medical devices

Abstract

Improving the attachment of medical devices, including stents, to tissue. [Solution] A medical device comprising: (a) a stent component having both ends, a plurality of first structural elements extending circumferentially of the stent component, and a plurality of second structural elements extending linearly in approximately the longitudinal direction of the stent component, each of the plurality of second structural elements connecting adjacent first structural elements to define cells; (b) a coating material disposed on the stent component; and (c) a bonding material bonded to the first structural elements and second structural elements, the coating material, or both, wherein the bonding material does not span each of the cells defined between adjacent first structural elements, and the bonding material comprises a tissue solder material containing a protein, and the medical device is configured such that when the tissue solder material is heated by a heat-applying energy source, a heat-induced protein denaturation-regeneration process occurs in the tissue solder material, causing the stent component to adhere to body lumen tissue.

Description

[Technical Field]

[0001] The present invention relates to compositions, devices, kits, and procedures for attaching medical devices, including stents, to tissue. [Background technology]

[0002] A stent is a thin mesh tube used to treat narrowed or weak lumens (e.g., arteries, veins, bile ducts, esophagus, intestines, lungs, etc.), for example, to counteract constriction of the lumen due to various diseases and conditions. Stents can be formed from metals, polymers, or other suitable materials. Stents can be biostable or bioabsorbable, drug-eluting or non-drug-eluting. The most common use of stents is in coronary arteries. Besides coronary stents, other common types of stents include peripheral stents, ureteral stents (e.g., to ensure patency of the ureter), biliary stents (e.g., to treat obstructions in the bile or pancreatic duct), esophageal stents (e.g., to treat obstructions in the esophagus), intestinal stents (e.g., to treat obstructions in the small intestine or colon), and airway stents (e.g., to treat obstructions in the trachea or bronchi), among others.

[0003] In some cases, stents are coated. When the coating of a coated stent is porous, it is typically used in the vasculature and is often called a stent-graft. Stent-grafts are used to treat abdominal aortic aneurysms and weakened peripheral arteries. Other coated stents can be used to treat, among other uses, malignant or bilateral strictures of the esophagus, as well as leaks and / or perforations in various body lumens. In some cases, coated stents are temporarily placed and removable.

[0004] Fixation is crucial to the placement of stents, whether they are covered, partially covered, or uncovered, because migration of such implants can compromise the procedure and lead to further complications.

[0005] As a specific example, placement of coated, self-expanding metallic or polymeric stents has historically been the first choice for palliative treatment of unresectable esophageal cancer. These stents are also highly effective in managing benign (digestive, postoperative, corrosive) strictures, esophageal leaks, perforations, and fistulas. In most cases, rapid relief of dysphagia and adequate oral nutrition can be achieved. If the stent migrates from the esophagus into, for example, the stomach or small intestine and causes an obstruction, the patient may suffer severe pain and fever, which may require additional surgery to remove the stent. The same is true for other GI and airway stents.

[0006] As another specific example, abdominal aortic aneurysm (AAA) stent grafts are often used to address aneurysms, which are characterized by a weak arterial wall. Over time, blood pressure and other factors can cause this weak area to inflate like a balloon, which can eventually enlarge and rupture. AAA stent grafts are designed to strongly seal against the artery above and below the aneurysm. The graft is stronger than the weakened artery, allowing blood to pass through the artery without pushing against the bulge. If the stent graft migrates, the seal above the aneurysm can be compromised. This can allow blood to flow into the aneurysm sac, which can grow and rupture, necessitating reintervention. [Prior art documents] [Patent documents]

[0007] [Patent Document 1] International Publication No. 2014 / 042875 [Patent Document 2] International Publication No. 2009 / 036014 [Patent Document 3] Special Publication No. 2011-523569 [Patent Document 4] Special Publication No. 2002-523136 Summary of the Invention [Problem to be solved by the invention]

[0008] The present invention has been made in view of the above-mentioned problems. [Means for solving the problem]

[0009] According to some aspects of the present disclosure, a stent-including device is provided that includes a bonded bonding material, the stent-including device being configured to bond to a lumen upon exposure to an energy source while the stent-including device is in contact with the lumen.

[0010] In some aspects, the present disclosure features a medical device including (a) a stent component, (b) an optional covering material, and (c) a bonding material bonded to the stent component, the optional covering material, or both, the medical device being configured for implantation in a patient and for bonding to adjacent patient tissue when the bonding material is exposed to energy from an energy source.

[0011] In certain embodiments that can be used in combination with any of the above aspects, the bonding material comprises a tissue solder material, the bonding material comprises a tissue solder and a photosensitive dye, or the bonding material comprises a tissue solder and an energy absorbing agent.

[0012] In certain embodiments that can be used in combination with any of the above aspects and embodiments, the binding material comprises a tissue solder selected from chitosan, albumin, collagen, elastin, fibronectin, nanopeptides, derivatives thereof, and combinations of two or more thereof.

[0013] In certain embodiments that can be used in combination with any of the above aspects and embodiments, the bonding material comprises tissue solder and a photosensitive dye, wherein the photosensitive dye is selected from rose bengal dye, methylene blue dye, fluorescein dye, indocyanine green, basic fuchsin, phen, xanthan dye, riboflavin dye, lumichrome dye, flavin, lumiflavin dye, Reactive Black 5 dye, and combinations of two or more thereof.

[0014] In certain embodiments that can be used in combination with any of the above aspects and embodiments, the bonding material comprises a tissue solder and an energy absorbing agent, wherein the energy absorbing agent is selected from a chromophore, a superparamagnetic iron oxide nanoparticle (SPION), a gold nanorod, a gold nanoshell, a gold nanocage, and a combination of two or more thereof.

