inward from the surface of the texture, a plurality of ridges on the surface of the texture, a frayed end, a convex upper end, a flared lower end, a concave upper end, a bottom having a first dimension larger than the characteristic diameter of the protrusion extending between the second surface and the end, and / or developing a capillary suction aspect for gripping, influencing a flow aspect useful for stiffening the interface between the device and the tissue, a sliding or flowing aspect on the microscale, and / or other features such as any combination of those features that can improve the flexibility characteristics of the device.

[0119] In at least one embodiment, the micro-pattern can include micro-ridges and / or textures that are equally spaced (pitched) at an equal distance from a first distance within the micro-pattern in a first region (s) of the base and equally spaced at an equal distance from a second distance (which can be different from the first distance) within the micro-pattern in a second region (s) of the base. In at least one embodiment, the micro-pattern is a curved array. In at least one embodiment, the micro-pattern of the first curved array of microstructures can intersect at an angle with the second curved array of microstructures to form a grid pattern (e.g., a square array). In at least one embodiment, the micro-pattern of the microstructures is a regular n-sided polygon array (e.g., a hexagonal array), and the micropillars or textures may be present at the center of the microstructures forming the polygon, or may not be present at the center of the polygon at the center of the microstructures forming the polygon. In other words, in the micro-pattern, the micropillars and / or textures are arranged in an array within the micro-pattern of the microstructures, and the rows and columns of the array may or may not be perpendicular.

[0120] In one or more embodiments, each micropillar or texture may have a longitudinal axis, and the micropillars may be axially aligned in at least one of the axial direction (e.g., arranged in rows parallel to the longitudinal axis of the device) and the circumferential direction (e.g., arranged in rows extending circumferentially around the longitudinal axis of the device) of the device. In at least one embodiment, the micropattern of micropillars or textures includes any or all of the features described in the previous paragraph.

[0121] In some embodiments, the micropattern may cover only a portion of the base rather than the entire base. The micropattern of micropillars or textures may be arranged in a spiral on the base. In one or more embodiments, a first micropattern may be arranged longitudinally along the base, and a second micropattern may be arranged circumferentially around the base, such that the micropatterns form a mosaic configuration. The micropillars may be arranged in one row (e.g., parallel to the longitudinal axis of the stent), or in a plurality of rows that are continuous or discontinuous rows (e.g., aligned row segments separated by gaps). The discontinuous rows (and circumferentially oriented columns) can extend across the mosaic structure, and the length of the discontinuity is five times the separation distance.

[0122] Regarding the materials used for the polymer coating, it can be useful for the materials to have various properties that are useful in the environment in which they are produced and deployed. For example, the materials can cause an adaptable contact with tissue, withstand the processes for causing the polymer coating, and / or be flexible and / or elastic enough to accommodate stenting mechanisms such as elongation and conformity to tortuous anatomical structures. Examples of materials that can be considered include, but are not limited to, flexible silicone, polyurethane, hydrogel, mucoadhesive substrates, pressure-sensitive adhesives, and other suitable elastomers such as synthetic rubber. In some embodiments, a more rigid substrate can be used in an individual configuration. Examples of acceptable rigid materials include, but are not limited to, polypropylene, polylactic acid polymers, PEEK, and polyacryl.

[0123] In one or more embodiments, a coating having a micropattern can include and / or be formed from a protein structure derived from an organism (such as collagen, etc.). Other acceptable materials can include any flexible, biocompatible, and non-biodegradable polymers. For stent applications for symptomatic treatment, it can be useful for the coating to include one or more non-biodegradable polymers and / or materials having a degradation profile that can be useful for specific stent applications and implantation sites. In one or more embodiments, the coating can be biodegradable, for example, to enable stent removal (such as after a part or all of the coating has degraded). Applications where it can be useful to remove the stent include support during perforation healing, dilation of benign structures, and bridging to surgery.

[0124] In at least one embodiment, a polymer coating having micropillars and / or ridges can include polymerized hyaluronic acid that can conform to the lumen wall in a biochemical manner. Hyaluronic acid can also swell in a liquid environment. A microstructured device composed of hyaluronic acid may be able to grip the target tissue in a pincer movement due to the swelling of the microstructure.

