Ceramic barrier for reducing metal ion elution from metal-based coronary stents and a method of manufacturing the same

Abstract

The present invention relates to metal-based coronary stents designed to reduce or eliminate the release of metal ions into the physiological environment. The invention further provides a method of manufacturing such stents, wherein a metal alloy tube is laser-cut to form a stent platform comprising longitudinal and circumferential struts, followed by cleaning, electropolishing, heat-treatment, passivation and ultrasonic ethanol cleaning. The processed platform is coated with a ceramic layer of titanium nitride having a uniform thickness in the range of 200-3000 nm using physical vapor deposition. The titanium nitride coating acts as a biocompatible ion-barrier, improving hemocompatibility and reducing complications such as restenosis, inflammation, thrombogenicity, and long-term metal ion elution, while maintaining mechanical integrity and radial strength required for vascular deployment.

Description

[0001] 816-356

[0002] CERAMIC BARRIER FOR REDUCING METAL ION ELUTION FROM METAL¬

[0003] BASED CORONARY STENTS AND A METHOD OF MANUFACTURING THE SAME

[0004] FIELD OF INVENTION

[0005] The present invention relates to the field of biomedical engineering. The present invention relates to metal-based coronary stents, which are intraluminal endoprosthesis devices implanted into vessels within the body, such as blood vessels, to support and hold open the vessels, or to secure and support other endoprosthesis in vessels. In particular, the present invention relates to a method for reducing release of metal ions from metal-based coronary stents. The present invention also provides a method for producing these metal-based coronary stents.

[0006] BACKGROUND OF THE INVENTION

[0007] In India, the prevalence of coronary artery disease (CAD) is increasing at an alarming rate, necessitating expedient management strategies. CAD manifests when the coronary arteries become occluded with fatty deposits, known as plaque. This plaque gradually accumulates within the artery walls, leading to narrowing and potentially causing shortness of breath, chest pain, or heightened risk of myocardial infarction. According to the National Interventional Council, CAD disproportionately affects younger individuals in India, as 12.6% of interventions are performed on patients under the age of 40.

[0008] For the management of CAD, several approaches exist, including percutaneous transluminal coronary angioplasty, coronary stenting, and coronary artery bypass grafting. Of these, coronary stenting has emerged as the most popular option due to its superior performance, minimal invasiveness, and reduced risk profile. Coronary stents are typically constructed from metal alloys and are introduced in a crimped state on a balloon catheter into the lumen of the diseased artery.

[0009] Restenosis, or the recurrence of arterial narrowing, after balloon angioplasty is caused by a combination of factors, including early elastic recoil, late negative remodeling or vessel shrinkage, and neointimal formation. The initial elastic recoil occurs immediately due to the passive recoil of 816-356 the elastic media. Later, negative remodeling takes place due to increased collagen in the extracellular matrix and thickening of the adventitia. Coronary stenting with Bare Metal Stents (BMS) helps reduce the early elastic recoil and late negative remodeling. However, BMS does not prevent the growth of neo intimal tissue, which can lead to in-stent restenosis, a major limitation of BMS.

[0010] Prior research indicates that the injury caused by stent implantation triggers a healing vascular response, resulting in neointimal formation. Excessive neointimal tissue growth can re-narrow the lumen, leading to in-stent restenosis. Drug-eluting stents (DES) have been shown to reduce restenosis and need for repeat procedures compared to bare-metal stents (BMS). However, the increased risk of late stent thrombosis associated with DES has dampened enthusiasm for their widespread adoption.

[0011] The selection of biomaterials for coronary stent segment has been challenging due to stringent requirements of blood compatibility. Consequently, coatings can be employed to enhance the blood compatibility, while the substrate material can be chosen to provide the necessary structural integrity.

[0012] Prior research using in-vitro and animal models has demonstrated promising results for coatings on vascular devices. This has created an interest of their use for specific applications, particularly in intravascular device segment. The key challenge in this area is ensuring that the coating maintains strong adhesion even when the substrate undergoes moderate plastic deformation. This feature allows many balloon-expandable devices, such as vascular stents, to be coated with titanium nitride.