[0015] In certain embodiments that can be used in combination with any of the above aspects and embodiments, the bonding material comprises a tissue solder and a synthetic polymer, wherein the synthetic polymer is selected from polylactic acid, polyglycolic acid, poly(lactic-co-glycolic acid), polydioxanone, polycaprolactone, and combinations of two or more thereof.

[0016] In a further aspect, which can be used in combination with any of the above aspects and embodiments, the bonding material is bonded to the medical device by (a) coating at least a portion of the stent component, at least a portion of the optional covering material, or at least a portion of both with the bonding material; (b) incorporating the bonding material into at least a portion of the stent component, at least a portion of the optional covering material, or at least a portion of both; or (c) a combination thereof.

[0017] In a further aspect, which can be used in combination with any of the above aspects and embodiments, the bonding material is bonded to the ends of the medical device rather than to the center of the medical device, or the bonding material is provided as a series of bands or islands along the length of the medical device.

[0018] In a further aspect that can be used in combination with any of the above aspects and embodiments, the medical device includes an optional covering material. The covering material may, for example, cover the entire stent component or only a portion of the stent component. For example, in certain embodiments, only the ends of the stent component may be covered with the covering material, or the covering material may include a plurality of openings that provide areas of the stent component that are not covered by the covering material. In certain embodiments, the covering material covers only a portion of the stent component, and the bonding material is bonded to the stent component in areas of the stent component that are not covered by the covering material.

[0019] In a further aspect that can be used in combination with any of the above aspects and embodiments, the medical device includes an optional coating material that is sufficiently transparent to energy from an energy source such that a binding material disposed abluminally relative to the coating material can be activated using an energy source disposed luminally relative to the coating material.

[0020] Another aspect of the present disclosure provides a method of attaching a stent-containing medical device to a lumen, in which energy from an energy source is applied to a bonding material bonded to the stent-containing medical device, thereby activating the bonding material and attaching the stent-containing device to the lumen. In certain embodiments, a stent-containing medical device, such as a stent-containing medical device described in any of the above aspects and embodiments, is utilized in this method.

[0021] Yet another aspect of the present disclosure features a kit including any combination of two or more of the following items: (a) a medical device including a stent, the medical device including a stent component, an optional covering material, and an optional bonding material bonded to the stent component, the optional covering material, or both; (b) the bonding material in solid or liquid form; (c) a surgical device with or without an associated energy source configured to receive and deploy the medical device in a subject; (d) a guidewire with or without an associated energy source; or (e) a stand-alone energy source. In certain embodiments, a medical device including a stent, such as a medical device including a stent described in any of the above aspects and embodiments, is utilized in the kit.

[0022] An advantage of the present disclosure is that compositions, devices, kits, and procedures are provided that allow a medical device, including a stent, to be implanted within a body lumen and a bonding material to be activated, thereby minimizing or preventing migration of the device within the body lumen after implantation.

[0023] Another advantage of the present disclosure is that compositions, devices, kits, and procedures are provided whereby medical devices, including stents, particularly coated stents, can be implanted into a body lumen and the bonding material activated, thereby causing the device to adhere to the body lumen. [Brief explanation of the drawings]

[0024] [Figure 1] 1 is a schematic diagram of a stent including solder according to one embodiment of the present disclosure. [Figure 2] FIG. 10 is a schematic illustration of a stent including solder according to another embodiment of the present disclosure. [Figure 3] FIG. 10 is a schematic illustration of a stent including solder according to another embodiment of the present disclosure. [Figure 4] FIG. 10 is a schematic illustration of a stent including solder according to another embodiment of the present disclosure. [Figure 5A] FIG. 10 is a schematic illustration of a stent including solder according to another embodiment of the present disclosure. [Figure 5B]FIG. 10 is a schematic illustration of a stent including solder according to another embodiment of the present disclosure. [Figure 6] FIG. 10 is a schematic illustration of a stent including solder according to another embodiment of the present disclosure. [Figure 7A] 1 is a schematic diagram of a method of implanting a stent according to one embodiment of the present disclosure. [Figure 7B] 1 is a schematic diagram of a method of implanting a stent according to one embodiment of the present disclosure. [Figure 7C] 1 is a schematic diagram of a method of implanting a stent according to one embodiment of the present disclosure. [Figure 8A] 10 is a schematic diagram of a method of implanting a stent according to another embodiment of the present disclosure. [Figure 8B] 10 is a schematic diagram of a method of implanting a stent according to another embodiment of the present disclosure. [Figure 8C] 10 is a schematic diagram of a method of implanting a stent according to another embodiment of the present disclosure. [Figure 9] 10 is a schematic diagram of a method of implanting a stent according to yet another embodiment of the present disclosure. [Figure 10] 1 is a schematic diagram of an energy emitting device according to one embodiment of the present disclosure. [Figure 11] FIG. 10 is a schematic diagram of an energy emission device according to another embodiment of the present disclosure. [Figure 12] FIG. 10 is a schematic diagram of an energy emission device according to another embodiment of the present disclosure. DETAILED DESCRIPTION OF THE INVENTION

[0025] The present disclosure relates to methods, compositions, devices, and kits useful for implanting and securing medical devices, including stents, e.g., bare stents, drug-eluting stents, partially covered stents, and fully covered stents, in a body lumen of a subject, typically a vertebrate subject, more typically a mammalian subject, e.g., a human subject, a pet, or a livestock animal. The devices can be implanted and secured in various lumens, e.g., blood vessels (e.g., arteries, veins, etc.), lumens of the gastrointestinal tract (e.g., esophagus, stomach, duodenum, small intestine, large intestine, colon, bile duct, etc.), female urinary lumens (e.g., ureters, urethra, fallopian tubes, etc.), or airway lumens (e.g., trachea, bronchi, etc.), among others, to, for example, prevent migration within the lumen and / or form a seal with the lumen (e.g., in the case of covered stents). In various embodiments, devices including stents are used to provide one or more of the following functions, among others: maintaining patency of a body lumen; strengthening the wall of a body lumen; adhering to the wall of a body lumen; and preventing tissue in-growth into the body lumen.