[0125] In at least one embodiment, the polymeric coating can include at least one therapeutic agent. In other embodiments, an additional coating may be applied to the polymeric coating, and the additional coating includes a therapeutic agent. Whether part of the polymeric coating or an additional coating, the therapeutic agent can be a drug or other pharmaceutical, such as a non-genetic agent, a genetic agent, cell material, a protein-depleted extracellular matrix, and the like. Some examples of suitable non-genetic therapeutic agents include, but are not limited to, antithrombotic agents such as heparin, heparin derivatives, vascular cell growth promoters, growth factor inhibitors, paclitaxel, and the like. When the agent includes a genetic therapeutic agent, such genetic agents can include, but are not limited to, DNA, RNA, mRNA, siRNA, and their respective derivatives and / or components, particularly when such genetic derivatives are bound to the polymeric surface. The therapeutic agent may also include cell material, which may include cells of human and / or non-human origin, and their respective components and / or their derivatives, but is not limited thereto. In one or more embodiments, suitable therapeutic agents can include organic small molecules, peptides, oligopeptides, proteins (such as the "hedgehog" protein, etc.), nucleic acids, oligonucleotides, gene therapy agents, non-gene therapy agents, vectors for the delivery of gene therapy agents, cells, and / or therapeutic agents identified as candidates for vascular therapy regimens, and combinations thereof.

[0126] In one or more embodiments, one or more therapeutic agents may be included within or on a polymeric coating that includes micropillars and / or ridges. In some embodiments, using plant derivatives such as terpenes, particularly triterpenes, various acids, particularly boswellic acids, and various phenols and antioxidant plant derivatives as therapeutic agents is possible.

[0127] In one or more embodiments, the base may be formed from the same material as the structure of the micropillars and / or tissue engagement portions. In one or more embodiments, the micropillars and / or structure are formed from one material and the base is formed from a different material. In one or more embodiments, the micropillars and / or structure are formed of layers of materials, which may be the same material or different materials depending on the properties required for the desired interaction between the device and the target tissue. The difference in surface energy between adjacent hierarchical sites can play a role in establishing the Wenzel-Cassie interface of the present invention, so the difference in surface energy can be enhanced by coating some microstructural chips or domain walls with thin layers of materials having the desired ion content. From the perspective of surface energy, it can be understood that surface texture and surface chemistry are interchangeable, so chemical coatings may be used instead of surface texture.

[0128] The devices of the present disclosure can be understood to have less wear localization interaction with the luminal wall of the target tissue when inserted into the lumen, compared to similar devices / stents that rely on frictional engagement with tissue. As a result, removal of the devices disclosed herein can be made easier with conventional removal techniques. In at least one embodiment, the device can comprise a suture or removal loop at one end. In at least one embodiment, the removal loop may be provided at the distal end of the device. It should be noted that references to the term "distal" herein refer to the direction away from the operator of the device of the present disclosure, and references to the term "proximal" refer to the direction towards the operator of the device of the present disclosure. Sutures or removal loops are well known in the art for removing endoprostheses, but the suture or removal loop is provided at the proximal end of the stent, that is, the end closest to the operator. Here, the suture or removal loop is applied to the end opposite the endoprosthesis. In at least one embodiment, the operator may pass the operator's tool through the lumen of the endoprosthesis, grasp the loop at the distal end, and then grasp the loop by applying an axial force to the loop. The distal end of the endoprosthesis may be folded inward and pulled through the lumen of the endoprosthesis itself (i.e., device inversion). Thus, with such a removal method, the micropillars can be peeled off from the blood vessel wall while removing the endoprosthesis by turning the stent inside out. This removal technique may be desirable because the surface texture of the present disclosure can reduce adhesion with peeling force (perpendicular displacement) compared to adhesion with shear force (parallel displacement). In other embodiments, the operator may grasp the loop from outside the endoprosthesis or at the end of the endoprosthesis.