[0013] Titanium Nitride is a hard-ceramic material that is often used as a coating on metal alloys to improve the substrate’s surface properties. It has a low coefficient of friction and corrosion rates, making it suitable for applications where friction, wear, and erosion are important design considerations.

[0014] US patent no. 5,837,313 outline a method for coating an implantable, open-lattice metal stent prosthesis. This involved applying multiple thin layers of a coating composition containing a solvent mixture of uncured polymeric silicone material, cross linker, and potentially finely divided biologically active particles of controlled size. The coatings were then cured in place, and the 816-356 coated, cured prostheses were sterilized using a process that included argon gas plasma pretreatment and exposure to gamma radiation, electron beam, ethylene oxide, or steam.

[0015] US patent no. 6,153,252 describe a process for coating stents with a first and second surface and passages between them, in order to prevent blockage and bridging of the passages. The process involved contacting the stent with a liquid coating solution containing a film-forming biocompatible polymer, under conditions that allow the polymer to coat at least one surface of the stent while maintaining a fluid flow through the passages, sufficient to prevent the polymer from substantially blocking the passages. It employs a biocompatible polymer. However, polymer coatings are not the preferred choice for coronary stent applications due to risk of late stent thrombosis.

[0016] WO 2002026281 Al reveal that medical devices, especially implantable ones, can be coated with biocompatible materials to minimize or significantly reduce the biological organism's response to the device's introduction. These coatings can incorporate therapeutic drugs, agents, or compounds that further mitigate the organism's reaction. Various materials and coating techniques may be employed to maintain the drugs, agents, or compounds on the medical device until it is delivered and positioned.

[0017] US publication no. 2010 / 0055145 Al describe a drug-eluting stent with a metal body. The outer surfaces of the stent had been treated to improve the adhesion of a biodegradable polymer coating. This coating, containing a drug, was applied to the treated outer surfaces. The coating thickness was such that the drug and the polymer were completely released from the stent body over a 6 to 12-month period.

[0018] US patent no. 10,653,820 disclose a coated coronary stent comprising a stent; a plurality of layers deposited on said stent to form said coronary stent; wherein at least one of said layers comprises a bio absorbable polymer and at least one of said layers comprises one or more active agents; wherein at least part of the active agent is in crystalline form. However, the document uses a bio-absorbable polymer. Polymer coating are not preferred in coronary stent application due to late stent thrombosis.

[0019] Muhammad Ahmed Ali Fahim el al [Long-term outcomes of titanium-nitride-oxide coated stents and drug-eluting stents in acute coronary syndrome: A systematic review and meta-analysis. World J Cardiol 2024 May 26; 16(5): 293-305] discloses meta-analysis of titanium-nitride-oxide coated 816-356 stents. Stephan Windecker el al [Stent Coating With Titanium-Nitride-Oxide for Reduction of Neointimal Hyperplasia. Circulation August 21, 2001. 930] discloses that titanium-nitride-oxide coating significantly reduces neointimal hyperplasia in stainless steel stents. However, there are several disadvantages of titanium-nitride-oxide on stents. The ion barrier of titanium-nitride-oxide coating is partial because of which oxide phase permits leakage. The titanium-nitride-oxide coating is prone to microcracking. Further, titanium-nitride-oxide degrades to TiCh over time. Also, titanium-nitride-oxide has moderate thrombogenicity due to oxide-mediated adhesion.

[0020] Considering the shortcomings of existing vascular stent devices, there is an urgent need for a method of minimizing metal ion elution from metal-based vascular stents and a method of manufacturing the same. Specifically, there is a requirement for a coronary stent device that can mitigate the complications of restenosis and late stent thrombosis, as well as reduce the issues of metal ion elution post implantation.

[0021] OBJECTS OF THE INVENTION

[0022] An objective of the present invention is to provide a method for reducing or eliminating elution of metal ions from a metal-based stent by coating the stent with a ceramic material.

[0023] Still another objective of the present invention is to provide a metal-based stent having a coating of titanium nitride that mitigates the complications of restenosis and late stent thrombosis, as well as reduces or eliminates the elution of metal ions.

[0024] Another objective of the present invention is to provide a method for manufacturing a titanium nitride-coated stent using a laser-cut metal stent platform and a titanium nitride coating.