[0026] According to one aspect, the present disclosure relates to a stent-containing device configured for implantation within a body lumen, the stent-containing device including (a) stent components, (b) an optional covering material, and (c) a bonding material. The bonding material is bonded to at least a portion of the stent-containing device (e.g., bonded to the stent components, the optional covering, or both) such that the stent-containing device can bond to adjacent patient tissue when exposed to energy. For example, the bonding material can be bonded to the device by one or more of the following strategies, among others: (a) the bonding material can be coated on all or a portion of the stent components; (b) the bonding material can be integral with all or a portion of the stent components; (c) the bonding material can be coated on all or a portion of the optional covering material; or (d) the bonding material can be integral with all or a portion of the optional covering material.

[0027] The device, including the stent, is introduced into a body lumen, such as a blood vessel, a lumen of the gastrointestinal tract, a female urinary tract lumen, or a lumen of the respiratory tract, among others, by a suitable procedure, and then energy is applied to the bonding material, thereby activating the bonding material and attaching the device, including the stent, to the tissue of the body lumen.

[0028] Depending on the tissue bonding mechanism utilized, various energy sources can be used to attach the device. The energy source can be, for example, a heat source or a light source, such as a laser or light-emitting diode (LED). Infrared and near-infrared laser sources include, among others, carbon dioxide (CO), thulium-holmium-chromium, holmium, thulium, and neodymium rare-earth doped garnet (THC:YAG, Ho:YAG, Tm:YAG, and Nd:YAG, respectively) lasers, and gallium aluminum arsenide diode (GaAlAs-based) lasers. Visible light sources include, among others, potassium titanyl phosphate (KTP) frequency-doubled Nd:YAG lasers and argon lasers. Other energy sources include radiofrequency sources (e.g., microwave sources), radiation sources (e.g., X-rays, gamma rays, etc.), or locally generated plasma. Argon plasma is currently used in a variety of medical applications, including argon beam coagulators, which ionize argon gas to create argon plasma, which is then used to deliver thermal energy to nearby tissue. In the present disclosure, an argon beam can be used as a heat source to bond tissue.

[0029] In certain embodiments, the energy source is provided in a stand-alone unit. In other embodiments, the energy source is combined with another device. For example, the energy source can be combined with a delivery device, such as a guidewire or catheter.

[0030] In some embodiments, the energy source is connected to a control unit, which controls the energy emitted from the energy source. Preferably, the amount of energy is sufficient to activate the bonding material without significantly damaging the underlying tissue. In some embodiments, the control unit is designed to accept user input (e.g., via physical buttons, a touchscreen, etc.), thus allowing a healthcare provider to set treatment parameters.

[0031] In some embodiments, the energy source is controlled without the use of a sensor (e.g., based on the surgeon's experience or based on an appropriate energy output algorithm). In other embodiments, a sensor is used in conjunction with the energy source to provide feedback on the amount of energy directed to the binding site, which feedback can be used to adjust the output of the energy source. For example, in certain embodiments, the sensor is a temperature sensor that detects the heat content of the binding site. In these embodiments, appropriate software can be utilized to adjust the output of the energy source based on input from the temperature sensor. The sensor can be provided, for example, in the same device as the energy source or in a different device than the device containing the energy source. The sensor can be provided, for example, in a medical device (with or without an energy source) used to deliver the device.

[0032] A variety of bonding materials can be used with the present disclosure. In this regard, the laser tissue soldering process is known in the surgical field, in which tissues are joined by applying a solder (typically a biological polymer) to the tissue and then using a laser to activate the solder and form a bond. Without wishing to be bound by theory, it has been reported that the mechanism of laser tissue soldering appears to involve a heat-induced protein denaturation-regeneration process. See, for example, B. Forer et al., Laryngoscope 116, June 2006, pp. 1002-1006.

[0033] Solder materials are used as bonding materials in the present disclosure to bond materials of devices, including stents, to tissue, for example, by applying heat to the solder material while the solder material is in contact with the materials of the devices, including stents (e.g., materials of stent components or optional coating materials) and tissue, such that the materials of the devices, including stents, are bonded to the tissue. As noted above, useful energy sources for applying heat include light sources (e.g., lasers), radio frequency sources (e.g., microwave sources), and plasma sources (e.g., argon beams), among others.

[0034] Particularly useful solder materials have a relatively low activation temperature and are bioabsorbable. For example, a solder can be bioabsorbed over time, typically between about 4 days and 6 months (e.g., 4 days to 1 week to 2 weeks to 1 month to 2 months to 3 months to 6 months) (i.e., a range between any two of these values), depending on the solder used. The bioabsorption rate can be adjusted within this range, or faster or slower than this range, by adjusting the solder chemistry.

[0035] Specific solder materials for use with the present disclosure include biologically-derived solders and synthetic solders. Examples of biologically-derived solders include biopolymers, such as polypeptides and proteins, including nanopeptides, such as albumin, collagen, elastin, fibrin, fibrinogen, thrombin, prothrombin protein derivatives, and polysaccharide-based solders, including chitosan, among others. Some embodiments utilize two, three, or more solder materials, such as those listed above. Specific examples include albumin and collagen, albumin and chitosan, collagen and chitosan, and albumin, collagen, and chitosan, among others, although many other combinations are possible.