[0129] To manufacture an intravascular prosthesis, several methods can be employed. The polymer coating is formed (e.g., molded) separately from the stent (e.g., as a polymer film, hydrogel film, thin fibrous network, etc.) and then adhered to the stent (e.g., the outer surface of the stent) by an optional adhesive layer (e.g., applied to at least a part of one or both of the first surface of the base and the outer surface of the stent) disposed between the outer surface of the stent and the base (e.g., the first surface) of the polymer coating. A polymer coating having a micro-pattern of fine features (e.g., micropillars, textures, etc.) can be produced by injecting a polymer material into the reverse mold of the micro-pattern. Also, the polymer material can be extruded through the mold using a vacuum pump system. In at least one embodiment, the polymer coating can be created using soft lithography techniques.

[0130] In one or more embodiments, etching techniques can be used to create the coating, removing material from a layer of coating material to create a micro-pattern of the polymer coating. In yet another embodiment, a technique called hot embossing is used It can be done, which includes punching out the partially cured polymer into the desired shape of the polymer coating and then curing it before applying it to the stent. The stamping may or may not include the use of a solvent. In one or more embodiments, the stent may be coated by any suitable method (e.g., spraying, dipping, injection molding, etc.), and then a texture may be introduced into the coating after the stent coating. In some embodiments, a fibrous network having a microscale texture (e.g., voids) can be formed by electrospinning one or more fibers onto the pre-coated stent. In one or more embodiments, a laser ablation process can be used to remove material from the coating using one or more laser beams of appropriate size (e.g., the same or different sizes depending on the desired pattern) to form one or more micropillars and / or one or more microridges.

[0131] In one or more embodiments, one or more portions of the coating may be deployed into the body cavity separately from the stent (e.g., as one or more pads). Then, for example, a gluco - adhesive can be applied to an applicable portion of the stent intended to adhere to the coating (e.g., a biocompatible pad) before deployment. The radial expansion force of the stent during and after deployment can activate the adhesive and adhere the stent to the coating pre - deployed in the body cavity. The gluco - adhesive may be an alginate. Alginate on a smooth surface may dissolve into the tissue volume, and thus its adhesive effect is temporary. However, such an adhesive placed in the valley section of a hierarchical texture can serve two roles: 1) immediate adhesion and 2) the mucosal adhesive can act as a medium that can strengthen the domain wall between the hydrophilic and hydrophobic regions. The gluco - adhesive may be able to reinforce the natural Wenzel - Cassie boundary and can give a structural aspect to the domain wall rather than simply an equipotential surface. The glucose adhesive can effectively solidify the initially established Wenzel - Cassie domain.

[0132] In one or more embodiments, a polymeric coating having a negative texture (e.g., micropores) may be formed by using a technique called particle dissolution (e.g., salt dissolution), and the composite material is formed from one or more polymeric materials and one or more microparticles (e.g., soluble salts), and then one or more microparticles (e.g., salts) are dissolved from the composite material (e.g., using a solvent) to yield a composite and / or polymeric material having a texture or voids from which one or more microparticles (e.g., salts) have been removed. The salt can be an alginate that uses ion concentration to provide capillary effect characteristics to draw liquid into the voids formed by dissolution.

[0133] In one or more embodiments, a polymeric coating having multiple textures may be formed by a technique called electrospinning (e.g., using charge to draw very fine fibers from a liquid), and the polymeric coating includes a plurality of fibers disposed on or near a base that forms a texture (e.g., a network of textures, a network of voids) between the fibers. A technique called electrowriting is the same concept except that the filaments are directed at a target surface in a controlled manner using standard xy printing techniques. In particular, in harmony with the desired Wenzel-Cassie structure, the directed electrospinning method can accurately lay individual fibers of different materials on top of pre-laid fibers. In at least one embodiment, the stent surface includes alternating fibers of hydrophilic and hydrophobic materials arranged in an alternating pattern stacked to depict a polygonal grid, e.g., a rectangular grid. Such a directed electrospun grid surface can provide a dual functionality of localizing the stent and promoting the growth of healthy tissue, where fibrosis is downregulated and functional muscle tissue and angiogenesis are upregulated. It has been recognized that the density of such stacked polygonal meshes can promote various macroscopic tissues including repair morphology, kinetic morphology (e.g., layers of muscle tissue), and pressure wall formation morphology. The pressure wall formation morphology can be understood to be particularly important in the repair of fluid-conducting lumens.

