Anti-scaling support

Abstract

An endoprosthetic device (600) includes a tubular structure having an outer surface and an inner surface such that the inner surface is located in a lumen, and wherein the outer surface includes a pattern of microstructures having graded microstructures that produce an adhesive effect on a target surface. The inner surface comprises a super-hydrophobic or oleophobic microstructure pattern capable of preventing scaling, and the microstructure pattern of the inner surface comprises micro ridges. In addition, the outer surface may include an aperture fluidly connecting the outer surface to the inner surface for delivery of fluid from the target surface interface into the endoprosthesis lumen.

Description

Technical Field

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

[0002] Stents are often used to expand, dilate, or maintain the patency of a narrow body lumen. Stents can be positioned across the narrow area while the stent is in a compressed state. The stent can then be expanded to widen the body lumen. Stents used in the gastrointestinal system are often constructed of plastic or coated wire. Plastic and coated wire stents facilitate retrieval and / or replacement of the stent during follow-up.

[0003] However, plastic stents cannot expand like 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 generally have a diameter of no more than 11.5 Fr (French catheter scale). However, such small diameter stents quickly become blocked in the bile duct and pancreatic duct, requiring replacement every three months or even sooner.

[0004] In the case of coated wire stents, when the stent is deployed, the diameter of the stent is less restricted because such stents can be compressed and then expanded at the delivery site. However, these stents and plastic stents may have problems with fluid leakage around the stent outer surface and migration from their target lumen site. In some cases, fluid accumulation between the stent outer surface and the target lumen surface may be the cause of stent migration, although there are other reasons to cause migration. Devices that can prevent fluid from accumulating between the stent and the target lumen surface can resist the migration of the stent caused by fluid accumulation. Background Art

[0005] The stent of the prior art is designed to fix the drainage stent at the implantation site in the body lumen, including some mechanical mechanisms for keeping the drainage stent in the body lumen. For example, the retention fins protruding radially from the tubular body have been used previously. The retention fins can be formed by forming an inclined slit along the length of the tubular member. Each slit defines a tab and enables the tab to protrude outwardly from the outer surface of the tube to engage the luminal surface of the bile duct to prevent migration. The tabs at the opposite ends of the drainage stent usually extend radially outward toward the middle of the stent. The opening defined by the scraper formed by the tab can provide a path to enter the inside of the stent, where cells or other materials may tend to develop into obstructions, resulting in restrictions on the flow through the stent.

[0006] Drainage stents in the prior art also include one or more curled or coiled end portions. For example, the distal and / or proximal ends of the drainage stent may have a curled configuration, commonly referred to as a "pigtail" configuration. Zimmon's U.S. Patent No. 5,052,998 shows one such example: it discloses an indwelling drainage stent having a fin at one end, a series of drainage perforations along the length of the drainage stent, and a pigtail-shaped configuration at the opposite end. Other stents include fixed fins or pigtail rings located at both ends of the stent. Stents of the prior art are provided with and without drainage perforations as shown in Zimmon's patent.

[0007] Other structures, such as a spiral tubular drain stent with an expandable portion, are disclosed in US2006 / 0167538A1 filed by Rucker on December 21, 2005. A drain stent having one or more curled portions and a drain channel with a lateral opening portion is described in US2006 / 0052879A1 filed by Kolb on August 16, 2005. It should be apparent from the prior art mentioned previously that stent geometry is significantly affected by the need to anchor the stent within a body lumen. Therefore, there is a need to decouple the anchoring mechanism from the stent geometry of a gastrointestinal stent so that the stent can be designed into a more advantageous and effective geometry.

[0008] Furthermore, insertion of a drainage stent placed via endoscopic sphincterotomy may require stretching and cutting of the sphincter of Oddi and surrounding areas, which may impair the function of the sphincter of Oddi after insertion of the drainage stent. In addition to the sphincterotomy procedure used to insert the drainage stent, the location of the bile duct stent placed at the papilla of Vater (e.g., through the sphincter of Oddi) may also result in duodenogastric reflux. A damaged sphincter of Oddi may allow reverse flow of fluid from the duodenum or duodenogastric reflux, leading to bacterial and biofilm deposition and possible obstruction of 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 surrounding areas.

[0009] With particular regard to bile duct stents, drainage devices may be implanted to treat a variety of conditions. For example, a drainage stent configured as a bile duct stent may be implanted in the bile duct to treat obstructive jaundice. Figure 1 is a schematic diagram of a typical bile duct system identifying the right hepatic duct joining with the left hepatic duct to form the common hepatic duct, further identifying the gall bladder and cystic duct, the pancreas and main pancreatic duct, and all of the above joining to form the common bile duct, which opens into the duodenum through the ampulla of Vater and the sphincter of Oddi.

[0010] Figure 2A typical stent placement is shown in the biliary system 200. A stent 201 may be placed in the gastrointestinal tract near the common hepatic duct 206 and the common bile duct 216 where it enters the duodenum 218.

[0011] As a surgical treatment for treating bile duct stricture or obstruction, biliary stent placement is known, wherein a radially expandable biliary stent is implanted into the damaged portion of the bile duct. By performing biliary stent placement, the patency of the damaged portion in the bile duct can be ensured, and as a result, for example, remedy of obstructive jaundice symptoms can be achieved.

[0012] The bile duct stent used in the bile duct stent placement procedure generally has a tubular stent body configured to be expandable and a membrane extending to protrude from one end of the stent body in a cylindrical manner. Conventional bile duct stents are configured so that the membrane extends out toward the duodenum when implanted in the damaged portion of the bile duct. The membrane is configured to allow bile to flow out of the gallbladder to be directed toward the duodenum, and also to prevent reflux from the duodenum to the gallbladder. In this configuration, the function of allowing bile to flow out of the gallbladder to flow to the duodenum and also preventing reflux from the duodenum to the gallbladder is referred to as a "valve function".

[0013] The problems that occur in bile duct obstruction and occlusion are unique to the biliary system due to the harsh environment of the bile drainage system, which is due to pancreatic and biliary enzymes, as well as microorganisms such as fungi and bacteria, which inhabit the bile ducts, making stagnation and damage to these tubes susceptible to complete occlusion by biofilms and organic matter. Therefore, there is a need for a biliary stent with an intraluminal coating that prevents occlusion by these biofilms and organic matter in order to minimize or eliminate complications caused by stent lumen occlusion.

[0014] In addition, ductal bleeding, whether due to stent placement or some other reason, can lead to clot formation and occlusion in and around the stent. Ductal occlusion caused by invasion of tumor within the ductal wall and external compression by tumor mass can be common causes of complications. Therefore, there is a need for a bile duct stent that can have a rigid expanded diameter without applying high normal forces to the body lumen.

[0015] Treatment of ductal occlusion has been partially addressed with stainless steel stents, cobalt-chromium stents, inexpensive plastic stents, and more recently, shape memory alloy stents. However, because these stents are placed in a harsh enzymatic environment, occlusion and reocclusion often occur.

[0016] It is desirable to place a tubular implant such as a stent at the location where the bile duct enters the duodenum. As the bile duct approaches the duodenum, this particular opening widens. As a result, the desired shape of the implant would be a frustoconical shape, but such an implant is inherently prone to migration due to the uneven shape of the stent. Therefore, there is a need for a bile duct stent with a frustoconical profile that also prevents the stent from migrating.

[0017] On the other hand, removable stents are desirable, for example, in applications for treating benign diseases. Some applications of stents include use as a bridge to treatment and less palliative measures, in part due to improvements in some cancer therapies and other methods of treating malignant growths. However, efforts to improve removability are at odds with at least some of the measures taken to reduce the risk of stent migration. An improved stent is needed that reduces trauma during stent removal and improves the adhesion of the stent to the body lumen.

[0018] Therefore, there is a need for an improved stent having, for example, improved resistance to migration, improved adhesion of the stent to the lumen wall, and / or improved removability, while further preventing common problems with prior art devices. Surface textures on stents have not been used in the gastrointestinal tract due to issues with the highly lubricated environment that causes stent migration. However, the surface textures of the present disclosure employ unique surface microstructures that exploit the lubricating aspects of the gastrointestinal lumen to achieve stent anchoring. In some aspects, the surface texture can be configured to create a Wenzel-Cassie interface zone between the stent and the body lumen. Summary of the invention

[0019] The present invention provides an endoprosthesis that can include a polymer coating. In some embodiments, the endoprosthesis can include a plurality of surface features, such as protrusions or textures arranged in a micropattern. As used herein, a micropattern can include a regular or irregular array of microscale features (e.g., protrusions such as micropillars, voids such as textures), which can be layered on the device.

[0020] Hierarchical structures can include microstructures with multiscale morphologies. Recent advances in nanomaterials science have made it increasingly possible to design hierarchical surfaces with specific and tunable properties. Much of this work has focused on hierarchical single-walled carbon nanotube films, which are achieved by a simple, rapid, reproducible and inexpensive aqueous dispersion filtration method. By using this filtration method to vary the thickness of the random network of carbon nanotubes, the wettability of the microstructure can be tailored based on capillary phenomena. This effect can be applied to porous membranes.

[0021] It has also been found that multi-fractal structures, particularly when constructed in a layered surface morphology, can produce a unique two-dimensional extension of the Wenzel and Cassie-Baxter theories of surface wetting. Capillary phenomena in film layered morphologies can produce surprising adhesive properties. For example, the applicant calculated that the difference in surface energy of a microstructured surface and a wet target, considered separately and when in contact, can increase in proportion to the number and size of hydrophilic and hydrophobic regions juxtaposed on the microstructured surface and the target surface. The greater the difference in surface energy between the free surface of the liquid and the contact surface of the solid, a quantitative measure of adhesion can be provided. This difference in surface energy is called barrier energy, or the energy required to destroy the interface with such a structure and allow translation.

[0022] By establishing Wenzel-Cassie zones of hydrophilic regions defined by hydrophilic-hydrophobic boundaries, the long-range order of water can be protected from thermal destruction. In addition, the hydrophobic regions can be used as a backup reservoir 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, because the fluid at the interface between the microstructured surface and the biological tissue is usually a suspension of lipids (hydrophobic) in water (hydrophilic).

[0023] In some embodiments, there may be an ordered hierarchical structure, ranging from microdomains of water and lipids, to exclusion of lipid particles of multi-molecular size, to the ordering of single water molecules, etc. Therefore, it is reasonable to expect that microstructured surfaces that are also hierarchical and ordered in at least two dimensions enhance localization effects that produce high barrier energies.

[0024] The present disclosure may include devices that utilize a liquid interface between an endoprosthesis (e.g., a stent) and a target surface (i.e., the lumen of a tissue) to 1) secure the endoprosthesis to the target surface, 2) create a fluid seal between the endoprosthesis and the target surface, and / or 3) provide an anti-fouling surface that a) resists solid deposition on the endoprosthesis surface, or b) promotes inherently unstable deposition and wicks away in a predictable and expected manner.

[0025] The fixation, sealing and anti-fouling functions of the devices disclosed herein may originate from the surface energy modification of the disclosed surfaces. Hydrophilic-hydrophobic interfaces, such as those formed in the Wenzel-Cassie interface state, may play a more profound role than is generally assumed in the prior art. Solutes in aqueous suspensions are widely excluded from the vicinity of many interfaces, and this exclusion comes from the long-range constraints of water molecules, which nucleate at the interface of the macrostructure surface and protrude well into the aqueous phase, similar to what occurs in liquid crystals. The presence of such unexpectedly large areas of restricted water mobility may affect many features of surface and interface chemistry.