[0036] Other polymers that can be added include, in particular, water-soluble or bioabsorbable polymers, such as synthetic water-soluble or bioabsorbable polymers, such as polylactic acid, polyglycolic acid, polydioxanone, polycaprolactone, tyrosine-based polyesters, tyrosine-based polycarbonates, polyesteramides, polyanhydrides, polyhydroxyalkanoates, polyethylene glycol, polyorthoesters, Pluronics, such as block copolymers of ethylene glycol and propylene glycol, polyamides, polyvinyl alcohol, hydroxy-substituted poly(meth)acrylates, polyethylene glycol-substituted (meth)acrylates, (methacrylic acid-b-polyethers), or copolymers derived from these monomers. One or more of these water-soluble or bioabsorbable polymers can be mixed with a biologically-derived solder, such as the solders described above, to modify the properties of the solder material. As a specific example, PLGA can be mixed with albumin to increase the flexibility of albumin solder.

[0037] In some embodiments, at least one energy absorber is used in the solder material to improve heating efficiency and / or heat distribution within the solder material. Energy absorbers include chromophores, such as photospecific dyes, e.g., indocyanine green (ICG), fluorescein, basic fuchsin, and phene, among other materials; nanometals, such as nanogold (e.g., gold nanorods, gold nanoshells, gold nanocages, etc.); and SPIONs (superparamagnetic iron oxide nanoparticles). Specific examples include, among many others, ICG-doped albumin, fluorescein-dye-doped albumin, and nanogold-doped albumin. Metal (e.g., gold) or semiconductor nanoparticles, including rods, nanoshells, and other shapes, can be included in the solder material and heated by excitation at their plasmon frequencies. For further information, see, for example, Alexander O. Govorov et al., "Generating heat with metal nanoparticles," Nano Today, Vol. 2, February 1, 2007, pp. 30-38.

[0038] Photochemical tissue bonding processes are known in the field of surgery. This process utilizes a photochemical reaction that occurs on closely coupled tissue surfaces (e.g., stained tissue surfaces placed in contact with each other) that have been stained with a photosensitive dye. Without wishing to be bound by theory, it is believed that the dye absorbs photons of visible light, promoting the formation of covalent bonds between molecules on the adjacent tissue surfaces. For example, reactive species generated upon photoactivation of the dye can react with potential electron donors and electron acceptors, such as amino acids in proteins (e.g., tryptophan, tyrosine, and cysteine). In this regard, a photochemical method for forming crosslinks in collagen type I molecules has been reported. Barbara P. Chan et al., Journal of Surgical Research, pp. 111-114, 2014. Research), 2002, Vol. 108, pp. 77-84.

[0039] In certain aspects of the present disclosure, a photosensitive dye is used to bond a device, including a stent, to the tissue surface by applying light of an appropriate wavelength to the photosensitive dye (e.g., mixed with a solder material or coated on the surface of a solder material placed in contact with and between the device, including a stent, and the tissue surface) and the solder material (e.g., a biosolder material, particularly including the solder materials described above), which is intimately bound to the device, including a stent, and the tissue surface, such that the device, including a stent, is bonded to the tissue. A light-emitting energy source, such as a low-power laser or a light-emitting diode (LED), among others, can be used for this purpose.

[0040] Specific examples of photosensitive dyes include xanthene dyes such as rose bengal, methylene blue, and fluorescein, riboflavin dyes (e.g., riboflavin-5-phosphate), lumichrome dyes, lumiflavin dyes, Reactive Black 5, thiazine dyes, naphthalimides (e.g., 1,8-naphthalimide), erythrosine, N-hydroxypyridine-2-(1H)-thione (N-HTP), protoporphyrin I through protoporphyrin IX, coproporphyrin, uroporphyrin, mesoporphyrin, hematoporphyrin, and sapphyrin, chlorophylls such as bacteriochlorophyll A, Photofrin®, synthetic diporphyrins, and dichlorins, Phthalocyanines with or without metal substituents, chloroaluminum phthalocyanines with or without various substitutions, O-substituted tetraphenylporphyrins, 3,1-mesotetrakis(O-propionamidophenyl)porphyrin, tin and zinc derivatives of verdin, purpurin, octaethylpurpurin, etiopurpurin, hydroporphyrins, bacteriochlorins of the tetra(hydroxyphenyl)porphyrin series (e.g., protoporphyrin I to protoporphyrin II), porphyrin IX, coproporphyrin, uroporphyrin, mesoporphyrin, hematoporphyrin, and sapphyrin), chlorins, chlorin e6, mono-1-aspartyl derivatives of chlorin e6, di-1-aspartyl derivatives of chlorin e6, tin(IV) chlorin e6, meta-tetrahydroxphenylchlorin, benzoporphyrin derivatives, benzoporphyrin monoacid derivatives, tetracyanoethylene adducts of benzoporphyrins, dimethylacetylenedicarboxylic acid adducts of benzoporphyrins, Diels-Adler adducts, monoacid ring "a" derivatives of benzoporphyrins, sulfonated aluminum PC, sulfonated AlPc, disulfonated, tetrasulfonated derivatives, sulfonated aluminum naphthalocyanines, naphthalocyanines with or without metal substitution and with or without various substitutions, chlorophyllis, bacteriochlorophyll A, anthracenediones, anthrapyrazoles,Aminoanthraquinones, phenoxazine dyes, phenothiazine derivatives, chalcogenapyrylium dyes, cationic selena and tellurapyrylium derivatives, ring-substituted cationic PCs, pheophorbide derivatives, natural porphyrins, hematoporphyrin, ALA-induced protoporphyrin IX, endogenous metabolic precursors, 5-aminolevulinic acid, benzonaphthoporphyrazine, cationic iminium salts, tetracycline, lutetium texaphyrin, Examples of suitable dyes include texaphyrin, tin-ethio-purpurin, porphycene, benzophenothiazinium, eosin, erythrosine, cyanine, merocyanine 540, selenium-substituted cyanine, flavin, riboflavin, proflavin, quinone, anthraquinone, benzoquinone, naphthaldiimide, Victoria blue, toluidine blue, dianthoquinone (e.g., hypericin), fullerene, rhodamine, and photosensitive derivatives thereof.