[0134] In one or more embodiments, the use of salt leaching and / or electrospinning can be used to provide a polymeric coating having one or more textures that form a network of textures (e.g., a plurality of textures in fluid communication along a base). In some embodiments, when the polymeric coating includes a network of textures that penetrate the base, or when the base has openings that promote tissue growth, intracellular colonization can be enhanced. In one or more embodiments, any of a variety of therapeutic agents (e.g., growth factors), including but not limited to fibronectin, and those described elsewhere herein can be included on, within, and / or in combination with the network of textures to promote tissue ingrowth when the micropatterned polymeric coating contacts the tissue.

[0135] In at least one embodiment, the coating can be shaped as a substantially tubular structure having a lumen defined by the base of the coating. A temporary adhesive layer or alternatively a soft hydrogel layer can be applied to at least a portion of the outer surface of the stent or the base of the coating. In at least one embodiment, the adhesive layer may substantially cover the entire outer surface of the base of the coating. The stent can be inserted into the lumen of the coating as a separate element. In at least one embodiment, heat and / or pressure may be applied to ensure proper adhesion of the coating to the stent via the adhesive layer. The adhesive layer can include a silicone coating, other suitable adhesives, or a priming solution that enables the coating to adhere to a metal or polymeric stent (or a stent coating thereon).

[0136] In one or more embodiments, rather than being formed as a tubular structure, the coating can be formed as a strip attached to the outer surface of the stent. For example, the strip may be arranged spirally around the stent, or may be arranged on a circumferential ring, or may be a reverse spiral configuration. In some embodiments, the strip can be applied as a circumferential strip circumferentially attached around at least a portion of the circumference of the stent. In some embodiments, the strip can be a longitudinal strip longitudinally attached to the stent. In some embodiments, the stent can be wound spirally around the stent. In some embodiments, the coating may be applied as a single strip or multiple strips. When the coating is applied as multiple strips, the directly adjacent strips may abut each other or may be spaced apart from each other.

[0137] In at least one embodiment, the strip may be a partial tubular structure that extends along the length of the stent but covers only a portion of the circumference of the stent. In some embodiments, a portion of the stent may be exposed. The adhesive layer can be applied to either at least a portion of the stent or the base of the coating. In at least one embodiment, heat and / or pressure may be applied to ensure proper adhesion of the coating to the stent via the adhesive layer. In at least one embodiment, a discrete micropattern of micropillars can be formed and / or directly attached to either the stent or the polymeric coating.

[0138] In one or more embodiments, the polymeric coating can be dip-coated on the stent without the need for an additional adhesive layer to connect the coating to the stent. It can be formed by casting. For example, the stent can be inserted into a mold including a cavity and a tubular member. The cavity may be defined by the inner wall of the mold that is the reverse of the desired micro-pattern. The stent can be placed on the tubular member such that the inner surface of the stent can be disposed around the tubular member. The mold with the stent can be immersed in a coating material so that the coating material fills the mold and adheres to the stent. In some embodiments, temperature changes and / or pressure changes can be applied to the mold to cure the coating material. When the coating material cures to form a polymer coating, the in vivo prosthesis can be removed from the mold. Alternatively, the polymer coating can be injection molded onto the stent using a similar mold. Instead of immersing the mold in the coating material, the coating material may be injected into the mold.

[0139] In one embodiment, the stent may include an SMP. Examples of SMPs include, but are not limited to, polynorbornene and copolymers of polynorbornene, blends of polyborene and KRATON.RTM. (thermoplastic elastomer) and polyethylene, styrenic block copolymer elastomers (e.g., styrene-butadiene), polymethyl methacrylate (PMMA), polyethylene, polyurethane, polyisoprene, polycaprolactone and copolymers of polycaprolactone, polylactic acid (PLA) and copolymers of polylactic acid, polyglycolic acid (PGA) and copolymers of polyglycolic acid, copolymers of PLA and PGA, polyenes, nylon, polycyclooctene (PCO), polyvinyl acetate (PVAc), polyvinylidene fluoride (PVDF), blends of polyvinyl acetate / polyvinylidene fluoride (PVAc / PVDF), blends of polymethyl methacrylate / polyvinyl acetate / polyvinylidene fluoride (PVAc / PVDF / PMMA) and polyvinyl chloride (PVC), and blends and / or combinations thereof.