[0025] Yet another objective of the present invention is to provide a method for producing metal-based coronary stents having reduced or no release of metal ions.

[0026] These and other objects and advantages of the present subject matter will be apparent to a person skilled in the art after consideration of the following detailed description taking into consideration accompanying drawings in which preferred embodiments of the present subject matter are illustrated. 816-356

[0027] SUMMARY OF THE INVENTION

[0028] An aspect of the present invention provides a metal-based stent comprising an elongate stent wall having a uniform thickness and a plurality of slots comprising longitudinal struts and circumferential struts and a coating of a ceramic material having a thickness in the range of 200 - 3000 nm covering the surface of the stent wall and the plurality of slots, wherein the ceramic material is titanium nitride, wherein the coating of titanium nitride is of uniform thickness throughout its coverage of the entire surface of the stent wall and the plurality of slots and reduces or eliminates elution of metal ions from the stent.

[0029] Another aspect of the present invention provides a method for reducing or eliminating elution of metal ions from a metal-based stent comprising: i. laser cutting a metal alloy tube to obtain a metal-based stent platform; ii. cleaning and inspecting the stent platform; iii. electropolishing the stent platform obtained in step (ii); iv. heat-treating the stent platform obtained in step (iii); v. passivating the stent platform obtained in step (iv); vi. cleaning the passivated stent platform obtained in step (v); vii. ultrasonic cleaning the platform obtained in step (vi) with ethanol to obtain a stent; and viii. coating the stent with a ceramic material by physical vapor deposition method; wherein the ceramic material is titanium nitride having a layer thickness in the range of 200 -3000 nm, wherein coating the metal-based stent with titanium nitride reduces or eliminates elution of metal ions from the metal-based stent.

[0030] The intent of this summary is not to be a comprehensive description of the claimed subject matter, but rather to provide a short overview of some of the subject matter's functionality. Other systems, methods, features and advantages here provided will become apparent to one with skill in the art upon examination of the following figures and detailed description. It is intended that all such 816-356 additional systems, methods, features and advantages that are included within this description, be within the scope of any claims.

[0031] BRIEF DESCRIPTION OF ACCOMPANYING DRAWINGS

[0032] The illustrated embodiments of the subject matter will be best understood by reference to the drawings. The following description is intended only by way of example, and simply illustrates certain selected embodiments of composite and processes that are consistent with the subject matter as claimed herein, wherein:

[0033] Figure 1 illustrates the components (102) and manufacturing processes (103) of the titanium nitride (TiN) coated coronary stent system (101).

[0034] Figure 2 illustrates the process chart of TiN coated coronary stent fabrication.

[0035] Figure 3 shows the various stages of TiN coated coronary stent (300).

[0036] Figure 4 shows energy dispersive X-ray spectroscopy (EDS) analysis of result of TiN coated stent surface.

[0037] Figure 5 shows histopathology study result of vessel lumen of distal coronary vessel with stent.

[0038] DETAILED DESCRIPTION OF INVENTION

[0039] A detailed description of various exemplary embodiments of the disclosure is described herein. It should be noted that the embodiments are described herein in such detail as to communicate the disclosure. However, the amount of details provided herein is not intended to limit the anticipated variations of embodiments; on the contrary, the intention is to cover all modifications, equivalents, and alternatives falling within the spirit and scope of the present disclosure.

[0040] The terminology used herein is to describe particular embodiments only and is not intended to be limiting to the invention. As used herein, the singular forms “a”, “an” and “the” are intended to include the plural forms as well, unless the context indicates otherwise. It will be further understood that the terms “comprises” and / or “comprising”, or “includes” and / or “including” or “has” and / or “having” when used in this specification specify the presence of stated features, regions, integers, steps, operations, elements, and / or components, but do not preclude the presence or addition of one 816-356 or more other features, regions, integers, steps, operations, elements, components, and / or groups thereof.

[0041] As used herein, the term “biocompatible” refers to any material that does not cause injury or death to the animal or induce an adverse reaction in an animal when placed in intimate contact with the animal's tissues. Adverse reactions include inflammation, infection, fibrotic tissue formation, cell death, or thrombosis.