[0041] An advantage of using light rather than heat is that there is a lower risk of thermal tissue damage (cell death). Another advantage of using light rather than heat to achieve device-tissue bonding is that complications due to uneven heat distribution may be reduced or eliminated.

[0042] In addition, the use of wavelength-specific absorbers, such as chromophores, allows for differential absorption between the chromophore-containing region and the surrounding tissue. One advantage is selective absorption of radiation by the target without the need for precise focusing. Furthermore, the high absorption of the chromophore-containing region allows for the use of lower power levels, reducing tissue damage.

[0043] Stent-containing devices include self-expanding devices and balloon-expandable devices. Stent components of stent-containing devices can be metallic or polymeric, biostable, or bioabsorbable. In certain embodiments, stent components are formed from metals selected from stainless steel, nitinol, titanium, and Elgiloy (an alloy containing cobalt, chromium, and nickel), among others. In certain other embodiments, stent segments are formed from biodegradable polymers selected from polylactide, polyglycolide, poly(lactide-co-glycolide), polycaprolactone, and polydioxanone, among others. In certain further embodiments, stent segments are formed from biodegradable metals, such as iron, iron alloys, magnesium, and magnesium alloys, among others.

[0044] The stent struts can be coated with a coating material that does not span the cells between the struts (coated stent).The stent struts can be coated with a coating material that spans the cells between the stent struts (covered stent).

[0045] As previously mentioned, stent-containing devices used in accordance with the present disclosure include bare stents, drug-eluting stents (which may have a drug-eluting coating), and stents partially or completely covered with a covering material. Covering materials include nonporous covering materials (e.g., solid thin films) and porous covering materials, including porous thin films (e.g., expanded polytetrafluoroethylene or ePTFE) and fiber-based coverings. In this regard, stent coverings used in the present disclosure can be formed using a variety of fiber-based construction techniques and include, for example, woven and nonwoven stent coverings (e.g., knitted, braided, coiled, randomly wound, spunbonded, etc.).

[0046] Coating materials can be selected from a variety of synthetic and natural polymers. Useful polymers for forming coatings on devices, including stents, can be selected from, among others: (a) polysiloxanes (i.e., silicones), including, among others, polydimethylsiloxane (PDMS); (b) fluoropolymers, including homopolymers and copolymers of C2-C8 alkenes in which one or more hydrogen atoms have been replaced with fluorine, such as, among others, polytetrafluoroethylene (PTFE), polyvinylidene fluoride (PVDF), and poly(vinylidene fluoride-co-hexafluoropropene) (PVDF-HFP); (c) polyamides, including, among others, nylon; (d) polyesters, including, among others, polyethylene terephthalate; (e) polyurethanes, including, among others, polyether-based polyurethanes, polycarbonate-based polyurethanes, and polyalkene-based polyurethanes (e.g., polyisobutylene-based polyurethanes); and (f) C2-C8 olefins. (8) Homopolymers and copolymers of alkenes, such as polyolefin homopolymers and copolymers, including, among others, polyethylene and polypropylene; (g) polyoxyalkylenes, including homopolymers of trioxane (e.g., polytrioxane, also known as polyoxymethylene or acetal) and copolymers of trioxane (e.g., copolymers of trioxane and dioxane); and (h) block copolymers comprising one or more polystyrene blocks and one or more polyalkene blocks, such as styrene copolymers, including, among others, poly(styrene-b-isobutylene-b-styrene) (SIBS) or poly(styrene-b-ethylene / butylene-b-styrene) (SEBS), e.g., alkene-styrene copolymers.

[0047] The fiber width (e.g., diameter of a circular fiber) of a fiber-based stent coating can vary. In certain embodiments, a device including a stent of the present disclosure can have a fiber width ranging from 1 μm to 500 μm (e.g., ranging from 1 μm to 2.5 μm to 5 μm to 10 μm to 25 μm to 50 μm to 100 μm to 250 μm to 500 μm), among other values ​​(i.e., a range between any two of these values). In certain embodiments, the fibers can include surface features, for example, to increase the surface area of ​​the fibers and, therefore, the contact area between the fibers and the coating of binder material.

[0048] Porous stent coatings according to the present disclosure can also have a wide range of pore sizes. In various embodiments, devices including stents of the present disclosure can have area pore sizes ranging from 1 μm to 100 μm (e.g., from 1 μm to 2.5 μm to 5 μm to 10 μm to 25 μm to 50 μm to 100 μm) (i.e., a range between any two of these values).

[0049] The bonding material can be bonded to devices, including stents, in a variety of ways. For example, the bonding material can be applied as a coating to all or a portion of a bare stent component, to all or a portion of a coated stent (e.g., a drug-eluting stent), or to all or a portion of a partially or fully coated stent. As another example, the bonding material can be impregnated and mixed into all or a portion of a stent component material (especially a polymeric stent material), impregnated and mixed into all or a portion of a stent coating material, impregnated and mixed into all or a portion of a stent covering material, or a combination thereof. As another example, a layer (e.g., a sheet) of bonding material can be laminated onto all or a portion of a stent component material, onto all or a portion of a stent coating material, onto all or a portion of a stent covering material, or a combination thereof. The stent covering material can be coated, impregnated, and / or laminated with the bonding material before or after the stent covering material is bonded to the stent component.