[0026] The present disclosure also relates to a device comprising an adhesive surface with a microstructured surface, wherein the microstructured surface comprises at least two features. In addition, the adhesive surface may include features wherein the lateral aspect ratio of each feature is in the range of from about 0.1 to about 50, and at least one feature size varies by a factor of at least 10%. For example, in one embodiment, there may be two groups of columns. One group of columns has a diameter of 5 microns and a height of 30 microns, while another group of columns has a diameter of at least 15 microns and a height of 75 microns, wherein the first group of columns is disposed on the top surface of the second group of columns. At least two feature dimensions (height, width, and / or length) may be microscopic. In some embodiments, all three feature dimensions (height, width, length) may be microscopic.

[0027] In at least one embodiment, the endoprosthesis optionally has an expanded state and a contracted state, and in some cases may include a stent having a polymer coating attached (e.g., adhered, etc.) to the outer surface of the stent. The stent may have an inner surface defining a lumen. The stent may have an outer surface and a stent thickness defined between the inner surface and the outer surface. The stent may include a plurality of surface textures extending from the stent surface, wherein the textures are arranged in a micropattern. The micropattern may be located on the outer surface and / or the inner surface or both. The micropattern on the outer surface may anchor and / or seal the stent to the target surface. The micropattern on the inner surface may resist scaling. In at least one embodiment, the stent may be a flared stent. Optionally, the stent may include surface features for fluid transport, wherein the fluid is conducted from the space between the outer surface of the prosthesis and the target lumen surface, or may include a fluid transport device, wherein the fluid may be transported to the lumen of the stent. The latter may be achieved by a through hole, which may generate a flow gradient due to capillary action. In some embodiments, the through hole may have a uniform channel, such as a cylinder. In some embodiments, the through hole may be conical, or may be truncated conical.

[0028] In one or more embodiments, the stent may include a base and a tissue engaging portion. The base may include a first surface (e.g., an outer surface to which the stent is attached or includes). The tissue engaging portion may include a second surface facing outward from the stent. The tissue engaging portion may include a structure defining a plurality of protrusions or pits 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 be connected. In one or more embodiments, the base may cover any hole of the stent. When the endoprosthesis is expanded in a lumen defined by the vessel wall or is in an implant configuration, the structure defining a plurality of surface textures may generate an adhesion force capable of generating an interlock between the vessel wall and the endoprosthesis. The interlock may be fixed and / or fluid-tight.

[0029] In one or more embodiments, the stent surface may include a plurality of protrusions (e.g., micropillars) of at least two scale sizes extending from the base (e.g., outward from the stent) and arranged in layers. In one or more embodiments, the protrusions may be arranged in a regular micropattern (e.g., micropillars). The outer surface microstructure can 1) generate axial shear forces to inhibit axial migration of the stent, or 2) generate radial normal forces to attract the target lumen surface to the outer surface of the stent to generate a sealing means, or both.

[0030] In one or more embodiments, the fixation and sealing capabilities can be combined or combined to introduce a locking capability of the device to a target surface, where the external microstructure of the device changes size due to the absorption of fluid when placed in a target lumen, and such fluid absorption causes the size of the microstructure to change and produce a grasping action. For example, the microstructure posts can expand to capture tissue disposed in the gaps between the posts.

[0031] In one or more embodiments, the surface of the stent may include a plurality of fluid conducting 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 the fluid from the space between the outer surface of the stent and the target surface. Alternatively, the fluid can be radially transported from the interface volume to the lumen of the stent through holes in the stent wall. The latter fluid transport feature can be used in bile duct stents because such stents typically span bifurcations of tissue lumens, where it is desirable to allow the cross lumen to drain into the lumen of the stent.

[0032] In one or more embodiments, the stent surface may include a plurality of protrusions of at least one dimension extending from a base inwardly toward the lumen of the stent that effectively present an anti-fouling surface capable of preventing accumulation of fluid components conducted through the lumen of the stent.

[0033] In one or more embodiments, the surface of the stent may include a plurality of protrusions of at least one dimension extending from the base inwardly toward the lumen of the stent, which may provide a surface that promotes deposition of a certain morphological type. For example, the microstructures may be arranged as rounded islands that can promote discontinuous deposition that easily fall off as particles.

[0034] Alternatively, a resorbable surface coating on the microstructures may provide for shedding of the deposited layer.

[0035] Although not wishing to be bound by theory, the target tissue may be bonded to the micropatterned surface or coating by one or more non-mechanical mechanisms. As disclosed herein, in some embodiments of the present disclosure, non-abrasive bonding may be achieved by creating one or more interface structures such as, but not limited to, 1) Wenzel-Cassie, 2) capillary, and / or 3) intrinsic mode or Schallamach.

[0036] In some embodiments, the target tissue can interlock with a micropatterned coating having one or more microstructures by tissue invasion around and / or between one or more micropillars. In at least one embodiment, the tissue grasping mechanism can cause the tissue to engage and / or interlock with a micropatterned coating having a structure defining one or more textures (e.g., voids, negative spaces, etc.) or a network of connected textures, wherein tissue and / or cell ingrowth occurs within the textures.

[0037] In one or more embodiments, a van der Waals adhesion mechanism can be formed between tissues in contact with the micropatterned coating, which can include, for example, a mucoadhesive gel.

[0038] In one or more embodiments, the joining of tissue to a micropattern having an appropriate geometry can be performed by proximity attraction of van der Waals bonds. Herein, "interlocking" can be understood to mean: joining of a microstructure having micropillars and / or micropores to a target tissue via any one or more mechanisms described herein or otherwise known to those skilled in the art (e.g., tissue ingrowth, chemical bonding, proximity attraction, etc.).

[0039] However, some embodiments of the present disclosure may not rely on tissue engagement via gripping or friction. In fact, the initial tissue engagement mechanism can position the tissue to the device through the surface energy properties of the microstructures of the present specification. The surface energy interactions that can be mediated by capillary bridges can be characteristically non-destructive and reversible, so that the stent can be removed from the body lumen without damaging the intraluminal tissue.

[0040] Applicants have surprisingly found that surface structures including hydrophilic and hydrophobic domains juxtaposed laterally or in a stacked manner can attract or repel different in vivo fluids and solid components. For example, hydrophilic regions of the surface texture can associate with hydrophilic tissue components, while hydrophobic regions of the surface texture can associate with hydrophobic components. During this association, the interfacial energy may be reduced, resulting in scaffold-tissue adhesion. The destruction of this adhesion state may require energy consumption, and therefore the Wenzel-Cassie association may be stable to dislocation. Even if micro-dislocation occurs, the Wenzel-Cassie state can be quickly reconstructed.

[0041] It can be appreciated that in some embodiments, van der Waals forces can be involved in the formation of Wenzel-Cassie adhesion zones, but they do not result in protein denaturation, which can be understood to characterize the general binding mechanism disclosed herein. In Wenzel-Cassie interaction zones, hydrophilic and hydrophobic regions can be interlocked, and displacement of the scaffold may require mixing of these zones, which may require energy input.

[0042] In a second unexpected aspect, applicants have discovered that capillary action can play a role in stabilizing the Wenzel-Cassie zones and providing an initial mechanical aspect that can draw the stent and lumen surfaces together. For example, pits or through-holes disposed on the stent surface can exploit the difference in surface tension between the hydrophilic and hydrophobic domains, as well as the surface energy of the substrate material, to transport liquid during the formation of the stent-lumen interface. For example, if the lumen surface contains a liquid, the surface texture of the stent can be configured to induce capillary domains to draw the fluid away from the stent-lumen interface.

[0043] It should be appreciated that the hydrophilic / hydrophobic conditions can be induced on the surface 1) chemically or based on molecular structure, and / or 2) texturally, induced by the geometry and hierarchical arrangement of microstructures. The hydrophobicity of both surface types can generally be characterized by surface energy.

[0044] Finally, the applicant has found that the target surface can show a characteristic spatial frequency response. This property of material can be referred to as the eigenmode response of the surface. In the present application, the eigenmode response can be to induce surface wrinkles in the target surface with a characteristic spatial frequency. The spatial frequency of the textured surface of the support is matched with the eigenmode of the luminal surface and the adhesive interface can be basically stabilized. In particular, on several spatial eigenmode frequencies of the target surface, the spatial frequency of the textured surface is matched by the hierarchical arrangement of the surface texture and multiple interface regions can be formed in the energy minimum zone. The energy required to destroy these energies is minimized, and therefore the support can be stabilized to prevent migration, and there will be no undesirable force acting on the tissue surface (such as those forces that cause inflammation, cell death or cell damage).

[0045] It should be appreciated that the Wenzel-Cassie interface can be considered as a multidimensional low energy state that juxtaposes attractive and repulsive forces. Due to various factors, the surface domain can be attractive and / or repulsive. These factors may include, but are not limited to, the ion content of the interface layer, the degree of order or disorder in the material containing the surface pattern, and various chemical treatments of the surface. Therefore, as used herein, the Wenzel-Cassie interface may include any interface that forms an attraction and repulsion region between the textured surface and the target surface in a low energy state. The difference between the energy state of the interface and the energy state of the textured surface and the target surface in separation may be linearly proportional to the shear adhesion strength. In order to achieve high peeling force (normal force adhesion), a capillary aspect may be adopted in the surface pattern design.

[0046] As disclosed herein, the combination of the above findings can produce bonded textured surfaces that can be optimized for a variety of target surfaces. A skilled artisan in the field of solid state physics can measure the energy difference between the separated and joined states of the textured surface and the target surface to consider how to design certain surfaces disclosed herein.

[0047] In addition to any adhesive properties of the devices disclosed herein, a repellent surface may be desired to prevent fouling of the stent after deployment into a tissue lumen. Such a surface may employ a global hydrophobic surface or a zoned hydrophobic surface, wherein alternating regions of hydrophobicity and hydrophilicity can prevent biofilm formation and / or migration of fungi or bacteria. In one embodiment, the interior surface of the stent may be a conditioned hydrophobic / hydrophobic surface, and the exterior surface may be a conditioned hydrophobic / hydrophilic surface, wherein each surface may be described as a hierarchical patterned surface designed for a specific biological interface.

[0048] The micropattern can be specifically designed for a specific tissue to effectively position the stent to the target tissue. In at least one embodiment, the micropattern can be present along at least a portion of the endoprosthesis. In at least one embodiment, the texture of the micropattern can be uniform, or the micropattern can be formed by a texture having a first configuration and a texture having a second configuration.

[0049] The shapes of at least some of the plurality of textures may be selected from cylinders, rectangular prisms, polygonal prisms, spheres, spheroids, ellipsoids, and the like. Some textures may be continuous and selected from sinusoidal height variations (waves), ridges, concentric structures, and the like.

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

[0051] In at least one embodiment, each texture of the micropattern has a first size and a second size, wherein the first size can be between about 1 micron and 1,000 microns (e.g., between about 1 micron and 1,000 microns), wherein the second size can be between about 1 micron and 1,000 microns (e.g., between about 10 microns and 1,50 microns), and one of the textures can be completely disposed on top of the other texture, wherein the ratio between the pitch of the first texture and the pitch of the second texture can be between about 0.1 and 0.5. In at least one embodiment, each protrusion has a ratio between the first size and the second size that can be between about 0.2 and 0.3.

[0052] In at least one embodiment, the endoprosthesis can be retrieved by, for example, a retrieval loop at the distal end of the stent.