[0042] As used herein, the term “restenosis” refers to re-narrowing of a blood vessel after it has been opened, typically following a procedure like angioplasty or stenting. During the healing process, inflammation caused by angioplasty and stent implant injury often causes smooth muscle cell proliferation and regrowth inside the stent, thus partially closing the flow channel, and thereby reducing or eliminating the beneficial effect of the angioplasty / stenting procedure.

[0043] As used herein, the term “Late stent thrombosis (ST)” refers to the formation of a blood clot within a previously implanted coronary stent, occurring between one month and one year after the procedure.

[0044] The present invention is directed towards a metal-based stent comprising an elongate stent wall having a uniform thickness and a plurality of slots comprising longitudinal struts and circumferential struts and a coating of a ceramic material having a thickness in the range of 200 - 3000 nm covering the surface of the stent wall and the plurality of slots, wherein the ceramic material is titanium nitride, wherein the coating of titanium nitride is of uniform thickness throughout its coverage of the entire surface of the stent wall and the plurality of slots and reduces or eliminates elution of metal ions from the stent.

[0045] In an embodiment of the present invention there is provided a metal-based stent, wherein the metalbased stent is selected from the group consisting of a coronary stent, a urinary stent, a urethral and prostatic stent and a peripheral vascular stent.

[0046] In another embodiment of the present invention there is provided a metal-based stent, wherein the metal-based stent is a coronary stent. 816-356

[0047] In still another embodiment of the present invention there is provided a metal-based stent, wherein the stent is constructed to be deployed in a body to hold a natural duct or tract thereof open for passage of fluids or solids therethrough.

[0048] In yet another embodiment of the present invention there is provided a metal-based stent, wherein the stent is having sufficient rigidity in its deployed expanded state to resist collapse under radial pressure exerted inwardly on the wall of the stent by the wall of the natural duct or tract in which it is deployed.

[0049] In still another embodiment of the present invention there is provided a metal-based stent, wherein the stent is a coronary stent constructed to be implanted in a blood vessel to enhance the flow of blood therethrough.

[0050] In an embodiment of the present invention there is provided a metal-based stent, wherein the diameter of the stent is small to enable the stent wall to be inserted into and traverse a portion of the vascular system of the body to a preselected site within a coronary artery.

[0051] Another embodiment of the present invention provides a method for reducing or eliminating elution of metal ions from a metal-based stent comprising: i. laser cutting a metal alloy tube to obtain a metal-based stent platform; ii. cleaning and inspecting the stent platform; iii. electropolishing the stent platform obtained in step (ii); iv. heat-treating the stent platform obtained in step (iii); v. passivating the stent platform obtained in step (iv); vi. cleaning the passivated stent platform obtained in step (v); vii. ultrasonic cleaning the platform obtained in step (vi) with ethanol to obtain a stent; and viii. coating the stent with a ceramic material by physical vapor deposition method; wherein the ceramic material is titanium nitride having a layer thickness in the range of 200 -3000 nm, wherein coating the metal-based stent with titanium nitride reduces or eliminates elution of metal ions from the metal-based stent. 816-356

[0052] In yet another embodiment of the present invention there is provided a method for reducing or eliminating elution of metal ions from a metal-based stent, wherein the metal alloy is selected from the group consisting of cobalt-chromium-tungsten-metal alloy, stainless steel, nitinol, iron alloy, zinc alloy, Nickel-Titanium alloy, Cobalt-Chromium-Tungsten-Nickel alloy and Magnesium alloy.

[0053] In still another embodiment of the present invention there is provided a method for reducing or eliminating elution of metal ions from a metal-based stent, wherein the metal alloy is cobalt- chromium-tungsten-metal alloy.

[0054] In an embodiment of the present invention there is provided a method for reducing or eliminating elution of metal ions from a metal-based stent, wherein the metal-based stent is selected from the group consisting of a coronary stent, a urinary stent, a urethral and prostatic stent and a peripheral vascular stent.

[0055] In another embodiment of the present invention there is provided a method for reducing or eliminating elution of metal ions from a metal-based stent, wherein the metal-based stent is a coronary stent.