[0140] In another alternative manufacturing method, the device may be formed by molding an outer surface modification onto a separate layer of material, such as a nonwoven material. As used herein, the term "nonwoven" and variations thereof can refer to materials formed by casting, molding, spinning, or extrusion techniques, excluding typical textile-forming techniques such as knitting, weaving, braiding, etc. Non-limiting examples of polymeric materials useful for the nonwoven polymer graft portion include, but are not limited to, polyester, polypropylene, polyethylene, polyurethane, polynaphthalene, polytetrafluoroethylene, expanded polytetrafluoroethylene, silicone, as well as combinations and copolymers thereof.

[0141] In some embodiments, the devices disclosed herein can be treated with one or more therapeutic agents. The terms "therapeutic agent", "pharmaceutical", "pharmaceutically active agent", "drug" and other related terms can be used interchangeably herein and can include genetic therapeutic agents, non-genetic therapeutic agents and cells. Therapeutic agents can be used alone or in combination. A wide variety of therapeutic agents can be used in conjunction with the present invention, including those used for the treatment of a wide variety of diseases and conditions (i.e., prevention of a disease or condition, reduction or elimination of symptoms associated with a disease or condition, or substantial or complete elimination of a disease or condition).

[0142] Non-limiting examples of useful therapeutic agents include, but are not limited to, adrenergic agents, corticosteroids, corticosteroid inhibitors, analeptics, aldosterone antagonists, amino acids and proteins, ammonia antidotes, anabolic agents, stimulants, analgesics, androgenic agents, anesthetics, anorectic compounds, anorexics, antagonists, pituitary anterior lobe activators and inhibitors, anthelmintics, antiadrenergic agents, antiallergic agents, antiamoebin agents, antiandrogenic agents, antianemic agents, antianginal agents, anxiolytics, antiarthritis agents, antiasthmatic agents, antiatherosclerotic agents, antibacterial agents, anticholinergic agents, anticoagulants, anticoccidial agents, anticonvulsants, antidepressants, antidiabetic agents, antidiuretics, antidotes, antimovement disorder agents, antiemetics, antiepileptic agents, antiestrogenic agents, antifib Cellulose solvents, antifungal agents, anti-glaucoma agents, anti-hemophilic agents, anti-hemophilic factors, anti-hemorrhagic agents, antihistamines, antihyperlipidemic agents, antihyperlipidemic agents, hypertension medications, hypertension medications, anti-infective agents, anti-inflammatory agents, non-keratinizing agents, antibacterial agents, anti-migraine agents, anti-mitotic agents, antimycotic agents, anti-cancer agents, anti-cancer adjuvants, anti-neutropenia agents, anti-obsessive-compulsive disorder agents, anti-parasitic agents, anti-Parkinson agents, anti-Pneumocystis agents, anti-proliferative agents, anti-benign prostatic hyperplasia agents, anti-protozoal agents, anti-itch agents, anti-psoriatic agents, anti-psychotic agents, anti-rheumatic agents, anti-schistosomiasis agents, anti-seborrheic agents, anti-spasmodics, anti-thrombotic agents, anti-tussives, anti-ulcer agents, anti-urolith agents, anti-viral agents, benign prostatic hyperplasia medications, blood glucose regulators, bone resorption inhibitors, bronchodilators, carbonic anhydrase inhibitors, cardiac depressants, radiation protectors, cardiotonics, cardiovascular agents, cholestatic agents, cholinergic agonists, cholinergic drugs, cholinesterase inactivators, coccidiostat agents, cognitive aids and cognitive enhancers, antihypertensives, diagnostic aids, diuretics, dopamine agonists, ectoparasiticides, emetics, enzyme inhibitors, estrogens, cellulose solvents, free oxygen radical scavengers, gastrointestinal motility agents, glucocorticoids, gonadotropin, hemostatic agents, histamine H2 receptor antagonists, hormones, hypocholesterolemic agents, hypoglycemic agents, lipid-lowering agents, hypotensive agents, HMGCoA reductase inhibitors, immunizing agents, immunomodulators, immunoregulators, immunostimulants, immunosuppressants, impotence therapy adjuvants, keratolytics, LHRH agonists, luteolytics, mucolytics, mucosal protectants, mydriatics, nasal decongestants, nerve relaxants, neuromuscular blockers, neuroprotective agents, NMDA antagonists, non-hormonal steroid derivatives, oxytocin agents, plasminogen activators, platelet-activating factor antagonists, platelet aggregation inhibitors, treatment after stroke and head trauma, progestins, prostaglandins, prostate growth inhibitors, protirelin agents, psychotropic drugs, radioactive agents, resorptive agents, scabicidal agents, sclerosing agents, sedatives, sedative-hypnotics, selective adenosine A1 antagonists, adenosine A2 receptor antagonists, serotonin antagonists, serotonin inhibitors, serotonin receptor antagonists, steroids, stimulants, thyroid hormones, thyroid inhibitors, thyroid mimetics, tranquilizers, unstable angina agents, uricosuric agents, vasoconstrictors, vasodilators, trauma therapeutic agents, wound healing agents, xanthine oxidase inhibitors, etc., and combinations thereof are included.