[0050] The bonding material may be present along the entire length of the stent-containing device, for example, or may be present only at specific points along the length of the stent-containing device, for example, attached to the ends of the stent-containing device, thereby allowing the majority of the stent-containing device to be free of bonding material, which, among other benefits, reduces bonding material consumption.

[0051] The bonding material can be impregnated and / or coated onto another material using a variety of techniques, which may be selected from, for example, dipping techniques, spraying techniques, spin coating techniques, web coating techniques, electrostatic techniques, and application techniques in which the bonding material is selectively applied to certain areas of the device, including the stent, but not others, for example, by use of a suitable application device, such as a sprayer, brush, roller, pen, or printer (e.g., screen printing device, inkjet printer, etc.).

[0052] If the bonding material does not adhere to the stent, the (optional) covering material, or both, an intermediate layer that bonds to (a) the bonding material and (b) the stent, the (optional) covering material, or both, can be used, e.g., as a tie layer. In certain embodiments, the intermediate layer can be transparent to the energy applied to the bonding material.

[0053] As previously mentioned, various embodiments of the present disclosure relate to devices in which the stent component includes a stent that may be, for example, metallic or polymeric, biostable or bioabsorbable, self-expanding or balloon-expandable.

[0054] In some embodiments, the stent components can be formed entirely from bonded materials. In some embodiments, the stent components are partially or completely coated or impregnated with the bonding material.

[0055] In some embodiments, the bonding material can be bioabsorbable, e.g., leaving only the stent component and / or optional covering material after incorporation (e.g., if the stent or optional covering material is biostable or bioabsorbable). As noted above, the bioabsorption rate can be tailored, e.g., from days to weeks to months.

[0056] In some embodiments, stent component elements (e.g., stent wires, stent struts, etc.) can be coated with a bonding material such that the cells remain open. One particular embodiment is shown in Figure 1, which shows a stent 100 whose structural elements are completely coated with a bonding material 120, while the stent cells 110c remain open.

[0057] In other embodiments, the bonding material can coat the stent cells. A particular embodiment is shown in Figure 2, which is a schematic diagram of a stent 100, whose stent cells are coated with bonding material 120. The bonding material may be present, for example, only on the outer (abluminal) surface of the structural element 110, only on the inner (luminal) surface of the structural element 110, or may completely enclose the structural element 110.

[0058] In some embodiments, the stent is partially coated or impregnated with a bonding material. One particular embodiment is shown in FIG. 3, which shows a stent 100 with bonding material 120 applied to structural elements 110 only at the ends of the stent. Another particular embodiment is shown in FIG. 4, where bonding material 120 is applied to structural elements 110 at intervals along the length of the stent 100. In the embodiment shown in FIGS. 3 and 4, bonding material 120 spans at least a portion of the stent cells. Bond material 120 may be present, for example, only on the outer (abluminal) surface of structural elements 110, only on the inner (luminal) surface of structural elements 110, or may completely enclose structural elements 110. In other embodiments, the structural elements are coated with bonding material such that the stent cells remain open.

[0059] In some embodiments, a device is provided that includes a stent, wherein the stent components are partially or completely coated with a coating material. As with others, the stent components can be metallic or polymeric, biostable or bioabsorbable, self-expanding or balloon-expandable. The coating material can be biostable or bioabsorbable, porous or non-porous. The coating material can be a woven or nonwoven fiber structure. The coating material can completely or partially coat the stent components.

[0060] The partially or fully covered stent can then be partially or fully coated with a bonding material. For example, the partially or fully covered stent can be coated with bonding material on the exterior (abluminal) surface but not the interior (luminal) surface. The partially or fully covered stent can be coated with bonding material at or near the ends of the stent or in other strategic areas. The partially or fully covered stent can be coated with bonding material on the covering but not on the stent components.

[0061] One particular embodiment is shown schematically in Figure 5A, in which only the central region of the stent section is coated with coating material 130. Bonding material 120 is applied to structural elements 110 at the ends of the stent in areas not covered by coating material 130. In the illustrated embodiment, bonding material 120 spans the stent cells, in which case bonding material 120 may be present, for example, only on the outer (abluminal) surface of structural elements 110, only on the inner (luminal) surface of structural elements 110, or may completely enclose structural elements 110. In other embodiments, the structural elements are coated with bonding material such that the stent cells remain open.

[0062] Another specific embodiment is shown schematically in Figure 5B, in which the entire stent is coated with coating material 130 and bonding material 120 is applied to the coating material at the ends of the stent. In certain embodiments, the coating material can be formed from a material that is permeable to the applied bonding energy, such that bonding energy from an energy source disposed luminally relative to the coating material (i.e., inside the stent) can reach the bonding material on the outer surface (abluminal side) of the coating material. If an intermediate layer (not shown) is disposed between bonding material 120 and coating material 130, the intermediate material can likewise be formed from a material that is permeable to the applied bonding energy.

[0063] 6, the coating material 130 can have openings of various sizes that allow energy to pass through the coating and activate the bonding material 120. The bonding material 120 can span the holes as shown, or in some embodiments, can be applied to all or a portion of the coating material 130. In some embodiments, the structural elements 110 are coated with the bonding material, but the stent cells remain open.