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

[0054] Several methods of manufacturing embodiments of an endoprosthesis are known in the art. One method of manufacturing includes forming a polymer coating, wherein the polymer coating includes a substrate and a tissue engaging portion. The substrate includes a first surface. The tissue engaging portion includes a second surface facing away from the first surface and includes a structure defining a plurality of textures extending inwardly or outwardly from the second surface toward the substrate. In one or more embodiments, the textures are arranged in a micropattern. The method also includes: providing a stent having an inner surface and an outer surface defining a lumen; and attaching the substrate 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 textured micropattern can be prepared using photolithography, salt leaching, electrospinning and / or laser ablation. In some embodiments of micropatterns including micropillars, the polymer coating can be formed by using an inverted mold with a micropattern and injecting a polymer material into the mold, and in some cases applying temperature or pressure to the mold before the polymer material is cured, using soft lithography, or by etching the polymer coating from a layer of polymer material. In at least one embodiment, an adhesive layer is applied to at least one of the surface of the substrate and the outer surface of the stent. In at least one embodiment, the polymer coating is formed into a tubular structure. In one or more embodiments, the polymer coating is formed into a strip that is wound around the outer surface of the stent (e.g., spirally wound, circumferentially wound, randomly wound, etc.).

[0056] In at least one or more embodiments, a polymer coating is provided on the stent to allow a portion of the stent to move relative to the target tissue. This feature is particularly important when the target lumen produces peristaltic motion. A combination of "slip" and "adhesion" features of appropriate spatial frequencies can allow the stent to transmit peristaltic motion without being displaced by such motion. For example, circumferential rings of textured surfaces can be placed 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 placed at 1 / 3 of the spatial frequency. Alternatively, one end of the stent can have no surface texture and the other end has a surface texture so that the compressive pressure between the two ends is eliminated by sliding of one end.

[0057] The present disclosure may include embodiments including textured surface stent devices that may allow for adequate anchoring while reducing the risk of migration, reducing fluid accumulation between the stent exterior surface and the target lumen, and otherwise providing an internal microstructured surface that inhibits surface fouling.

[0058] The present disclosure may include embodiments that include a stent that is adapted to resist migration within a body lumen and to conform to a tortuous installation path or installation location. The stent may include a first segment that is generally self-expandable, has a predetermined compressibility, and is adapted to allow the segment to conform to the shape of the body lumen through which it is transported or to surround the segment when deployed. The stent may also include a second segment that is free to move within the target lumen.

[0059] Intraluminal stent grafts can include one or more healing promoter sections, which are attached in the proximal anchoring region of the intraluminal stent graft, and are optionally attached in one or more distal anchoring regions. The healing promoter can be a chemical arranged in an absorbable layer, or is simply a second textured surface designed to guide the ingrowth of cells of a particular type. The healing promoter can be a tissue scaffold. When the intraluminal stent graft is positioned in the lumen, the healing promoter section promotes and guides migration, proliferation and adhesion of vascular cells and intraluminal stent grafts to increase local healing. Therefore, the healing time after the intraluminal stent graft is implanted can be reduced, and a more stable implant is produced, which is less prone to migration and / or internal leakage (otherwise it may be formed at the side of the proximal neck). BRIEF DESCRIPTION OF THE DRAWINGS

[0060] Figure 1 The typical bile duct system is illustrated.

[0061] Figure 2 is an illustration of a typical stent placement in the biliary system.

[0062] Figure 3 is a cross-sectional view of one embodiment of a gastrointestinal endoprosthesis of the present disclosure.

[0063] Figure 4 The anti-fouling microstructure is shown.

[0064] Figure 5 shows an isometric view of the anti-fouling microstructure.

[0065] Figure 6 The gastrointestinal endoprosthesis stent of the present invention having a fluid conducting device and a shedding mechanism is shown.

[0066] Figure 7 The anti-fouling microstructure of the present invention is shown. DETAILED DESCRIPTION

[0067] The following detailed description and accompanying drawings describe and illustrate various exemplary embodiments of the present invention. These descriptions and accompanying drawings are used to enable those skilled in the art to make and use the present invention. Although the present invention will be described with reference to preferred embodiments, those skilled in the art will recognize that changes can be made in form and detail without departing from the spirit and scope of the present invention. Therefore, the following detailed description is intended to be considered illustrative rather than restrictive, and it is the appended claims, including all equivalents thereof, which are intended to limit the scope of the present invention.

[0068] The term "proximal" as used herein is a broad term and is to be given its ordinary and customary meaning to those skilled in the art and is not limited to referring generally in the direction toward the physician during medical procedures.

[0069] The term "distal" as used herein is a broad term and is to be given its ordinary and customary meaning to those skilled in the art and is not limited to referring generally to a direction toward a target site within a patient's anatomy during a medical procedure.

[0070] As used herein, the terms "comprises," "including," "having," "having," "containing," and variations thereof are broad terms and are to be given their ordinary and customary meanings to those skilled in the art and are intended to be open transitional phrases, terms, or words that do not exclude the possibility of additional actions or structures.

[0071] The term "body lumen" as used herein is a broad term and is to be given its ordinary and customary meaning to those skilled in the art and is not limited to referring to the lumen of body passages that conduct fluids, including but not limited to the gastrointestinal tract, bile ducts, pancreatic ducts, ureteral passages, esophagus, and blood vessels (such as those of the human vasculature).

[0072] The term "implantable" as used herein is a broad term and will be given its ordinary and customary meaning to those skilled in the art, and refers to, but is not limited to, the ability of a medical device to be positioned at a location within the body, such as within a body lumen. In addition, the terms "implant" and "implanted" as used herein are broad terms and will be given their ordinary and customary meaning to those skilled in the art, and are not limited to referring to positioning a medical device at a location within the body, such as within a body lumen.

[0073] The terms "intraluminal," "intraluminal," and "transluminal" as used herein are broad terms and are to be given their ordinary and customary meanings to those skilled in the art and are not limited to referring to an implantation procedure in which a medical device is advanced from a distal location within a body lumen and through the body lumen to a target site within the body lumen. Intraluminal delivery may include implantation into the bile duct from an endoscope or catheter.

[0074] The term "expandable mesh" as used herein is a broad term and will be given its ordinary and customary meaning to those skilled in the art, and is not limited to referring to a self-expanding and / or non-self-expanding structure made of any generally rigid or elastic material, which has an open network or arrangement when expanded, otherwise it will allow tissue to grow inward, and otherwise it will not prevent fluid from flowing through its wall. Several prior art mesh stents have been used with polymer sheaths or coverings; however, these sheaths must be stretched to increase size. These materials apply a force that resists expansion, which tends to limit the final expansion size of the prior art mesh. In addition, this resistance may make the expansion of the mesh more problematic. Alternatively, when the prior art mesh is compressed, the sheath can be folded or bundled on the prior art mesh so that no force is applied when expanded. However, this method increases the overall size of the compressed prior art stent, so that a larger size catheter is required for a given size of stent.

[0075] The term "layering" as used herein is a broad term and will be given its ordinary and customary meaning to those skilled in the art, and is not limited to referring to microstructures having larger and smaller sizes relative to each other in at least one aspect, that is, larger-sized microstructures and smaller-sized microstructures. In some examples, larger-sized microstructures can support smaller-sized microstructures. Generally, micron-scale features will be understood to include structures having dimensions (e.g., length, width, height, pitch, and / or slope) ranging from about 1 micron to about 10,000 microns. In this article, unless the context indicates otherwise, micron-scale features may be collectively referred to as surface textures.

[0076] The term "tissue adhesive" as used herein is a broad term and will be given its ordinary and customary meaning to those skilled in the art and is not limited to referring to a surface comprising a layered micropattern that can resist translation in directions normal to and / or parallel to the target surface when in contact with a target surface. As an example, a device that acts as a tissue adhesive can generate peel forces and / or shear forces when placed in contact with a target surface and subjected to some external force.

[0077] The term "cell promoter" as used herein is a broad term and will be given its ordinary and customary meaning to those skilled in the art, and refers to, but is not limited to, a surface that can direct cells in a particular direction, and / or promote a certain type of cell to populate a surface, and / or direct certain cell combinations to populate a surface, and / or promote certain cell types while blocking other cell types. In one example, a cell promoter can cause tissue adjacent to the cell promoter surface to heal faster and with greater strength than some other tissue not adjacent to the cell promoter.

[0078] The term "anti-fouling surface" is a broad term and will be given its ordinary and customary meaning to those skilled in the art and refers to, but is not limited to, a surface that resists the accumulation of molecules, particles or cells. As an example, an anti-fouling surface can be a surface that inhibits the accumulation of substances from the environment in which the surface is placed.

[0079] The term "Wenzel interface" is a broad term and will be given its ordinary and customary meaning to those skilled in the art and refers to, but is not limited to, a surface having a surface texture comprised of a plurality of surface features that can absorb water between the surface features of the surface texture when in contact with a wet target surface.

[0080] The term "Cassie interface" is a broad term and will be given its ordinary and customary meaning to those skilled in the art and refers to, but is not limited to, a surface having a surface texture comprised of a plurality of surface features that, when in contact with a wet target surface, prevent water from interpenetrating between the surface features of the surface texture.

[0081] The terms "eigenmode," "wrinkle eigenmode," and "wrinkle pattern" are broad terms and will be given their ordinary and customary meaning to those skilled in the art, and refer to, but are not limited to, the natural wrinkling of a tissue surface when exposed to shear forces. Tissue eigenmodes are well defined and characterized by the bending modulus of the tissue. A given tissue type may naturally wrinkle, or develop spatial periodicities that are characterized by a spectrum of these spatial periodicities.

[0082] The terms "Schakkamach waves" and "Schakkamach wrinkles" are broad terms and will be given their ordinary and customary meaning to those skilled in the art and refer to, but are not limited to, the occurrence of separation waves known to occur during wear experiments of target substrates. In some examples, Schakkamach waves are explained in terms of elastic instabilities of elastomeric surfaces. For example, if the surface of a device is designed to anticipate these waves by adopting a surface periodic structure whose spatial frequency may be slightly lower than the expected Schakkamach waves, such Schallamach waves may be captured into the periodic structure and significantly increase the shear force required for translation. This "Schallamach matching" design may reduce friction damage between the device surface and the target surface.

[0083] The term "micropattern" or "microstructure" is a broad term and will be given its ordinary and customary meaning to those skilled in the art and refers to, but is not limited to, regular or irregular patterned textures (e.g., stent textures) in which the shortest center-to-center distance (i.e., the distance between geometric centers, the pitch) of adjacent textures (i.e., textures that share an edge) is greater than 1 micron. In a regular pattern of textures, each of the two geometric centers is equidistant from an edge shared by adjacent textures. In an irregular pattern of textures, the two geometric centers are not equidistant from an edge shared by adjacent textures. In an irregular pattern of textures, the spacing parameter may satisfy an average value, such as an average distance between microstructure centers.

[0084] The words connected, coupled, and communicated refer to any form of interaction between two or more entities, including mechanical, electrical, chemical, magnetic, electromagnetic, fluid, 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 through an intermediate component.

[0085] Disclosed herein are a variety of medical devices for implantation in a body lumen. Some embodiments relate to a medical drainage device comprising two or more planar curvilinear bends in a tubular member, wherein each bend can bend in opposite directions relative to an adjacent bend. For example, a pair of continuous planar curvilinear bends can form a pigtail or spiral configuration. In some embodiments, the curvilinear bend can define a tortuous portion of a drainage lumen within the tubular member.