[0143] Useful non-genetic therapeutic agents for use in connection with the present invention include, but are not limited to, (a) antithrombotic agents such as heparin, heparin derivatives, urokinase, clopidogrel, and dextrorphanylproline arginine chloromethyl ketone; (b) anti-inflammatory agents such as dexamethasone, prednisolone, corticosterone, budesonide, estrogen, sulfasalazine, mesalamine; (c) anti-neoplastic / anti-proliferative / anti-constrictive agents such as paclitaxel, 5-fluorouracil, cisplatin, vinblastine, vincristine, epothilone, endostatin, angiostatin, angiopep, monoclonal antibodies capable of blocking smooth muscle cell proliferation, and thymidine kinase inhibitors; (d) anesthetic agents such as lidocaine, bupivacaine, ropivacaine; (e) anticoagulants such as D-Phe-Pro-Arg chloromethyl ketone, RGD peptide-containing compounds, heparin, hirudin, antithrombin compounds, platelet receptor antagonists, antithrombin antibodies, anti-platelet receptor antibodies, aspirin, prostaglandin inhibitors, platelet inhibitors, and madani antiplatelet peptide; (f) angiogenic cell growth promoters such as growth factors, transcriptional activators, and translational promoters; (g) angiogenic cell growth inhibitors such as growth factor inhibitors, growth factor receptor antagonists, transcriptional repressors, translational repressors, replication inhibitors, inhibitory antibodies, antibodies against growth factors, bifunctional molecules consisting of growth factors and cytotoxins, bifunctional molecules consisting of antibodies and cytotoxins; (h) protein kinase and tyrosine kinase inhibitors (e.g., tyrphostin, genistein, quinoxaline); (i) prostacyclin analogs; (j) cholesterol-lowering agents; (k) angiopoietin; (l) antibacterial agents such as triclosan, cephalosporin, aminoglycoside, and nitrofurantoin; (m) cytotoxic agents, cell growth inhibitors, and cell growth factors; (n) vasodilators; (o) agents that interfere with endogenous vascular mechanisms; (p) inhibitors of leukocyte mobilization such as monoclonal antibodies; (q) cytokines; (r) hormones; (s) HSP including geldanamycin 90 protein (i.e., a molecular chaperone or a housekeeping protein, and Inhibitors of heat shock proteins required for the stability and function of other client proteins / signaling proteins involved in cell growth and survival; (t) Smooth muscle relaxants such as α-receptor antagonists (e.g., doxazosin, tamsulosin, terazosin, prazosin, and alfuzosin), calcium channel blockers (e.g., verapamil, diltiazem, nifedipine, nicardipine, nimodipine, and bepridil), β-receptor agonists (e.g., dobutamine, and salmeterol), β-receptor antagonists (e.g., atenolol, metoprolol, and butoxamine), angiotensin II receptor antagonists (e.g., losartan, valsartan, irbesartan, candesartan, eprosartan, and telmisartan), and antispasmodics / anticholinergics (e.g., oxybutynin chloride, flavoxate, tolterodine, hyoscyamine sulfate, dicyclomine); (u) bARKct inhibitors; (v) Phospholamban inhibitors; (w) Serum 2 gene / protein; (x) Immunomodulators containing aminoquinolines, such as imidazoquinolines (e.g., resiquimod and imiquimod); (y) Human apolipoproteins (e.g., AI, AII, AIII, AIV, AV, etc.); (z) Selective estrogen receptor modulators (SERM) such as raloxifene, lasofoxifene, arzoxifene, miroproxifene, ospemifene, PKS 3741, MF 101, and SR 16234; (aa) PPAR agonists including PPAR-alpha, gamma, and delta agonists such as rosiglitazone, pioglitazone, netoglitazone, fenofibrate, bexarotene, metaglidacen, troglitazone, and tesaglitazar; (bb) Prostaglandin E agonists containing PGE2 agonists such as alprostadil or ONO 8815Ly; (cc) Thrombin receptor activating peptide (TRAP); (dd) Vasopeptidase inhibitors including benazepril, fosinopril, lisinopril, quinapril, ramipril, imidapril, delapril, moexipril, and spirapril; (ee) Thymosin beta4; (ff) Phospholipids including phosphorylcholine, phosphatidylinositol, and phosphatidylcholine; (gg) Containing VLA-4 antagonists and VCAM-1 antagonists.Non-gene therapy agents can be used individually or in combination, including in combination with any of the agents described herein.