[0056] The present invention is directed towards Titanium Nitride (TiN) coated coronary stent which mitigates the complications of restenosis and late stent thrombosis, reduces the issues of metal ion elution post implantation. To achieve these goals, the coronary stent of the present invention has Titanium Nitride coating on the surface of the metal stent platform. Further, the process for preparing the Titanium Nitride-coated coronary stent entails laser cutting of metal tubes made of alloys such as cobalt-chromium-tungsten-metal alloy, stainless steels, Nitinol, Magnesium alloy, followed by cleaning. The cleaned surface then goes through electro-polishing, heat treatment, and passivation. The process continues with ultrasonic cleaning using alcohol solution. Lastly, the cleaned device is coated with Titanium Nitride using physical vapor deposition technique (PVD).

[0057] With reference to Figure 1, said figure depicts titanium nitride (TiN) coated coronary stent system (101), its components (102) and manufacturing processes. 100 depicts the product architecture, which is the system to component to process level flow down. The TiN-coated coronary stent (104) comprises a metal stent platform (105) and a TiN coating (106). The metal stent platform (105) is manufactured through laser cutting, electro polishing, heat treatment, and passivation (107), while the TiN coating is applied via physical vapor deposition (108). 816-356

[0058] Physical Vapor Deposition (PVD), Chemical Vapor Deposition, and ion implantation are the most widely used techniques for depositing TiN coatings. PVD is a vapor deposition process that can be carried out using vacuum evaporation techniques or sputtering. In sputtering, a source is bombarded in a high vacuum with high-energy inert gas ions, producing a glow discharge or plasma. Atoms from the source are then ejected and accelerated using an external bias towards the substrate to form the coating. Various stages of the manufacturing process of TiN-coated coronary stent are listed in Table 1 and Figure 3.

[0059] Table 1. Various stages of manufacturing process of TiN coated coronary stent

[0060] With reference to Figure 2, said figure depicts the process chart for TiN coated coronary stent manufacturing. The manufacturing of a Titanium Nitride-coated coronary stent involves laser cutting (202) a hardened cobalt-chromium-tungsten-metal alloy tube (201), followed by cleaning (203) and initial inspection (204). The cleaned surface then undergoes electro-polishing (205), heat treatment (206), and passivation (207). The process continues with final cleaning (208), inspection (209), and ultrasonic cleaning using an ethanol solution (210). Finally, the cleaned device is coated with Titanium Nitride through physical vapor deposition (211). The quality assurance / quality control of the coating is performed by thickness and surface roughness measurement of coating on the test coupon coated along with the cardiovascular stents (212). 816-356

[0061] With reference to Figure 3, said figure shows the various stages of the TiN coated coronary stent (300). 301 depicts the laser cut metal stent platform without TiN coating and 302 depicts the TiN coated coronary stent in unmounted configuration. 303 illustrates the TiN coated coronary stent mounted on a delivery system by crimping and 304 is the deployed stent. Table 2 shows the features and comparison with predicate devices. The technical advancement of the present invention lies in TiN being used as a ceramic material for coating of coronary stents. The coating of the coronary stents with TiN reduces or eliminates the leaching of metal ions from bare metal stents and can reduce the complications of in-stent restenosis and late stent thrombosis.

[0062] Table 2: Comparative features of the stent of the present invention and other stents known in the art

[0063] Studies using in-vitro and animal experiments have shown promising results for the TiN coating. This has led to the validation of its use for specific applications, particularly in the intravascular device segment. The main challenge in this area is ensuring the coating maintains strong adhesion even when the substrate undergoes moderate plastic deformation. This feature would enable many balloon-expandable devices, such as vascular stents, to be coated with TiN. This can be extended 816-356 to other ceramics such as diamond-like carbon coating (DLC), and Titanium Aluminum Nitride (TiAlN), for medical devices.