[0086] The medical drainage devices disclosed herein may be described with respect to exemplary bile duct stent embodiments including a tubular support member. However, embodiments of bile duct drainage stents may also illustrate other drainage devices, such as drainage catheters, ureteral stents, or esophageal stents provided according to other embodiments. For example, the drainage stent may be configured for use in the ureter, urethra, esophagus, or blood vessels.

[0087] Although the subject matter of the present disclosure can be implemented in many different forms, various embodiments of the present disclosure are described in detail herein. This description is an example of the principles of the present disclosure and is not intended to limit the present disclosure to the specific embodiments described.

[0088] For purposes of this disclosure, like reference numerals in the drawings refer to like features unless otherwise indicated.

[0089] In some embodiments, the present disclosure relates to micropatterned polymer coatings or surfaces for medical devices. In some embodiments, micropatterned polymer surfaces can be used for implantable medical devices, such as stents, to reduce or prevent stent migration, particularly stents for gastroesophageal systems, including but not limited to esophageal stents, bile duct stents, and colon stents. In one or more embodiments, the micropatterned polymer coating may include microscale textures at regular or irregular intervals. In one or more embodiments, the micropatterned polymer coating may include microscale textures (e.g., gaps, spaces, channels, passages, etc.) of regular or irregular shapes. In one or more embodiments, the micropatterned polymer coating may include microscale textures of regular or irregular intervals and shapes. In some embodiments, such microscale textures may promote, for example, controlled cell migration and tissue ingrowth.

[0090] The microstructures of the present invention are capable of generating forces due to: 1) affinity / repellency effects, 2) microtopology, 3) absorption chemistry, 4) morphological expansion, and / or 5) active mechanical interactions. These forces can be generated in dry conditions, wet conditions, moist conditions, or a combination thereof.

[0091] In some embodiments, the devices of the present disclosure may include anti-fouling aspects, wherein microstructures exhibiting oleophobic properties on the inner surface of the support may contribute to the anti-fouling properties. In some embodiments, the anti-fouling surface may include pores that can attract a water film, thereby creating an ultra-nano hydrophilic structure to form a protective layer that can exhibit anti-fouling properties.

[0092] In addition to antifouling properties, some devices may be able to produce similar self-cleaning effects. Self-cleaning strategies do not necessarily inhibit deposition, but can present surface topography similar to shark skin or butterfly wing microstructures, which are known to cause accumulated materials to be easily released from the microstructured surface.

[0093] In some embodiments, micropatterned surfaces can be modified with zwitterionic polymer brushes or with polyelectrolyte multilayers to enhance their antifouling and / or self-cleaning properties. Additionally, in some embodiments, antifouling properties can be combined with fluid transport functions. For example, a surface with micro-ridged morphology can exhibit both fluid transport and antifouling properties.

[0094] In some embodiments, anti-fouling can be associated with drag-reducing microstructured surfaces. For example, shark skin morphology is known to have anti-fouling properties. One interesting aspect of shark skin microstructures in relation to anti-fouling capabilities is their ability to promote laminar flow. Turbulence across the surface is understood to cause fouling due to re-entrant fluid loops that can roll along the interfacial surface. Some microstructured surfaces can produce a fluid dynamic lift effect similar to the aerodynamic flow of air over an airplane wing. Although in the example of an airplane wing the fluid cannot expand like a gas, the lifting effect of the microstructure can push nucleated particles away from the surface, thereby creating a particle-free fluid zone.

[0095] In a preferred embodiment, the stent includes the following regions: 1) a region that adheres directly to the target lumen, 2) a region that seals to the target lumen, 3) a region for fluid transport, and / or 4) a region that resists fouling.

[0096] Embodiments of the endoprosthesis disclosed herein are Figure 3 , which has a lateral cross-sectional view of the endoprosthesis. Figure 3 , the endoprosthesis 300 may include a polymer wall 306. In one or more embodiments, the endoprosthesis 300 may be a preformed stent. In some embodiments of the present disclosure, the endoprosthesis 300 may include a tubular member 308, which may have at least a portion including a constant diameter, may include one or more tapers, or one or more flares, and / or other variations in diameter in the tubular member 308 and / or at one or more ends 309, 310. Figure 3 The endoprosthesis 300 shown in FIG. 3 may include an inner surface 312 and an outer surface 314 of a polymer wall 306. The outer surface 314 may include one or more microstructure patterns disposed about the surface. In some embodiments, the layered microstructure pattern 320 of the present invention on the outer surface 314 may cover only a portion of the outer surface. In some embodiments, the layered microstructure pattern 320 may cover 1 to 100% of the outer surface 314. In some embodiments, the layered microstructure pattern 320 may 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, the layered microstructure pattern 320 may 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. Figure 3 As shown in, the outer surface 314 may include a plurality of microstructure patterns disposed around the surface such that the surface is covered by the plurality of patterns by 1% to 100%. It will be readily appreciated that the percentage of each microstructure pattern disposed around the outer surface 314 may be within the above percentages, totaling 100% or less.

[0097] In some embodiments, the microstructure pattern 320 of the outer surface 314 may include hierarchical microfeatures 321, wherein smaller microfeatures 323 are disposed around larger microfeatures 325. In some embodiments, the microstructure pattern 320 may include hierarchical microfeatures 323, 325, wherein larger microfeatures 325 include recurved pillars 322. In some embodiments, the recurved pillars 322 may include T-shaped structures 324 at their top sections. In some embodiments, the recurved pillars 322 may include smaller pillars 326 disposed thereon. In some embodiments, the smaller pillars 326 may be disposed around the top surface of the recurved pillars 322. In some embodiments, the recurved pillars 322 may be arranged in a triangular pattern relative to adjacent pillars. The recurved pillars 322 may be arranged such that the spacing or interval between adjacent pillars may be from 1 to 500 microns, from 1 to 250 microns, from 25 to 250 microns, or from 25 to 100 microns. In some embodiments, the inner curved posts 322 may have a diameter of from 1 to 500 microns, from 1 to 250 microns, from 1 to 100 microns, from 1 to 50 microns, or from 10 to 50 microns. In some embodiments, the inner curved posts 322 may have a height of from 1 to 500 microns, from 1 to 250 microns, from 1 to 100 microns, from 1 to 50 microns, or from 10 to 100 microns. In some embodiments, the inner curved posts 322 may have a pitch or spacing between adjacent posts of from 25 to 100 microns, a diameter of from 10 to 50 microns, and a height of from 10 to 100 microns. For embodiments in which the inner curved posts 322 include a T-shaped top configuration, the top portion of the T-shaped configuration may be circular with a diameter 1.2-2.5 times the diameter of the base portion of the inner curved posts.

[0098] In some embodiments, the second pillars 326 disposed around the inner curved pillar 322 have a spacing between adjacent pillars of from 10 to 50 microns, a diameter of from 10 to 150 microns, and a height of from 1 to 10 microns. In some embodiments, these second pillars 326 can be made of a liquid swellable polymer.

[0099] In some embodiments, the target tissue can be held between the large microfeatures 322, 325. In some embodiments, the tissue can be held between the T-shaped structures 324 of the inner curved posts 322. In some embodiments, the T-shaped structures 324 can have swelling properties that can provide a clamping action on or around the tissue 328, whether contacting or non-contacting.

[0100] In at least one embodiment of the present disclosure, outer surface 314 may include a microstructure pattern for transporting fluids.

[0101] like Figure 3As shown in FIG. 1 , the inner surface 312 may include a microstructured pattern 330 including microridges 334 that may be made of microfeatures having a ridge-like shape. In some embodiments, the microridges 334 may include a wing-like profile in which the ends have a tapered shape and the center portion is higher than the end portions. The microstructured pattern 330 may include a plurality of microfeatures of microridges 334 that may be spaced from 1 nm to 100 microns, from 10 nm to 50 microns, or from 100 nm to 10 microns with their edges separated between adjacent features (see FIG. 1 ). Figure 4 To obtain additional illustration, micro ridges 434). Figure 4 As shown in , in some embodiments, the micro-ridges 434 may have a length in the axial dimension 442 that may be longer than the width 444 of the micro-ridges 434. In some embodiments, the ridges 334, 434 may form groups 340, 440 or islands, where the individual micro-features may be considered a first microstructural level and the groups or island shapes 340, 440 may be considered a second microstructural level. It is contemplated that the two microstructural levels work together to promote laminar flow through the stent lumen.

[0102] In some embodiments, the microstructured pattern 320 of the outer surface 314 may include microfeatures in the form of microridges 318 for fluid conduction properties. The microridges 318 may have a pitch of from 1 to 500 microns, from 1 to 250 microns, from 1 to 100 microns, from 1 to 50 microns, or from 5 to 50 microns. The microridges 318 may include a width of from 1 to 100 microns, from 1 to 50 microns, from 1 to 40 microns, from 1 to 30 microns, or from 1 to 20 microns. The microridges 318 may include a height of from 1 to 500 microns, from 1 to 250 microns, from 1 to 100 microns, from 1 to 50 microns, or from 5 to 50 microns. Reference Figure 3A The micro-ridges 318 can be arranged such that the lengths of the micro-ridges 318 are positioned in a circumferential pattern relative to the central axis 350 of the endoprosthesis (i.e., Figure 3A ), or the micro-ridges 318 may be arranged such that the length of the micro-ridges is axially positioned relative to the central axis of the endoprosthesis (i.e., on the "y" axis shown in FIG. Figure 3A ). The plurality of micro-ridges 318 may be parallel, converging, or bifurcating. In some embodiments, the bifurcations of the micro-ridges may be directed toward the ends of the stent to draw fluid away from the interface volume defined by the outer wall of the stent and the surface of the target lumen.

[0103] In at least one embodiment, Figure 4As shown in , the inner surface 412 may include at least one pattern of micro-ridges 434. In some embodiments, the inner surface 412 may include a second pattern of micro-ridges, which may include additional multiple micro-ridges. As described above, but shown in a different manner, in some embodiments, the length dimension 442 of the micro-ridges 434 can be oriented in an axial position relative to the central axis of the endoprosthesis. In some embodiments, the length 442 of the micro-ridges 434 can be oriented in a circumferential pattern relative to the central axis of the endoprosthesis. In other embodiments having multiple micro-ridges 434, a first portion of the multiple micro-ridges can be oriented in an axial configuration relative to the central axis of the endoprosthesis, and a second portion of the multiple micro-ridges can be oriented in a circumferential configuration relative to the central axis of the endoprosthesis. The micro-ridges 434 can have an airfoil profile that can guide particles away from the support substrate surface 412.

[0104] Referring now to FIG. 5 , in some embodiments, the microstructure pattern 530 of the inner surface may be arranged in a sinusoidal distribution 502 relative to the length and / or height of the variation of the microfeatures (shown in FIG. 5 ). The groupings of microstructures 540 or islands as described above may be composed of microridges 534, wherein the groupings or islands 540 may be considered as a first microstructure level and the microridges 534 may be considered as a second microstructure level. The sinusoidal arrangement 502 is shown as an illustrative reference in the “bird's eye view” and “side view” of FIG. 5 . The center positions 512 of the individual microridges 534 may be equally spaced in various geometric patterns, such as a square grid pattern or a triangular pattern. In addition, the microridges 534 may be arranged in a uniform array or a non-uniform array. In addition, the groupings or islands 540 may be arranged in a similar manner, wherein the groupings are arranged in a geometric pattern (e.g., a square or grid pattern) or in a uniform or non-uniform pattern relative to each other. Additionally, with reference to both individual microridges 534 and groupings / islands 540, one subset may be arranged geometrically, either uniformly or non-uniformly, while another subset may be arranged differently, and so on for other subsets.