[0144] Further examples of non-gene therapy agents, which do not necessarily exclude those listed above, include, inter alia, paclitaxel (in its particulate form, such as protein-bound paclitaxel particles, such as albumin-bound paclitaxel particles, including, for example, ABRAXANE), sirolimus, everolimus, tacrolimus, zotarolimus, Epo D, dexamethasone, estradiol, halofuginone, cilostazol, geldanamycin, alagebrium chloride (ALT-711), ABT-578 (Abbott Laboratories), trapidil, liprostin, actinomycin D, Resten-NG, Ap-17, abciximab, clopidogrel, ridogrel, beta-blockers, bARKct inhibitors, phospholamban inhibitors, Serca 2 gene / protein, imiquimod, human apolipoproteins, growth factors (e.g., VEGF-2), and taxanes such as the aforementioned derivatives.

[0145] Biodegradable polymers that can be used to form the devices disclosed herein, to form at least a part of the devices disclosed herein, or to coat the devices or a part of the devices disclosed herein can include a wide variety of materials. Examples of such materials include, but are not limited to, polyesters, polylactides, polycarbonates, polyanhydrides, poly(amino acids), polyimines, polyphosphazenes, and various naturally occurring biomolecular polymers, as well as their copolymers and derivatives. Certain hydrogels that are crosslinked polymers can also be made biodegradable. These include, but are not necessarily limited to, polyesters, pluronans, poly(amino acids), copoly(ether-esters), polyalkylene oxalates, polyamides, poly(iminocarbonates), polyorthoesters, polyoxaesters, polyamide esters, polyoxaesters containing amide groups, polyanhydrides, polyphosphazenes, poly-alpha-hydroxy Acids, trimethylene carbonate, poly-beta-hydroxy acids, polyorganophosphazenes, polyanhydrides, polyester amides, polyethylene oxides, polyester-ethers, polyphosphoesters, polyphosphoester urethanes, cyanoacrylates, poly(trimethylene carbonate), poly(iminocarbonate), polyalkylene oxalates, polyvinyl pyrrolidone, polyvinyl alcohol, poly-N-(2-hydroxypropyl)-methacrylamide, polyglycols, aliphatic polyesters, poly(orthoesters), poly(ester amides), polyanhydrides, modified polysaccharides and modified proteins are included. Some specific examples of biodegradable materials include poly(ε-caprolactone), poly(dimethyl glycolic acid), poly(hydroxybutyrate), poly(p-dioxanone), polydioxanone, PEO / PLA, poly(lactide-co-glycolide), poly(hydroxybutyrate-co-valerate), poly(glycolic acid-eo-trimethylene carbonate), poly(ε-caprolactone-co-p-dioxanone), poly-L’glutamic acid or poly-L-lysine, polylactic acid, polylactide, polyglycolic acid, polyglycolide, poly(D,L-lactic acid), L-polylactic acid, poly(glycolic acid), polyhydroxyvalerate, cellulose, chitin, dextran, fibrin, casein, fibrinogen, starch, collagen, hyaluronic acid, hydroxyethyl starch and gelatin.