[0064] There are many advantages of the TiN coating compared to a TiNO coating on a metal-based stent. The TiNO coating has partial ion barrier because of which the oxide phase permits leakage, whereas the TiN coating has a complete ion barrier made of dense nitride blocks ions. The TiNO coating is prone to microcracking, whereas TiN coating resists delamination for >50k cycles. TiNO coating shows moderate thrombogenicity due to oxide-mediated adhesion, whereas TiN coating shows low thrombogenicity as nitride repels proteins. Moreover, TiNO degrades to TiO2 over time whereas TiN coating is chemically inert under physiological conditions and hence long-lasting. The TiN coating’s homogeneous nitride structure and mechanical robustness provides a novel, non- obvious solution to TiNO’s limitations, reducing ion-induced complications while ensuring stent longevity.

[0065] Further, the present invention demonstrates many advantages over Vuong-Hung Pham et al [Deposition of titanium nitride (TiN) on Co Cr and their potential application as vascular stent. Applied Surface Science 258 (2012) 2864-2868] which discloses use of TiN-deposited Co-Cr as a vascular stent. The document discloses the study of surface, mechanical, morphological, and cell compatibility properties of flat coupons only, not a stent structure. Further, it does not disclose, measure, or address elution of metal ions. The document does not address ion elution or suitability across body systems. The document merely discloses theoretical potential of TiN-deposited Co- Cr as vascular stent. It does not demonstrate any multi-disease / duct types etc. The document discloses only material science on coupons and measures only coupon hardness / modulus without any real demonstration of stent device or deployed-device mechanics or its testing. The document also does not address manufacturability at actual stent scales or insertion / navigation needs of the actual stents. Furthermore, the document discloses only sputtering of TiN onto flat coupons with basic cleaning. There is no disclosure, suggestion or discussion regarding measurement, or aim of reducing metal ion elution.

[0066] Whereas the present invention describes TiN coating as a barrier to reduce or eliminate metal ion elution which is a major safety / toxicity concern in stents. The metal-based stent of the present invention uses this reduction or elimination in metal ion elution as its fundamental clinical advancement / technical advancement for safer long-term vascular contact, not just improved 816-356 hardness / biocompatibility. Metal ion elution is most critical in coronary (high-contact, blood- exposed) environments. Stents intended for body ducts / tracts must minimize metal ion elution for patient safety. Further, rigidity and mechanical performance in vivo are critical, but only meaningful when metal ion elution is controlled. Such issues are addressed by the stent of the present invention, which offers a real solution to the clinical problem, with data-driven process for reduction.

[0067] EXAMPLES

[0068] EXAMPLE 1

[0069] Method for preparing the coronary stent and coating of TiN on the surface

[0070] For preparing the coronary stent platform, the raw material used was L605 tubes (Cobalt-based Chromium-Tungsten-Nickel alloy) having an outer diameter between 1.6 mm ± 0.010 mm to 2.00 mm ± 0.010 in hard drawn condition.

[0071] The method followed was as provided in Figure 2, which depicts the process chart for manufacture of TiN coated coronary stent. The process involved laser cutting the hardened L605 tubes in a predesigned pattern, followed by cleaning and initial inspection. Laser cutting is a standard method known in the art in the field of stent manufacturing, particularly coronary stents. The finished stent strut thickness was 0.08 mm ± 0.010 mm; and the finished stent strut profile had width 0.08 mm throughout with laser cutting tolerance < 0.006 mm. The cleaning and first inspection of the stent were done using the method known in the art in the field. The cleaned surface of the stent underwent electro-polishing, heat treatment, and passivation. All these methods are known to a person skilled in the art in the field of stent manufacturing. After passivation of the stent, it was given a final cleaning and second inspection by the methods known in the art. After second inspection, the ultrasonic cleaning of stent was done using an ethanol solution.

[0072] Finally, the cleaned stent was coated with Titanium Nitride through physical vapor deposition. 200- 3000 nm TiN coating thickness with a surface roughness of 0.02 to O.lmicron Ra was developed on coronary stents using cylindrical cathodic arc deposition technique. The equipment used were Ultrasonic Cleaning Unit and Cathodic Arc Physical Vapor Deposition Unit (CAPVD). 816-356

[0073] After placement of the stent sample and fixtures into the CAPVD deposition chamber, the chamber was evacuated to a base pressure in the range of 4.5 x 106mbar to 7.5 x 106mbar and heated to a temperature in the range of 300°C to 450°C. A titanium nitride (TiN) coating was deposited under the following process parameters: ■ Titanium cathode current: about 150 A to about 300 A

[0074] ■ Deposition time: about 20 minutes to about 2 hours

[0075] ■ Nitrogen flow rate: about 150 seem to about 300 seem

[0076] ■ Substrate bias voltage: about 30 V to about 50 V

[0077] ■ Substrate current: about 6 A to about 10 A Thus, obtained was a coronary stent having a TiN coating.