[0105] Reference now Figure 6 , shows an embodiment including a longitudinal cross-sectional view of an endoprosthesis device 600 having a substrate 602 including an outer surface and an inner surface, wherein the outer surface includes an outer sealing microstructure 604. Figure 6, the endoprosthesis 600 may have a first end 601 and a second end 603. In some embodiments, the outer sealing microstructure 604 may be layered, having at least a first microstructure disposed in a layered manner around a second microstructure, as disclosed elsewhere herein. In some embodiments, the endoprosthesis device 600 may also include an anti-migration microstructure pattern 606. In some embodiments, the device 600 may include a flared end 608. In some embodiments, the device 600 may include anti-fouling microstructure patterns 610 and 612 disposed around an inner surface 611. In some embodiments, the endoprosthesis device 600 may include a fluid conducting microstructure pattern 614. In other embodiments, the endoprosthesis device 600 may 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 may include any combination of the aforementioned microstructure configurations.

[0106] like Figure 6 , the outer surface 616 of the flared end 608 may be smooth or may be decorated with a microstructure pattern 618. In some embodiments, the outer microstructure pattern 604 may include a sealing configuration, such as the sealing microstructure 604 described previously, and may be composed of a first pillar 620 having a diameter of from 10 to 100 microns, a pitch of from 20 to 200 microns, and a height of from 10 to 100 microns. In some embodiments, the sealing microstructure may also include a second pillar 622 disposed around the first pillar 620, wherein the second pillar may include a diameter of from 1 to 10 microns, a pitch of from 2 to 20 microns, and a height of from 1 to 10 microns.

[0107] In some embodiments of the device 600 including the anti-migration microstructure pattern 606, the microstructure pattern may include a first two-dimensional sinusoidal microstructure 624, which may have a peak-to-peak distance (pitch) from 50 to 1000 microns and a peak height from 50 to 2000 microns. The anti-migration microstructure pattern 606 as disclosed herein may also include a second set of microstructures 626, which may have a diameter from 10 to 100 microns, a pitch from 20 to 200 microns, and a height from 1 0 to 100 microns. In addition, embodiments of the anti-migration microstructure pattern 606 disclosed herein may include a third set of microstructures 628, which may have a diameter from 1 to 10 microns, a pitch from 2 to 20 microns, and a height from 1 to 1 0 microns. In some embodiments, the anti-fouling microstructure pattern 610 may include nanoparticles 630 randomly dispersed around the surface of the device. In some embodiments, the nanoparticles 630 may be dispersed around the inner surface 61 of the support. In some embodiments, the circularly arranged pillars disposed about the inner surface 634 may have a diameter of from 1 to 10 microns, a pitch of from 2 to 20 microns, and a height of from 1 to 10 microns, which act as nucleation islands that induce deposition that preferentially exfoliates in response to fluid flow in the stent lumen 636. The fluid conducting microstructures 614 may include through-holes that conduct fluid from the stent outer surface 638 to the stent lumen 636.

[0108] In some embodiments, the anti-migration microstructure pattern 606 may also include a peak-to-peak distance of the first microstructures 624 selected to match the intrinsic wrinkle pitch to accommodate the shear force-induced target surface wrinkles in the spaces between the peaks of the microstructures 624 .

[0109] The size of antifouling nanoparticles 630 can range from 1 to 100 nanometers and can present a hydrophobic surface. The size of microfeatures 628 can be selected to be more oleophilic relative to nanoparticle surface 630 so that deposition can be caused to accumulate in circularly arranged islands of microfeatures 628.

[0110] Reference now Figure 7 7A, 7B, and 7C show three embodiments of anti-fouling microfeatures 700. In one or more of these embodiments, the microstructured surface can produce a fluid dynamic effect that can push away particles entrained in the fluid flow. Figure 7 In the top illustration of , the microstructure 702 may include a top portion having an airfoil design with an upwardly turned wing tip 704 located at one or more distal ends of the top surface. The wing tip 704 may be configured to reduce turbulence of the fluid along the microstructure. Figure 7In the lower left portion of , microstructure 706 may include a configuration that mimics shark skin, which may include a top portion 708 having a serrated edge attached to a flared base post 710. In some embodiments, top portion 708 may be planar or curved. In some embodiments, top portion 708 may include a center portion having a volume that is thicker than the volume of the edges. Figure 7 In the lower right portion of FIG. 7 , microstructure 712 is a combination of the previous embodiments, where the top portion 708 may include a set of microstructures including a serrated edge and fins 714 protruding outwardly from the surface of the top portion.

[0111] In one or more embodiments, one or more textures can extend completely through the thickness of the coating. In one or more embodiments, one or more textures are blind textures (e.g., cavities, depressions, textures with bottoms, textures that do not extend from the second surface to the first surface).

[0112] In some embodiments, Figure 3-6 As shown in , the micropillars can be of any geometric shape, including but not limited to cylinders, prisms with rectangular or polygonal bases, pyramids, ridges, squares, ellipses, etc. In some embodiments, the micropillars can be a combination of the above-mentioned layered arrangements. The layered arrangement results in an overall texture that can be a complex and non-traditional shape, with multiple protrusions, valleys and / or ridges on multiple surfaces, which are not limited to cross-sections of circles, squares, polygons, etc. Individually, the texture can be a micropillar with, for example, 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 cross-section, an octagonal cross-section, a nonagonal cross-section, a decagonal cross-section, other polygonal cross-sections, or non-traditional shaped cross-sections. In some embodiments, the cross-section of any particular type of texture structure has a smaller effect on the surface properties than the surface energy domains produced by juxtaposing and stacking different texture structures.

[0113] It will be understood by those skilled in the art that when designing a surface to produce a desired effect, structural dimensions (height, width, diameter, pitch, slope, and length) may be considered. One or more of the microstructure textures described elsewhere herein may have a cross-section of a first dimension "h" and a second dimension "d", where the first dimension "h" may be the maximum distance between the outer surface of the base and the end of the structure, and the second dimension "d" is the maximum distance between two opposing sides (e.g., of a column). In some embodiments, "h" may relate to the "height" of the structure, while "d" may relate to the "diameter" of the structure. In some embodiments, "h" may be the total height, or "h" may refer to a specific length of a structural component. The same is true for "d", where the diameter may be the total diameter of the structure, or may be a specific diameter of a structural component. For example, for embodiments with a circular cross-section, the second dimension may be the diameter. For a square cross-section, the diameter may be measured from two opposing sides. For a rectangle, the major dimension may be between two shorter opposing sides. For a star-shaped cross-section, the major dimension may be measured between two opposing points. And for a hexagonal cross-section, the major dimension may be between two opposing points. In some embodiments, the second dimension "d" may be between the midpoints of two opposing sides. In at least one embodiment, a cross section of the microcolumn taken in a radial direction has at least four sides.

[0114] Embodiments of the present disclosure contemplate polygonal cross-sections that may include all sides of equal length, or may include a combination of sides of equal length and unequal length, or may include all sides of unequal length. Embodiments of the present disclosure contemplate multiple columns having a variety of cross-sectional shapes, including traditional shapes (e.g., circular, square, rectangular, hexagonal, polygonal, etc.) and non-traditional shapes with a perimeter, wherein at least a portion of the perimeter is curved. In at least one embodiment, the microcolumn may be a solid structure. In other embodiments, the microcolumn may be a partially solid structure. Still in other embodiments, the microcolumn may be a hollow structure. In at least one embodiment, each microcolumn may have a constant cross-section, but in other embodiments, the microcolumn may have a variable cross-section. In at least one embodiment, the microcolumn structure may extend vertically from the base. In at least one embodiment, the microcolumn structure may extend from the base at a non-perpendicular angle, wherein the geometric center of the microcolumn end may be laterally offset from the geometric center of the base area covered by the microcolumn. For example, the longitudinal axis of the microcolumn extending through the geometric center of the lateral cross-section may form an angle of less than 90 degrees with the base. In at least one embodiment, a plurality of micropillars may be arranged in a hierarchical arrangement in one or more specific micropatterns.

[0115] In one or more embodiments, the texture may take any shape and size described elsewhere herein. Typically, the layered arrangement may include a base structure. In some embodiments, the base structure may be flat, may vary continuously like a sine curve, may be stepped (e.g., as steps that rise and fall), may be perforated, or otherwise vary in a random or regular pattern. For example, in a two-dimensional sine curve, the pattern may be characterized by a wavelength or a range of wavelengths. One aspect of the present invention is understood to include a second set of textures that may be disposed on top of the base structure. The second texture may be arranged as a column, ridge, pyramid, etc., as previously listed. The second set of textures may also include feature size measurements, which may include pitch, height, diameter, width, slope, etc. In some embodiments, the size measurement of the base may be greater than the size measurement of the second set of textures. In some embodiments, the ratio between the first and second measurements is between 1:0 and 0.5. In some embodiments, there may be a third set of textures disposed on the second set of textures, and optionally disposed on the first set of textures between the structures of the second set of textures. Depending on the desired effect, the ratio between these size measurements may be adjusted to produce the desired effect. However, it will be appreciated that simply "tuning" the dimensional measurements to produce the desired effect is not a trivial task and thorough experimentation must be performed to establish the dimensional measurements to produce the desired effect. Various features cannot simply be selected and simply produce the desired results. Small changes in one dimensional measurement or in different geometries may have undesirable effects on the properties of the microstructured surface.

[0116] For the embodiment that microstructure can produce anti-fouling effect, the pitch of adjacent microstructure (such as column) can be relatively small relative to its height. For example, the height of microstructure can be 1 to 10 times of the pitch between microstructures. Higher height and pitch ratio tend to make the surface more hydrophobic and have low surface energy. Low surface energy structure can tend to resist the deposition of ion parts that can be usually found in biological tissue. If the desired effect of microstructure surface is to promote cell migration along the surface, the structure size can be selected to produce the surface energy gradient along the surface. Such structure size and position can be designed so that cells can easily bridge and travel along the structure, and thus migrate across the surface. On the contrary, microstructure surface with deep valleys around the surface may tend to prevent cell migration. It will be appreciated that cells depend on the continuity of attachment sites in order to breed along the surface. Therefore, the combination of high columns closely spaced together (that is, small spacing) makes it difficult for cells to fit between adjacent columns, which can have the desired effect of promoting cell cross-surface breeding without cell growth into the surface. It will be appreciated that due to the complications and problems arising in this case, cells may be particularly prevented from growing inwardly into the support surface. In contrast, a microstructured surface with structures of appropriate size and location can result in cells being directed to the tissue defect for cell repair without cell ingrowth that may cause difficulty in scaffold removal. In some embodiments, the scaffold may be textured to resist migration relative to the deployment site. Anti-migration surface textures may typically include Wenzel-Cassie wetting states. Such surface textures may tend to produce hydrophilic attraction and hydrophilic repulsion zones that are in close proximity to each other, thereby generating forces that resist scaffold migration.

[0117] In certain embodiments disclosed herein, the device of the present invention can be a wire braided stent. In some embodiments, the spacing of the wires relative to each other can match the eigenmodes of the tissue to which the stent will be deployed. The eigenmodes can be bending eigenmodes or can be peristaltic eigenmodes or both. When one or more eigenmodes are excited by the deployment of the stent, the anti-migration coating can naturally deform to engage the target eigenmodes. In some embodiments, the stent structure can be configured so that it induces a target microstructure in the polymer coating, which can then make the coating thinner and enable the stent to be more easily deployed when expanded.