[0146] The above disclosure is illustrative and not intended to be exhaustive. This description suggests many variations and alternatives to those skilled in the art. All of these alternative and variant forms are intended to be included within the scope of the claims where the term "comprising" means "including but not limited to". Those skilled in the art will recognize other equivalents to the specific embodiments described herein, and such equivalents are also intended to be encompassed by the claims.

[0147] Furthermore, the specific features presented in the dependent claims can be combined with each other in other ways within the scope of the present disclosure, as will be recognized such that the present disclosure is also particularly directed to other embodiments having any other possible combination of the features of the dependent claims.

[0148] Accordingly, while particular embodiments of the novel and useful anti-fouling stent of the present invention have been described, such recitations are not intended to be construed as limitations on the scope of the present invention except as set forth in the following claims.

Claims

1. An intravascular prosthesis for placement within a body cavity, comprising a tubular member having an outer surface and an inner surface, the outer surface comprising a first hierarchical microstructure pattern arranged to produce a Wenzel-Cassie state, the inner surface being superhydrophobic or oleophobic and comprising a second microstructure pattern different from the first hierarchical microstructure pattern.

2. The intravascular prosthesis according to claim 1, further comprising a polymer wall, wherein the tubular member is a polymer wall, and the outer surface and the inner surface are located on both sides of the polymer wall, and at least one through hole fluidly connects the outer surface and the inner surface.

3. The intravascular prosthesis according to claim 1, wherein the first hierarchical microstructure pattern comprises a plurality of first microfeatures having a base and a top, and each of the first microfeatures of the plurality of first microfeatures comprises the base having a recurved pillar.

4. The intravascular prosthesis according to claim 3, wherein the first hierarchical microstructure pattern comprises a plurality of second microfeatures arranged around the top of the plurality of first microfeatures.

5. The intravascular prosthesis according to claim 4, wherein the plurality of first microfeatures may have a pitch between adjacent microfeatures of 25 to 100 microns and a height of 10 to 100 microns.

6. The intravascular prosthesis according to claim 1, wherein the second hierarchical microstructure pattern comprises a plurality of microridges, and each microridge of the plurality of microridges has a pitch between adjacent microridges of 100 nm to 10 microns.

7. The intravascular prosthesis according to claim 6, wherein each microridge of the plurality of microridges comprises a length greater than the width.

8. The intravascular prosthesis according to claim 7, wherein the plurality of microridges comprises a subset of microridges, and the height of each adjacent microridge increases gradually.

9. The intravascular prosthesis according to claim 8, wherein the plurality of microridges comprises a second subset of microridges, and the height of each adjacent microridge decreases gradually.

10. The intravascular prosthesis according to claim 9, wherein the first subset of microridges is adjacent to the second subset of microridges.

11. The in-vivo prosthesis according to claim 7, wherein the length of each of the plurality of micro-ridges is arranged coaxially with the central axis of the tubular member.

12. The in-vivo prosthesis according to claim 7, wherein the length of each of the plurality of micro-ridges is arranged circumferentially along the inner surface of the tubular member.

13. The in-vivo prosthesis according to claim 1, wherein the first hierarchical microstructure covers a part of the outer surface.

14. The in-vivo prosthesis according to claim 1, wherein the outer surface comprises a third microstructure pattern different from the first microstructure pattern and configured to transport fluid from a first position to a second position.

15. The in-vivo prosthesis according to claim 14, wherein the third microstructure pattern comprises a plurality of micro-features having a pitch between adjacent micro-features of 5 to 50 microns, a width of 1 to 20 microns, and a height of 5 to 50 microns.

16. The in-vivo prosthesis according to claim 1, wherein the tubular member comprises a first end and a second end, and the first end and the second end flare relative to the central portion of the tubular member.

17. An in-vivo prosthesis for placement within the digestive tract, comprising a tubular member having an outer surface and an inner surface, the outer surface comprising a first hierarchical microstructure pattern that is multifractal, the outer surface further comprising a plurality of pores, the inner surface being superhydrophobic or oleophobic, and comprising a second microstructure pattern different from the first hierarchical microstructure pattern.

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