[0078] EXAMPLE 2

[0079] TiN coating integrity and trace element analysis on the coronary stent

[0080] The TiN coated stent sample was attached on the specimen holder using suitable SEM vacuum quality adhesive and accelerating voltage was set to 20 kV. The equipment used for the study was as provided in Table 3 and SEM images were obtained.

[0081] Table 3 816-356

[0082] The SEM images are shown in Figure 4. From the results of figure 4, it was observed that the coating remained intact even after multiple crimping and expansion cycles, and no undesirable elements were observed. There were no undesirable elements present in one time crimped and three times crimped stents spectrum.

[0083] It can be inferred from the results that the TiN-coated stent was subjected to repeated crimping and expansion cycles without exhibiting coating peeling or delamination. This confirms the coating’s adhesion strength and structural stability under biomechanical stress, further implying that the ceramic barrier remains intact during deployment. A continuous, defect-free TiN layer is critical to preventing metal ion leaching over the stent’s lifespan. Together, these findings substantiate that the TiN coating provides a durable, impermeable barrier that mitigates metal ion release.

[0084] EXAMPLE 3

[0085] Animal study The study was performed to assess local biological response such as thrombus deposition, inflammation, endothelialisation, neointimal proliferation, necrosis, aneurysm formation and downstream and systemic effects such as embolism, infarction, through evaluation of histology and pathology of TiN coated coronary stent and pertinent tissues / organs at 6 months of implantation.

[0086] Ankamali pigs procured from Division of In-Vivo Models and Testing, Sree Chitra Tirunal Institute for Medical Sciences and Technology, Thiruvananthapuram, Kerala, India, belonging to either sex were randomly selected. Stents were implanted in the coronary arteries, RC and LAD in random order. Table 4 below shows the stent types implanted in different coronary arteries at a time period of 6 months.

[0087] Table 4

[0088] The animals survived the observation period uneventfully and the TiN coated coronary stent under the study were present at autopsy. There was progressive weight gain in all the animals during the observation period. None of the animals included in the study showed any device related adverse clinical symptoms during the study. In general, the blood vessels were well within the normal haematological / biochemical range of the pig population at both implantation and explantation. This indicated that the implanted devices have not adversely affected any of the organ systems of the animals under the study either in TiN coated stent system and bare metal stents (control).

[0089] The animal study here demonstrates that TiN-coated stents exhibit no restenosis and no late stent thrombosis. Since metal ion release (e.g., nickel, chromium) from L605 metal is a known contributor to inflammation, neointimal hyperplasia, and thrombogenicity, the absence of these complications in TiN-coated stents indicates effective suppression of metal ion elution. The ceramic TiN coating acts as a diffusion barrier, isolating the underlying alloy from the physiological environment. EXAMPLE 4

[0090] Histopathology study

[0091] Gross and histopathological evaluation of tissue response to material in end use application study was performed on the TiN coated coronary stent after 6 months and 12 months of implantation.

[0092] Adult female swine heart sample of the Ankamali pigs (procured from Division of In-Vivo Models and Testing, Sree Chitra Tirunal Institute for Medical Sciences and Technology, Thiruvananthapuram, Kerala; CPCSEA approval V-l 101 l(13) / 15 / 2020-CPCSEA-DADT dated 9 October 2020) with coronary stents for 6 months, perfused and immersion fixed in 10% neutral buffered formalin was collected in all cases. The specimen was preserved in 10% buffered formalin and embedded in PMMA and paraffin. The heart was examined and stents were identified in appropriate coronary arteries. The stented segments (coronary blood vessel) were processed for resin embedding. Cross sections of proximal and distal reference segments of host vessel, myocardium of supply areas was processed for paraffin embedding. Histological evaluation was done on thin resin sections from the proximal, middle and distal segments of the stents stained with haematoxylin and eosin.