[0118] In some embodiments, the close contact between the surface texture and the target lumen surface is ideal. In some embodiments, the gap between the surface texture and the target surface is ideal. In certain embodiments, the gap may be less than about 2 times of the maximum surface texture height on average. If 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 the frictional engagement or any interlocking mechanism between the micro-features (e.g., micro-pillars, textures, etc.) of the device and the target tissue. On the contrary, there is a fluid dynamic engagement between the surface, which produces an anti-migration effect. On the contrary, if frictional engagement with tissue is required, this function can be added to the surface pattern of the present specification by designing at least a portion of the surface features to provide this engagement. Therefore, in at least one embodiment, one or more specific microstructures are selected, which have micro-pattern geometry and size suitable for specific applications (e.g., anti-scaling, promoting biological tissue formation, desired anti-migration properties, anti-migration properties, etc.).

[0119] In one embodiment, the micropillars in a micropattern may all 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 in discrete portions of the polymer coating. Thus, in at least one embodiment, the micropattern may include portions where the micropillars have a first configuration and portions where the micropillars have a second configuration. Furthermore, embodiments may include a polymer coating having only one micropattern or a polymer coating having multiple micropatterns. Thus, when a single stent is used, the polymer coating may be tailored to the specific structural features and desired characteristics of a body lumen.

[0120] Similarly, in one or more embodiments, the texture can be constructed and arranged in the same manner as described herein for the micropillars disposed on the two-dimensional sinusoidal variation base. That is, in at least one embodiment, the texture in the micropattern can have a discrete shape combined with a continuous shape, and in other embodiments, the texture can vary in shape along the polymer coating. Therefore, 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. In addition, embodiments include polymer coatings having only one micropattern (e.g., random texture, micropillar, etc.) or polymer coatings having multiple micropatterns (e.g., two or more different texture micropatterns, two or more micropillar micropatterns, one or more texture micropatterns and one or more micropillar micropatterns in combination). Therefore, the polymer coating can be customized according to the specific structure and / or anatomical features of the body lumen (e.g., blood vessels, etc.), and the desired frictional engagement or interlocking can be achieved when using a single stent. In one or more embodiments, the micropattern can include one or more textures combined with one or more micropillars (e.g., a micropattern including a first number of textures alternating with a second number of micropillars, etc.). In one or more embodiments, the polymer coating can include a micropattern of micropillars and a micropattern of textures, wherein the micropatterns may overlap or may not overlap.

[0121] In some embodiments, the end of the protrusion (e.g., micro-column) farthest from the outer surface of the base can be shaped to improve tissue adhesion. In one or more embodiments, the end can be tapered, pointed, rounded, concave, convex, serrated, and / or worn. The end of each second protrusion can also include a plurality of first columns that are smaller in scale than the second micro-columns.

[0122] Similarly, in some embodiments, the second surface of the tissue engaging portion can be adaptively changed (e.g., shaped, textured, modified, etc.) to improve tissue adhesion. In one or more embodiments, the textured side surface and / or bottom surface can be tapered, grooved, perforated, concave, convex, serrated, and / or worn.

[0123] In at least one embodiment, the protrusions may further include terminal features such as mushroom-shaped terminals with involute curvature, downwardly pointing ridges, and / or multiple protuberances with concave centers extending outward from the surface of the micropillar. In some embodiments, the terminal surface may include multiple depressions extending inward from the surface of the micropillar, multiple ridges concentrically arranged on the terminal surface of the micropillar, a tip at or near the end of the protrusion that is softer or more rigid than the rest of the protrusion, a worn tip, a convex tip, a flared tip, a concave tip, a tip having a first dimension greater than the diameter of the micropillar extending outward from the base and the tip, and / or other features that may be coated with a thin layer of material having a specific surface energy that can be used to differentiate the surface energies of adjacent surfaces such that a Wenzel-Cassie domain is established that can be used to grip, improve the stiffness and / or flexibility properties of the interface between the device and tissue, and any combination of features thereof.

[0124] In at least one embodiment, the tip can be made of a different material than the rest of the protrusion. Similarly, the end and / or side surfaces of the texture can be shaped to improve tissue adhesion, similar to that described above with respect to micropillars. For example, the texture can include features such as a smooth surface, a rough surface, a plurality of ridges extending outward from the surface of the texture to create capillary action aspects, a plurality of depressions extending inward from the surface of the texture, a plurality of ridges on the surface of the texture, a worn end, a convex top, a flared bottom, a concave top, a bottom having a first dimension greater than a characteristic diameter of the protrusion extending between a second surface and the end, and / or other features that may affect flow aspects, which may improve capillary action aspects for clamping, stiffen the interface between the device and tissue, or improve the flexibility characteristics of the device by providing microscale sliding or flow aspects, and / or any combination of features thereof.

[0125] In at least one embodiment, the micropattern may include microridges and / or textures that are equally spaced (pitch) at a first distance in the first region of the base in the micropattern and equally spaced at a second distance (which may be different from the first distance) in the second region of the base in the micropattern. In at least one embodiment, the microstructure is a curved array. In at least one embodiment, the micropattern of the first curved array of microstructures may intersect with the second curved array of microstructures at a certain angle to form a grid pattern (e.g., a square array). In at least one embodiment, the micropattern of the microstructure is a regular n-polygon array (e.g., a hexagonal array), wherein, at the center of the microstructure forming the polygon, the microcolumn or texture may or may not exist at the center of the polygon. In other words, in the micropattern, the microcolumns and / or textures are arranged in an array in the micropattern of the microstructure, wherein the rows and columns of the array may or may not be perpendicular.

[0126] In one or more embodiments, each micropillar or texture can have a longitudinal axis, and the micropillars can be axially aligned in at least one of an axial direction of the device (e.g., arranged in rows parallel to the longitudinal axis of the device) and a circumferential direction (e.g., arranged in rows extending circumferentially around the longitudinal axis 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.

[0127] In some embodiments, the micropattern may cover only a portion of the base instead of the entire base. The micropattern of micropillars or textures may be arranged spirally on the base. In one or more embodiments, the first micropattern may be arranged longitudinally along the base, while the second micropattern is arranged circumferentially around the base so that the micropattern forms a mosaic-like structure. The micropillars may be arranged in rows (e.g., parallel to the longitudinal axis of the stent), and may be arranged in multiple continuous or discontinuous rows (e.g., aligned row segments separated by gaps). Discontinuous rows (and circumferentially oriented columns) may extend across the mosaic, where the discontinuous length is five times the spacing distance.

[0128] With regard to materials for polymer coatings, it may be useful that the material has a variety of properties that are useful for the environment in which the material is produced and deployed. For example, the material can be sufficiently flexible and / or elastic to produce ductile contact with tissue, be able to withstand processing for producing polymer coatings, and / or adapt to stent mechanics (e.g., elongation and conformability to tortuous anatomical structures). Examples of materials to be considered include, but are not limited to, flexible silicones, polyurethanes, hydrogels, mucoadhesive substrates, pressure-sensitive adhesives, and other suitable elastomers (e.g., synthetic rubbers). In some embodiments, a more rigid substrate can be used in a discrete configuration. Examples of acceptable rigid materials include, but are not limited to, polypropylene, polylactic acid polymers, PEEK, and polyacrylics.

[0129] In one or more embodiments, the coating having a micropattern may include and / or be formed from a biologically derived protein structure (e.g., collagen, etc.). Other acceptable materials may include any flexible, biocompatible, and non-biodegradable polymer. For palliative care stent applications, it may be useful for the coating to include one or more non-biodegradable polymers and / or materials with a degradation profile (which may be useful for specific stent applications and implantation sites). In one or more embodiments, the coating may be biodegradable, such as to allow stent removal (e.g., after some portion or all of the coating has degraded). Applications where stent removal may be useful include support during perforation healing, dilation of benign structures, and surgical bridging.

[0130] In at least one embodiment, the polymer coating with micro-pillars and / or ridges can include polymerized hyaluronic acid, which can biochemically conform to the lumen wall. Hyaluronic acid can also swell in a liquid environment. The microstructured device composed of hyaluronic acid can grasp the target tissue with a pincer-like motion due to the swelling of the microstructure.

[0131] In at least one embodiment, the polymer coating may include at least one therapeutic agent. In other embodiments, another coating including a therapeutic agent may be applied to the polymer coating. Whether it is a part of the polymer coating or another coating, the therapeutic agent may be a drug or other pharmaceutical product, such as a non-genetic agent, a genetic agent, a cell material, an extracellular matrix removed by protein, etc. 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, etc. When the reagent includes a genetic therapeutic agent, this genetic agent may include, but is not limited to, DNA, RNA, mRNA, siRNA, and their respective derivatives and / or components, particularly when this genetic derivative is combined with a polymer surface. The therapeutic agent may also include a cell material, wherein the cell material may include, but is not limited to, cells of human and / or non-human origin and their respective components and / or derivatives thereof. In one or more embodiments, suitable therapeutic agents may include small organic molecules, peptides, oligopeptides, proteins (e.g., "hedgehog" proteins, etc.), nucleic acids, oligonucleotides, genetic therapeutic agents, non-genetic therapeutic agents, vectors for delivering genetic therapeutic agents, cells and / or therapeutic agents identified as candidates for vascular treatment regimens, etc., and combinations thereof.

[0132] In one or more embodiments, one or more therapeutic agents may be included in or on the polymer coating, including micropillars and / or ridges. In some embodiments, plant derivatives such as terpenes (particularly triterpenes), various acids (particularly boswellic acid), and various phenols and antioxidant plant derivatives may be used as therapeutic agents.

[0133] In one or more embodiments, the base can be formed of the same material as the structure and / or microcolumns of the tissue engaging portion. In one or more embodiments, the microcolumns and / or structures are formed of one material and the base is formed of a different material. In one or more embodiments, the microcolumns and / or structures are formed of layers of material, and these layers can be the same material or can be different materials, depending on the characteristics required for the desired interaction of the device with the target tissue. Since differences in surface energy between adjacent layered sites may play a role in establishing the Wenzel-Cassie interface of the present invention, the difference in surface energy can be enhanced by coating some of the microstructure tips or domain walls with a thin layer of material having the desired ionic content. Chemical coatings can be used instead of surface textures because surface texture and surface chemistry can be understood to be interchangeable from a surface energy perspective.

[0134] Compared to similar devices / stents that rely on frictional engagement with tissue, the devices of the present disclosure can be understood as having a less abrasive positioning interaction with the lumen wall of the target tissue when inserted into the lumen. Therefore, the devices disclosed herein can be more easily removed using traditional removal techniques. In at least one embodiment, the device can be provided with a suture or removal ring on one end. In at least one embodiment, the removal ring can be provided on the distal end of the device. It should be noted that the term "distal" mentioned herein refers to the direction away from the operator of the device of the present disclosure, while the term "proximal" mentioned herein refers to the direction toward the operator of the device of the present disclosure. Although sutures or removal rings are known in the art for removing endoprostheses, the sutures or removal rings have been provided on the proximal end of the stent, in other words, on the end closest to the physician. Here, the sutures or removal rings are applied to the opposite ends of the endoprosthesis. In at least one embodiment, the physician can grasp the ring by placing the physician's tool within and through the lumen of the endoprosthesis, grasping the ring at the distal end, and then by applying an axial force to the ring, the distal end of the endoprosthesis can be folded inward and pulled through the lumen of the endoprosthesis itself (i.e., the device is inverted). Thus, using this removal method, the micro-pillars can be peeled off the vessel wall when the stent is turned inside out to remove the endoprosthesis. This removal technique may be desirable because the surface texture of the present disclosure can have reduced adhesion in peel forces (perpendicular displacement) compared to surface adhesion in shear forces (parallel displacement). In other embodiments, the physician can grasp the ring from the outside of the endoprosthesis or at the end of the endoprosthesis.