[0064] In some embodiments, the bonding material is applied to a site separate from the stent-containing device, which may be bonded to the bonding material upon delivery (see, e.g., FIGS. 1-6) or may not include the bonding material upon delivery. In these embodiments, the bonding material may be applied to tissue followed by delivery of the stent-containing device, or the stent-containing device may be delivered followed by application of the bonding material. After introduction of the device and bonding material, the device and bonding material are irradiated using an appropriate energy source.

[0065] The independently applied bonding material can be applied in solid or liquid form, or a combination thereof. If independently applied in solid form, the bonding material can be in the form of a patch, a thin film, or a tape attached to a device suitable for radial expansion (e.g., a balloon) that can be pressed against the lumen wall by expanding the device (e.g., by inflating the balloon). If independently applied in liquid form, the bonding material can be in the form of, for example, a liquid, paste, or gel (e.g., an organic or aqueous liquid, paste, or gel containing a solder material and / or a photosensitive dye) that is applied using a suitable device, such as a catheter. For example, the bonding material can be applied to a body lumen via a catheter before deployment of a stent-containing device, or the bonding material can be attached to a stent-containing device after deployment via a catheter. The bonding material and stent-containing device are then irradiated by an appropriate energy source, for example, using an energy source integrated into the application catheter or another means.

[0066] In certain embodiments, the bonding material can be applied to a body lumen without implanting a device, including a stent. If applied in a solid form, the bonding material can be in the form of a patch, or a thin film or tape, attached to a device suitable for radial expansion, for example. Once pressed against the lumen wall, the bonding material can be bonded to the wall by exposure to energy. This can be used, for example, to repair and / or close a luminal breach. In other embodiments, a liquid form of the bonding material can be used to repair and / or close a luminal breach.

[0067] As previously mentioned, a variety of energy sources can be utilized in the present disclosure. In some embodiments, the energy source is provided with its own separate device, while in other embodiments, the energy source can be incorporated into the delivery device. In various embodiments, the energy source is adapted to direct energy radially outward from the side of the device. In certain cases, the energy source can be rotatable (e.g., manually or mechanically) to direct energy in a circular fashion (i.e., 360-degree illumination). Circular illumination can also be achieved by directing energy from the entire periphery of the device (e.g., via multiple LEDs, multiple optical fibers, etc.). In certain embodiments, the energy is directed from the energy source through a permeable material, such as a permeable hollow catheter shaft or a permeable balloon, among others.

[0068] In embodiments in which the energy source is provided with its own separate device, the energy source may be incorporated into, for example, an over-the-wire or monorail catheter, or the energy source may be inserted, for example, through a lumen of a delivery catheter. In one embodiment illustrated in Figure 10, the light emitting device 340 may include multiple light emitting elements 340e, such as multiple LEDs or fiber optic tips, that radiate outward from the device.

[0069] As an example of an embodiment in which the energy source is incorporated into the delivery device, the energy source can be incorporated into the guidewire 345, as shown in FIG. 11, for example, by incorporating a light-emitting fiber optic core 345e into the guidewire. Light from the core can be dispersed radially at the point where the light exits the core using appropriate optics. In certain other embodiments, the energy pathway is incorporated into the delivery catheter. For example, the delivery catheter can include multiple LEDs or fiber optic tips emitting outward from the delivery catheter. In some embodiments, the energy source is incorporated into a balloon catheter, in which case the energy source 360e can be attached to the distal side of the balloon 365 of the balloon catheter 360, as shown in FIG. 12. The energy source can also be located proximal to the balloon or inside the balloon. If located inside the balloon, the balloon is formed from a material that is transparent to the energy being applied. One advantage of incorporating the energy source inside the balloon is that the balloon helps to keep the energy source centered within the body lumen. Of course, mechanisms other than a balloon, such as a delivery sheath or stent, can also be used to center the energy source.

[0070] One embodiment of a procedure for delivering a stent according to the present disclosure will now be described with reference to FIGS. 7A-7C. First, a guidewire 310 is placed within a body lumen 200, as shown in FIG. 7A. A stent is then delivered over the guidewire 310. For example, a stent can be delivered using a delivery device known in the art of stent delivery, such as a device in which a stent is placed between an outer catheter sheath 330 and an inner catheter member 320 and delivered to a delivery site when the sheath 330 is retracted, resulting in self-expansion of the stent, as shown in FIG. 7B. However, unlike other known procedures, the stent in this embodiment has stent elements 110 coated with a bonding material 120 at the ends of the stent. In the illustrated embodiment, after the stent is delivered, the delivery catheter is retracted and a device 340 including energy-emitting elements 340e is introduced over the guidewire 310 to activate the bonding material 120 and secure the stent to the tissue of the body lumen 200. In other embodiments, the energy source can be included in the delivery catheter.

[0071] Another embodiment of a procedure for delivering a stent according to the present disclosure will now be described with reference to FIGS. 8A-8C. In this embodiment, a first catheter 350 having a first balloon 355 is positioned within a body lumen 200, which may be a blood vessel, as shown in FIG. 8A to block flow within the body lumen 200. Next, as shown in FIG. 8B, a stent 100 mounted on a second catheter 360 advanced through the first catheter 350 is delivered to the site. In the illustrated embodiment, the entire length of the stent 100 comprises a bonding material. As shown in FIG. 8C, the second catheter 360 has a second balloon 365 that, upon inflation, expands the stent 100 within the body lumen 200. After stent expansion, an energy source within the balloon 365 of the second catheter 360 can be used to activate the bonding material of the stent 100, allowing the stent to be secured to the tissue of the body lumen 200. In other embodiments, the energy source is introduced via a separate device.