[0093] The results are shown in Figure 5. It was observed that the left anterior descending (LAD) vessel lumen was present throughout the length of the stented vessel segment. LAD supply area of ventricle myocardium did not reveal any abnormality. The results imply that the vessel lumen was patent throughout and no abnormalities were observed.

[0094] Although embodiments for the present subject matter have been described in language specific to features, it is to be understood that the present subject matter is not necessarily limited to the specific features described. Rather, the specific features and methods are disclosed as embodiments for the present subject matter. Numerous modifications and adaptations of the system / device of the present invention will be apparent to those skilled in the art, and thus it is intended by the appended claims to cover all such modifications and adaptations which fall within the scope of the present subject matter. 816-356

[0095] It will be further appreciated that functions or structures of a plurality of components or steps may be combined into a single component or step, or the functions or structures of one-step or component may be split among plural steps or components. The present invention contemplates all of these combinations. Unless stated otherwise, dimensions and geometries of the various structures depicted herein are not intended to be restrictive of the invention, and other dimensions or geometries are possible. In addition, while a feature of the present invention may have been described in the context of only one of the illustrated embodiments, such feature may be combined with one or more other features of other embodiments, for any given application. It will also be appreciated from the above that the fabrication of the unique structures herein and the operation thereof also constitute methods in accordance with the present invention. The present invention also encompasses intermediate and end products resulting from the practice of the methods herein.

Claims

816-356WE CLAIM:

1. A metal-based stent comprising an elongate stent wall having a uniform thickness and a plurality of slots comprising longitudinal struts and circumferential struts and a coating of a ceramic material having a thickness in the range of 200 -3000 nm covering the surface of the stent wall and the plurality of slots, wherein the ceramic material is titanium nitride, wherein the coating of titanium nitride is of uniform thickness throughout its coverage of the entire surface of the stent wall and the plurality of slots and reduces or eliminates elution of metal ions from the stent.

2. The metal-based stent as claimed in claim 1, wherein the metal-based stent is selected from the group consisting of a coronary stent, a urinary stent, a urethral and prostatic stent and a peripheral vascular stent.

3. The metal-based stent as claimed in claim 1 , wherein the stent is constructed to be deployed in a body to hold a natural duct or tract thereof open for passage of fluids or solids therethrough.

4. The metal-based stent as claimed in claim 1, wherein the stent is having sufficient rigidity in its deployed expanded state to resist collapse under radial pressure exerted inwardly on the wall of the stent by the wall of the natural duct or tract in which it is deployed.

5. The metal-based stent as claimed in claim 2, wherein the stent is a coronary stent constructed to be implanted in a blood vessel to enhance the flow of blood therethrough.

6. The metal-based stent as claimed in claim 1, wherein the diameter of the stent is small to enable the stent wall to be inserted into and traverse a portion of the vascular system of the body to a preselected site within a coronary artery.

7. A method for reducing or eliminating elution of metal ions from a metal-based stent comprising: i. laser cutting a metal alloy tube to obtain a metal-based stent platform; ii. cleaning and inspecting the stent platform; iii. electropolishing the stent platform obtained in step (ii);816-356 iv. heat-treating the stent platform obtained in step (iii); v. passivating the stent platform obtained in step (iv); vi. cleaning the passivated stent platform obtained in step (v); vii. ultrasonic cleaning the platform obtained in step (vi) with ethanol to obtain a stent; and viii. coating the stent with a ceramic material by physical vapor deposition method; wherein the ceramic material is titanium nitride having a layer thickness in the range of 200 -3000 nm, wherein coating the metal-based stent with titanium nitride reduces or eliminates elution of metal ions from the metal-based stent.

8. The method as claimed in claim 7, wherein the metal alloy is selected from the group consisting of cobalt-chromium-tungsten-metal alloy, stainless steel, nitinol, iron alloy, zinc alloy, Nickel-Titanium alloy, Cobalt-Chromium-Tungsten-Nickel alloy and Magnesium alloy.

9. The method as claimed in claim 7, wherein the metal-based stent is selected from the group consisting of a coronary stent, a urinary stent, a urethral and prostatic stent and a peripheral vascular stent.

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