[0135] In order to manufacture the endoprosthesis, several methods can be used. The polymer coating can be formed (e.g., molded) separately from the stent (e.g., as a polymer film, a hydrogel film, a thin fiber network, etc.), and then adhered to the stent (e.g., the outer surface of the stent), wherein an optional adhesive layer is disposed between the outer surface of the stent and the substrate (e.g., the first surface) of the polymer coating (e.g., applied to at least a portion of one or both of the first surface of the substrate and the outer surface of the stent). The polymer material can be injected into a reversed mold with a micropattern to produce a polymer coating with a micropattern of microfeatures (e.g., micropillars, textures, etc.). In addition, a vacuum pump system can be used to extrude the polymer material through the mold. In at least one embodiment, the polymer coating can be produced using soft lithography.

[0136] In one or more embodiments, an etching technique can be used to produce a coating, wherein material is removed from a layer of coating material to produce a micro-pattern of a polymer coating. In another embodiment, a technique called hot embossing can be used, which involves punching a partially cured polymer into the desired shape of a polymer coating and then curing it before applying it to the stent. Stamping may include the use of a solvent or may not include the use of a solvent. In one or more embodiments, the stent can be coated by any suitable method (e.g., spraying, dipping, injection molding, etc.), and then the texture is introduced into the coating after the stent is coated. In some embodiments, a fiber network with a microscale texture (e.g., voids) can be formed by electrospinning one or more fibers on a 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 appropriately sized laser beams (e.g., depending on the same or different size of the desired pattern) to form one or more micro-pillars and / or one or more micro-ridges.

[0137] In one or more embodiments, one or more parts of the coating can be separated from the support (for example, as one or more pads, etc.) and deployed in the body lumen. Then, for example, a glucose adhesive can be applied to the applicable part of the support to attach to the pre-deployed coating (for example, a bio-interaction pad). The radial expansion force of the support during and after deployment can activate the adhesive and adhere the support to the coating previously deployed in the body lumen. The glucose adhesive can be alginate. The alginate on the smooth surface can be dissolved in the tissue volume, so its adhesion effect will be temporary. However, this adhesive arranged on the valley part of the layered texture can be used for two purposes: 1) immediate adhesion, and 2) mucoadhesive is used as a medium that can enhance the domain wall between the hydrophilic region and the hydrophobic region. The glucose adhesive can enhance the natural Wenzel-Cassie boundary, giving the domain wall structure aspect rather than a simple equipotential surface. The glucose adhesive can actually solidify the Wenzel-Cassie domains initially established.

[0138] In one or more embodiments, a polymer coating having a negative texture (e.g., micropores) can be formed by using a technique known as particle dissolution (e.g., salt dissolution), wherein a composite material is formed from one or more polymer materials and one or more particles (e.g., soluble salts), and then the one or more particles (e.g., salts) from the composite material are dissolved (e.g., with a solvent) to obtain a composite material and / or polymer material having a texture or voids, wherein the one or more particles (e.g., salts) are removed. The salt can be an alginate, which provides capillary effect properties, using ion concentration to draw liquid into the voids formed by dissolution.

[0139] In one or more embodiments, a polymer coating with multiple textures can be formed by a technique called electrospinning (e.g., using an electric charge to pull very fine fibers from a liquid), wherein the polymer coating includes a plurality of fibers arranged at or near a substrate that forms a texture (e.g., a texture network, a void network) between the fibers. The technique known as electrowriting is the same concept, except that the filaments are directed to the target surface in a controlled manner using standard XY printing techniques. Specifically, consistent with the desired Wenzek-Cassie structure, the directional electrospinning method can precisely lay single fibers of different materials on top of previously laid fibers. In at least one embodiment, the stent surface includes alternating fibers of hydrophilic and hydrophobic materials arranged alternately, in a stacked manner, describing a polygonal grid (e.g., a rectangular grid). This directional electrospinning grid surface can provide the dual functions of positioning the stent and promoting healthy tissue growth, wherein fiber degeneration is downregulated, while functional muscle tissue and new blood vessel formation are upregulated. It has been recognized that the density of this stacked polygonal grid can promote a variety of macroscopic tissues, including repair morphology, dynamic morphology (e.g., muscle tissue layer), and pressure wall morphology. The latter may be appreciated to be of particular importance in the repair of fluid-conducting lumens.

[0140] In one or more embodiments, the use of salt leaching and / or electrospinning can be used to provide a polymer coating having one or more textures that form a texture network (e.g., multiple textures connected along a substrate fluid). In some embodiments, when the polymer coating includes a texture network that penetrates the substrate, or when the substrate has openings that promote tissue growth, cell ingrowth can be enhanced. In one or more embodiments, any of a variety of therapeutic agents (e.g., growth factors) can be included on, included within, and / or combined with the texture network to promote tissue ingrowth when the micropatterned polymer coating contacts the tissue, including but not limited to fibronectin and those described elsewhere herein.

[0141] In at least one embodiment, the coating can be molded into a substantially tubular structure, wherein the lumen is defined by the substrate of the coating. A temporary adhesive layer or alternatively a soft hydrogel layer can be applied to the stent or to at least a portion of the outer surface of the substrate of the coating. In at least one embodiment, the adhesive layer can substantially cover the entire outer surface of the substrate 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 can be applied to ensure that the coating is properly adhered to the stent via the adhesive layer. The adhesive layer can include a silicone coating, other suitable adhesives or an initiating solution that enables the coating to adhere to a metal or polymer stent (or the stent coating thereon).

[0142] In one or more embodiments, instead of being molded into a tubular structure, the coating can be molded into a strip attached to the outer surface of the stent. For example, the strip can be arranged in a spiral manner around the stent, or arranged on a circumferential ring, or in a spiral configuration that rotates in the opposite direction. In some embodiments, the strip can be applied as a peripheral strip that is circumferentially attached around at least a portion of the circumferential periphery of the stent. In some embodiments, the strip can be a longitudinal strip attached to the stent longitudinally. In some embodiments, the stent can be spirally wrapped around the stent. In some embodiments, the coating can be applied as a single strip or as multiple strips. When the coating is applied as multiple strips, directly adjacent strips can be adjacent to each other or can be spaced apart from each other.

[0143] In at least one embodiment, the strip can be a partially 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 can be exposed. An adhesive layer can be applied to at least a portion of the substrate of the stent or coating. In at least one embodiment, heat and / or pressure can be applied to ensure that the coating is properly adhered to the stent via the adhesive layer. In at least one embodiment, a discrete micropattern of micropillars can be formed on a stent or polymer coating, and / or directly attached to the stent or polymer coating.

[0144] In one or more embodiments, the polymer coating can be formed by dipping the stent in the coating material without the need for an additional adhesive layer to connect the coating to the stent. For example, the stent can be inserted into a mold that includes a cavity and a tubular member. The cavity can be defined by the inner wall of the mold, which is the reverse of the desired micropattern. The stent can rest on the tubular member so that the inner surface of the stent can be arranged around the tubular member. The mold with the stent can be immersed in the coating material so that the coating material fills the mold and is attached to the stent. In some embodiments, temperature changes and / or pressure changes can be applied to the mold to cure the coating material. Once the coating material is cured to form a polymer coating, the endoprosthesis can be removed from the mold. Alternatively, a similar mold can be used to injection mold the polymer coating onto the stent. The coating material can be injected into the mold instead of dipping the mold into the coating material.

[0145] In one embodiment, the scaffold may include SMP. Examples of SMP include, but are not limited to, polynorbornene and copolymers of polynorbornene, blends of polybornene with KRATON.RTM. (thermoplastic elastomer) and polyethylene, styrene 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, polyolefins, nylons, 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.

[0146] In another alternative manufacturing method, the device can be formed by molding the outer surface modification onto a separate material layer, such as a non-woven material. As used herein, the term "non-woven" and variations thereof can refer to materials formed by casting, molding, spinning or extrusion techniques, but do not include typical textile forming techniques, such as braiding, weaving, knitting, etc. Non-limiting examples of useful polymeric materials for non-woven polymer graft portions include, but are not limited to, polyester, polypropylene, polyethylene, polyurethane, polynaphthalene, polytetrafluoroethylene, expanded polytetrafluoroethylene, silicone, and combinations and copolymers thereof.

[0147] In some embodiments, the devices disclosed herein can be treated with one or more therapeutic agents. "Therapeutic agent," "pharmaceutical," "pharmaceutically active agent," "drug," and other related terms are used interchangeably herein and include genetic therapeutic agents, non-genetic therapeutic agents, and cells. Therapeutic agents can be used alone or in combination. A variety of therapeutic agents can be used in conjunction with the present invention, including those used to treat a variety of diseases and conditions (i.e., prevent a disease or condition, reduce or eliminate symptoms associated with a disease or condition, or substantially or completely eliminate a disease or condition).

[0148] Non-limiting examples of useful therapeutic agents include, but are not limited to, adrenergic agents, adrenocortical steroids, adrenocortical suppressants, alcohol blockers, aldosterone antagonists, amino acids and proteins, ammonia detoxifiers, anabolic agents, antipyretic agents, analgesic agents, androgenic agents, anesthetics, anorectic compounds, anorectics, antagonists, anterior pituitary activators and inhibitors, anthelmintics, antiadrenergic agents, antiallergic agents, antiamoebic agents, antiandrogens, antianemic agents, antianginal agents, antianxiety agents, antiarthritic agents, antiasthmatic agents, Asthma, antiatherosclerotic, antimicrobial, anticholinergic, anticholinergic, anticoagulant, anticoccidial, anticonvulsant, antidepressant, antidiabetic, antidiuretic, detoxifier, antimanic, antiemetic, antiepileptic, antiestrogenic, antifibrinolytic, antifungal, antiglaucoma, antihemophilic, antihemophilic factor, antihemorrhagic, antihistamine, antihyperlipidemic, antihyperlipidemic, antihypertensive, antihypertensive, antiinfective, anti-inflammatory, non-keratinizing, antibacterial, antimigraine, antipruritic, anti Mycotic agents, anti-tumor agents, anti-cancer supplements, anti-neutropenia agents, anti-compulsive seizure agents, anti-parasitic agents, anti-Parkinson's drugs, anti-pneumocystis agents, anti-proliferative agents, anti-protozoal agents, antipruritic agents, anti-psoriatic agents, antipsychotic agents, anti-rheumatic agents, anti-schistosomiasis agents, anti-lipid leakage agents, antispasmodics, antithrombotic agents, antitussive agents, anti-ulcer agents, anti-urolithiasis agents, antiviral drugs, prostate hyperplasia therapeutic agents, blood sugar regulators, bone resorption inhibitors, bronchodilators, carbonic anhydrase inhibitors, cardiac depressants agents, radioprotectants, cardiotonic agents, cardiovascular agents, choleretics, cholinergic agents, cholinergic agonists, cholinesterase inactivators, coccidiostats, cognitive adjuvants and cognitive enhancers, inhibitors, diagnostic aids, diuretics, dopaminergic agents, ectoparasiticides, emetics, enzyme inhibitors, estrogens, fibrinolytic agents, free oxygen radical scavengers, gastrointestinal motility agents, glucocorticoids, gonadal stimulating factors, hemostatic agents, histamine H2 receptor antagonists, hormones, cholesterol-lowering agents, hypoglycemic agents, hypolipidemic agents, hypotensive agents, HMGCoA reductase inhibitors, immunizing agents, immunomodulators, immunoregulators, immunostimulants, immunosuppressants, impotence treatment agents, keratolytics, LHRH agonists, luteolytics, mucolytics, mucoprotectants, mydriatics, nasal decongestants, neuroleptics, neuromuscular blockers, neuroprotectants, NMDA antagonists, non-hormonal sterol derivatives, oxytocics, plasminogen activators, platelet activating factor antagonists, platelet aggregation inhibitors, post-stroke and post-head trauma treatment, progestins, prostaglandins, prostate growth inhibitors Preparations, thyroid stimulating hormone pro-agents, psychotropic drugs, radiopharmaceuticals, redistribution agents, scabicides, sclerosants, sedatives, sedative-hypnotic agents, selective adenosine A1 antagonists, adenosine A2 receptor antagonists, 5-hydroxytryptamine antagonists, 5-hydroxytryptamine inhibitors, 5-hydroxytryptamine receptor antagonists, steroids, stimulants, thyroid hormones, thyroid suppressants, thyroid mimetics, sedatives, unstable angina agents, uricosuric agents, vasoconstrictors, vasodilators, wound healing agents, wound healing agents, xanthine oxidase inhibitors, etc. and combinations thereof.