[0072] Yet another embodiment of a procedure for delivering a stent in accordance with the present disclosure will now be described with reference to FIG. 9 . In this embodiment, a self-expanding or balloon-expandable stent having stent elements 110 and stent covering 130 is delivered to a body lumen 200 using an appropriate delivery technique (e.g., via a catheter with a retractable sheath, a balloon catheter, etc.). A catheter 370 is then used to deliver a bonding material to the stent. For example, as shown in FIG. 9 , bonding material 120 can be delivered in liquid form from one or more lumens 3701 of delivery catheter 370. After application of bonding material 120, the stent and tissue are irradiated with a suitable energy source 370e, which in this embodiment is provided on catheter 370, thereby activating bonding material 120 and bonding the stent to the tissue of body lumen 200. In other embodiments, the energy source is inserted by a separate device.

[0073] In certain embodiments, devices including stents of the present disclosure may include various additional agents, including, among other possible agents, therapeutic agents and imaging agents, which may be, for example, included in or incorporated into a coating on all or a portion of the stent component material, included in or incorporated into a coating on all or a portion of the binder material, and / or included in or incorporated into a coating on all or a portion of the optional covering material.

[0074] The terms "therapeutic agent," "drug," "bioactive agent," "medication," "pharmaceutically active agent," and other related terms may be used interchangeably herein. Therapeutic agents include anti-restenotic agents, anti-hyperplasic agents, and anti-granulation tissue agents. Therapeutic agents may be used alone or in combination.

[0075] Additional agents for use with devices, including stents, of the present disclosure also include imaging agents including: (a) contrast agents for use with X-ray fluoroscopy, including, inter alia, metals, metal salts and oxides (particularly bismuth salts and oxides), and iodide compounds; (b) contrast agents for use with ultrasound imaging, including organic and inorganic echogenic particles (i.e., particles that result in an increase in reflected ultrasound energy) or organic and inorganic echolucent particles (i.e., particles that result in a decrease in reflected ultrasound energy); and (c) contrast agents for use with magnetic resonance imaging (MRI), including contrast agents containing moieties with relatively large magnetic moments, e.g., God(III), Mn(II), Fe(III), and compounds (including chelates) containing these, e.g., gadolinium ion chelated with diethylenetriaminepentaacetic acid.

[0076] In various embodiments, the device, including the stent, can include from less than 1 wt% to more than 50 wt% of one or more of the aforementioned additional agents. In another aspect of the present disclosure, a medical kit useful for a stent-containing device procedure is provided. The medical kit may include all or a subset of all components useful for performing the procedure. For example, the medical kit may include any combination of two, three, or more of the following items: (a) a stent-containing device, with or without an attached bonding material; (b) a bonding material, e.g., in liquid form or in solid form; (c) one or more medical devices (e.g., a guidewire, a stent delivery device, and / or a device used to apply the bonding material); (d) an energy source (e.g., in a standalone unit or coupled to a surgical instrument); (e) suitable packaging; and (f) printed material containing one or more of (i) storage information and (ii) instructions on how to implant the stent-containing device in a subject.

[0077] While various embodiments have been specifically illustrated and described herein, it will be understood that modifications and variations of the present disclosure are encompassed by the above teachings and within the purview of the appended claims without departing from the spirit and intended scope of the invention.

Claims

1. A medical device comprising: (a) a stent structure having opposite ends, a central region therebetween, and a plurality of elements extending circumferentially about the stent structure, the plurality of elements being connected to one another so as to define a plurality of cells, each cell including sides surrounding an open space; (b) a coating or covering material disposed on the stent structure; and (c) a bonding material bonded to the plurality of elements, the bonding material being bonded to the plurality of elements by coating at least a portion of the plurality of elements or by the bonding material being integral with at least a portion of the plurality of elements; the bonding material does not span the cells between the elements; the medical device is configured to bond to tissue when the bonding material is exposed to an energy source; the energy source is a light energy source; A medical device, wherein the bonding material comprises a tissue solder material comprising a protein and a photosensitive dye, the tissue solder material being selected from albumin, collagen, elastin, fibrinogen, nanopeptide, or a combination of two or more thereof.

2. The medical device of claim 1 , wherein the coating or covering material covers only a portion of the stent structure.

3. The medical device of claim 2 , wherein the bonding material is bonded to the plurality of elements in areas of the stent structure that are not covered by the coating or covering material.

4. 4. The medical device of claim 2 or 3, wherein both ends of the stent structure are not covered by the coating or covering material.

5. The medical device of any one of claims 2 to 4, wherein the coating or covering material includes a plurality of openings in which the stent structure is not covered by the coating or covering material.

6. 6. The medical device of claim 1, wherein the bonding material is bonded to the elements located at opposite ends of the medical device and is not bonded to the elements along a central region of the medical device.

7. 2. The medical device of claim 1, wherein the coating or covering material is sufficiently transparent to energy from the energy source such that when the energy source is positioned luminally relative to the coating or covering material, the energy source can be used to activate a bonding material positioned abluminally relative to the coating or covering material.

8. The medical device of any one of claims 1 to 7, wherein the medical device is self-expanding or balloon-expandable.

9. The coating or covering material is (a) polysiloxane, (b) a fluoropolymer; (c) polyamide, (d) polyester, (e) polyurethane, (f) polyolefin polymers; (g) a polyoxyalkylene, or (h) a styrene copolymer, or (i) The medical device according to any one of claims 1 to 8, comprising any combination of (a) to (h).

10. The medical device of any one of claims 1 to 9, further comprising an intermediate layer disposed between the bonding material and the coating or covering material.

11. The medical device of any one of claims 1 to 10, wherein the medical device is deliverable between the outer sheath and the inner member.

12. The medical device of any one of claims 1 to 11, wherein the medical device further comprises a therapeutic agent, an imaging agent, or both.

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