[0149] Useful non-genetic therapeutic agents for use in conjunction with the present invention include, but are not limited to (a) antithrombotic agents such as heparin, heparin derivatives, urokinase, clopidogrel, and dextrorotatory phenylalanine proline arginine chloromethyl ketone; (b) anti-inflammatory agents such as dexamethasone, prednisolone, corticosterone, budesonide, estrogen, sulfasalazine, and mesalazine; (c) anti-tumor / anti-proliferative / anti-miotic agents such as paclitaxel, 5-fluorouracil, cisplatin, vinblastine, vincristine, epothilones, endostatin, and tadalafil; (d) anti-inflammatory agents such as tadalafil, 5-fluorouracil, cisplatin, vinblastine, vincristine, epothilones, endostatin, and tadalafil. (d) anesthetics, such as lidocaine, bupivacaine and ropivacaine; (e) anticoagulants, such as D-Phe-Pro-Arg chloromethyl ketone, compounds containing RGD peptides, heparin, hirudin, antithrombin compounds, platelet receptor antagonists, antithrombin antibodies, antiplatelet receptor antibodies, aspirin, prostaglandin inhibitors, platelet inhibitors and tick antiplatelet peptides; (f) vascular cell growth promoters, such as growth factors, transcription activators and translation promoters; (g) vascular cell growth inhibitors, such as growth factor inhibitors, growth factor receptor antagonists, transcription repressors, translation repressors, replication inhibitors, inhibitory antibodies, antibodies against growth factors, bifunctional molecules composed of growth factors and cytotoxins, and bifunctional molecules composed of antibodies and cytotoxins; (h) protein kinase and tyrosine kinase inhibitors (e.g., tyrosine phosphorylation inhibitors, genistein, quinoxaline); (i) prostacyclin analogs; (j) cholesterol-lowering agents; (k) angiogenin; (l) antimicrobial agents, such as triclosan, cephalosporins, aminoglycosides and nitrofurantoin; (m) cytotoxic agents, cell growth inhibitors and cell proliferation-affecting factors; (n) vasodilators; (o) agents that interfere with endogenous vasoactive mechanisms; (p) leukocyte recruitment inhibitors, such as monoclonal antibodies; (q) cytokines; (r) hormones; (s) HSP (i) inhibitors of β-adrenergic receptor antagonists (e.g., doxazosin, tamsulosin, terazosin, prazosin, and alfuzosin), calcium channel blockers (e.g., verapamil, diltiazem, nifedipine, nicardipine, nimodipine, and bepridil), β-adrenergic receptor agonists (e.g., β-adrenergic receptor agonists), and inhibitors of β-adrenergic receptor agonists. (e.g., dobutamine and salmeterol), beta-receptor antagonists (e.g., atenolol, metoprolol, and butoxamine), angiotensin-II receptor antagonists (e.g., losartan, valsartan, irbesartan, candesartan, eprosartan, and telmisartan), and anticonvulsant / anticholinergic drugs (e.g., oxybutynin hydrochloride, flavoxate, tolterodine, scopolamine sulfate, dicyclomine); (u) bARKct inhibitors; (v) phospholamban inhibitors; (w) Serca gene / protein;(x) immune response modifiers, including aminoquinolines, for example, imidazoquinolines, such as resiquimod and imiquimod; (y) human apolipoproteins (e.g., AI, AII, AIII, AIV, AV, etc.); (z) selective estrogen receptor modulators (SERMs), such as raloxifene, lasofoxifene, arzoxifene, miproxifen, ospemifene, PKS 3741, MF 101, and SR 16234; (aa) PPAR agonists, including PPAR-α, γ, and δ agonists, such as rosiglitazone, pioglitazone, nyglitazone, fenofibrate, bexarotene, meglitazone, troglitazone, and tesaglitazar; (bb) prostaglandin E agonists, including 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 β4; (ff) phospholipids, including phosphocholine, phosphatidylinositol and phosphatidylcholine; and (gg) VLA-4 antagonists and VCAM-1 antagonists. Non-genetic therapeutic agents can be used alone or in combination, including in combination with any of the agents described herein. ;

[0150] Other examples of non-genetic therapeutic agents (not necessarily exclusive of those listed above) include: taxanes, such as paclitaxel (including particulate forms thereof, e.g., protein-bound paclitaxel particles, such as albumin-bound paclitaxel nanoparticles, such as ABRAXANE), sirolimus, everolimus, tacrolimus, zotarolimus, Epo D, dexamethasone, estradiol, halofuginone, cilostazol, geldanamycin, chloralazine (ALT-711), ABT-578 (Abbott Laboratories), trapidil, leprostaglandin, actinomycin D, Resten-NG, AP-17, abciximab, clopidogrel, lidogrel, beta-blockers, BARKct inhibitors, phospholamban inhibitors, Serca 2 gene / protein, imiquimod, human apolipoprotein, growth factors (e.g., VEGF-2), and derivatives of the foregoing, as well as other substances.

[0151] Biodegradable polymers that can be used to form a device as disclosed herein, form at least a portion of a device as disclosed herein, or can be applied to a device or a portion of a device as disclosed herein can include a variety of materials. Examples of these 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 copolymers and derivatives thereof. Certain hydrogels (which are cross-linked polymers) can also be made biodegradable. These include, but are not limited to, polyesters, pluronic polysaccharides, poly(amino acids), copoly(ether-esters), polyalkylene oxalates, polyamides, poly(imidocarbonates), polyorthoesters, polyoxaesters, polyamide esters, polyoxaesters containing amide groups, polyanhydrides, polyphosphazenes, poly-α-hydroxy acids, trimethylene carbonate, poly-β-hydroxy acids, polyorganophosphazenes, polyanhydrides, polyesteramides, polyethylene oxides, polyester-ethers, polyethylene glycols, polyethylene glycol ethers, cyanoacrylates, poly(trimethylene carbonate), poly(imido carbonate), polyalkylene oxalates, polyvinyl pyrrolidone, polyvinyl alcohol, poly-N-(2-hydroxypropyl)-methacrylamide, polyethylene glycol, aliphatic polyesters, poly(orthoesters), poly(ester-amides), polyanhydrides, modified polysaccharides, and modified proteins. Some specific examples of bioresorbable 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-co-trimethylene carbonate), poly(ε-caprolactone-co-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.

[0152] The above disclosure is illustrative and not exhaustive. This specification will suggest many variations and substitutions to those of ordinary skill in the art. All such substitutions and variations are intended to be included within the scope of the claims, wherein the term "comprising" means "including but not limited to". Those skilled in the art may recognize other equivalents of the specific embodiments described herein, which are also intended to be covered by the claims.

[0153] Furthermore, specific features presented in the dependent claims may be combined with each other in other ways within the scope of the present disclosure, so that the present disclosure should be considered to be specifically directed to further embodiments also with any other possible combination of features of the dependent claims.

[0154] Therefore, although specific embodiments of the novel and useful anti-fouling stent of the present invention have been described, such references are not intended to be construed as limitations on the scope of the invention except as set forth in the appended claims.

Claims

1. An endoprosthesis for placement in a body lumen, comprising: A tubular member having an outer surface including a first hierarchical microstructural pattern arranged to produce a Wenzel-Cassie state and an inner surface that is superhydrophobic or oleophobic and includes a second microstructural pattern different from the first hierarchical microstructural pattern.

2. The endoprosthesis according to claim 1, characterized in that The tubular member further includes a polymer wall such that the outer surface and the inner surface are positioned on opposite sides of the polymer wall, and wherein at least one through-hole fluidly connects the outer surface and the inner surface.

3. The endoprosthesis according to claim 1, characterized in that The first hierarchical microstructure pattern includes a plurality of first microfeatures having a base and a top portion, wherein each first microfeature of the plurality of first microfeatures includes a base having an incurved post.

4. The endoprosthesis according to claim 3, characterized in that The first hierarchical microstructure pattern includes a plurality of second microfeatures disposed around top portions of the plurality of first microfeatures.

5. The endoprosthesis according to claim 4, characterized in that The plurality of first microfeatures can have a pitch between adjacent microfeatures of from 25 to 100 microns and a height of from 10 to 100 microns.

6. The endoprosthesis according to claim 1, characterized in that The second hierarchical microstructure pattern includes a plurality of microridges, wherein each microridge of the plurality of microridges has a pitch between adjacent microridges of from 100 nm to 10 microns.

7. The endoprosthesis according to claim 6, characterized in that Each microridge of the plurality of microridges comprises a length greater than a width.

8. The endoprosthesis according to claim 7, characterized in that The plurality of microridges includes a subset of microridges wherein each adjacent microridge gradually increases in height.

9. The endoprosthesis according to claim 8, characterized in that The plurality of microridges includes a second subset of microridges wherein each adjacent microridge gradually decreases in height.

10. The endoprosthesis according to claim 9, characterized in that The first subset of micro-ridges is adjacent to the second subset of micro-ridges.

11. The endoprosthesis according to claim 7, characterized in that The length of each micro-ridge of the plurality of micro-ridges is arranged coaxially with the central axis of the tubular member.

12. The endoprosthesis according to claim 7, characterized in that The length of each micro-ridge of the plurality of micro-ridges is arranged circumferentially along the inner surface of the tubular member.

13. The endoprosthesis according to claim 1, characterized in that The first hierarchical microstructure covers a portion of the outer surface.

14. The endoprosthesis according to claim 1, characterized in that The outer surface includes a third microstructural pattern different from the first microstructural pattern, the third microstructural pattern configured to transport a fluid from a first location to a second location.

15. The endoprosthesis according to claim 14, characterized in that The third microstructure pattern includes a plurality of microfeatures having a pitch between adjacent microfeatures of from 5 to 50 microns, a width of from 1 to 20 microns, and a height of from 5 to 50 microns.

16. The endoprosthesis according to claim 1, characterized in that The tubular member includes a first end and a second end, the first end and the second end being flared relative to a central portion of the tubular member.

17. An endoprosthesis for placement in the gastrointestinal tract, comprising: A tubular member having an outer surface and an inner surface, the outer surface comprising a multi-fractal first hierarchical microstructure pattern, the outer surface further comprising a plurality of pores, and the inner surface being superhydrophobic or oleophobic and comprising a second microstructure pattern different from the first hierarchical microstructure pattern.

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