Surface coating for iron bioresorbable stents

Abstract

The invention relates to bioresorbable iron-based stents with an improved degradation and / or an improved biocompatibility. Said stents are coated with a microgalvanic layer. The invention further relates to a process for coating a bioresorbable iron-based stent, and to bioresorbable iron-based stents for use in the treatment of an anomaly or a disease of a body lumen.

Description

[0001] SURFACE COATING FOR IRON BIORESORBABLE STENTS

[0002] TECHNICAL FIELD

[0003] The invention relates to bioresorbable iron-based stents with an improved degradation and / or an improved biocompatibility.

[0004] TECHNICAL BACKGROUND

[0005] Ischemic heart failure is caused by narrowing and occlusion of an artery, and is nowadays one of the leading causes of death worldwide.

[0006] The most efficient treatment of ischemic heart failure is the use of a stent, which will help restoring at best blood flow in the obstructed artery. First-generation stents, which were bare metal stents, had the drawback of triggering modulated inflammation due to “foreign body reaction”. Therefore, a high rate of restenosis (16 to 44%) was observed due to overproliferation of smooth muscle cells. Drug-eluting stents were developed as second generation of stents, and are suitable for delivering different types of drugs. Drug-eluting stents are suitable to limit inflammation and restenosis, in particular by release of cytotoxic antiproliferative and / or anti-inflammatory drugs. However, drug-eluting stents lead to 10% thrombosis, especially late or very late thrombosis.

[0007] The development of new technologies, such as bioresorbable stents, now represents a main area in the interest of researchers. The aim of bioresorbable stents is to provide an artery mechanical support during the healing period and then progressively resorb when stent’s mission is reached.

[0008] The main requirements for a bioresorbable stent are the biocompatibility of the used materials and the released degradation products, the stent ability to maintain mechanical integrity for 3 to 6 months, and the stent ability to be fully degraded in 12 to 24 months.

[0009] Polymer-based biodegradable stents have rather weak mechanical properties. Metal-based stents would be preferred in terms of mechanical properties. Three metals are especially suitable for the manufacture of bioresorbable stents, magnesium, zinc and iron. Magnesium presents a medium biocompatibility and a (too) fast degradation rate. Zinc comprises an unknown biocompatibility and suitable degradation rates. Iron presents a good biocompatibility but a low degradation rate. It would thus be useful to develop processes for accelerating the degradation rate of iron stents. Coating technologies are one of the main techniques to modify the degradation rate of iron stents.

[0010] US20160263287 discloses an absorbable iron-based alloy stent, comprising an iron-based alloy substrate and a degradable polyester in contact with the surface of the substrate. With the degradable polyester, the iron-based alloy is capable of corroding rapidly and controllably within a predetermined period. Degradation of the polyester generates acidic compounds which lower the pH of the stent environment, and accelerate iron corrosion. In such systems, the corrosion rate of the iron-based alloy is inherently dependent on the kinetics of the polymer degradation. Relying on an external factor, such as the acidic molecules generated in situ by polymer degradation, to trigger corrosion limits reliable and reproducible control over the corrosion process, including the control of the corrosion rate.

[0011] Some publications similarly disclose the use of polymer coating for accelerating biodegradation of iron stents (Qi, Y. et al. (2018). “Strategy of metal-polymer composite stent to accelerate biodegradation of iron-based b\oma eria\s'' AC'S applied materials & interfaces, 10(1), 182-192 and Qi, Y. et al. (2019). “Mechanism of acceleration of iron corrosion by a polylactide coating” ACS Applied Materials & Interfaces, 11 (1) 202-218).

[0012] Another way to accelerate biodegradation of iron and iron alloys is to use microgalvanic effect, which may happen when a metal is contacted with another metal. The presence of this other metal triggers the local formation of galvanic conditions, thus accelerating corrosion of the metal which is the lowest in the galvanic series.

[0013] Beaumont Celine discloses the influence of a thin layer of copper and gold deposition on the corrosion speed of an iron-based alloy for its use in bio-resorbable stents (Beaumont, Celine. “Influence d'un depot de cuivre sur la vitesse de corrosion d'un alliage a base de fer pour des applications de stents bioresorbables. » Ecole polytechnique de Louvain, Universite catholique de Louvain, 2019. Prom. : Jacques, Pascal.). The copper and gold deposit on the iron-based sample is shown to act as a galvanic cell increasing metal corrosion rate. However, the corrosion rate slows down when corrosion products start covering the surface. This suggests that the surface coating in this work is unstable and has a limited active surface area.

[0014] WO2007136965 discloses non-bioresorbable stent grafts made of a first metal, which are partly coated with a second metal so as to generate galvanic corrosion of the coated areas in situ. The goal of the system is to generate inflammation at the coated areas, so as to prevent stent graft migration. The type and amount of dissimilar metals are regulated so as to provide a predetermined amount of galvanic corrosion, sufficient to induce the desired amount of inflammation without completely compromising the stent scaffold’s structural properties. The stents are not made of iron, and the galvanic corrosion does not lead to complete degradation of the stent.

[0015] WO2015164028 discloses a bioerodible stent comprising a five-layered laminate. The inner layer may be made of magnesium, zinc or iron or alloys thereof. The intermediate layers may be made of silver. The outer layers may be made of molybdenum, tantalum or tungsten. Galvanic corrosion between outer and intermediate layers first triggers degradation of the outer layers. Then, galvanic corrosion between inner and intermediate layers triggers degradation of the inner layer. The laminate structure does not allow fine tunability of the corrosion rate, and the corrosion may also not be uniform on the length of the stent as several degradation steps must happen before the bodily fluid which serves as electrolyte reaches the intermediate layer / inner layer pair. In addition, the continuous coating and the absence of coupling agent between both metals do not allow finely controlling the coating structure and the subsequent corrosion mechanism, including the corrosion rate.

[0016] Thus, there remains a need to provide new processes for increasing the degradation rate of iron or iron-alloy stents, without affecting their mechanical properties nor their biocompatibility. Advantageously, the coating should even improve the stent biocompatibility. There also remains a need for processes allowing the fine tunability of the degradation process and rate of iron or iron-alloy bioresorbable stents by corrosion.

[0017] SUMMARY OF THE INVENTION

[0018] In this respect, the Inventors have evidenced that the use of a coating comprising a microgalvanic layer comprising nano- or sub-micrometric structures bonded to an organic primer layer allows accelerating the degradation rate of iron-based stents in a highly efficient and tunable manner. The presence of the coating further stabilizes the microgalvanic layer and improves the biocompatibility of the iron-based stents. Finally, the process for coating the stents with the microgalvanic layer comprising nano- or sub-micrometric structures bonded to an organic primer layer may be implemented in very simple, fast and cheap conditions. Said process allows uniform coating of the overall stent surface with the nano- or sub-micrometric structures. Thus, the present invention relates to a bioresorbable iron-based stent, wherein at least part of the stent is coated with a microgalvanic layer comprising nano- or sub-micrometric structures of a conductive material bonded to an organic primer layer, the conductive material of the nano- or sub-micrometric structures exhibiting a Standard Electrode Potential (SEP) higher than that of iron or of the iron alloy.

[0019] In some embodiments, the organic primer layer is formed by a coupling agent, the coupling agent comprising at least two functions, one capable of binding to the iron-based stent surface, and the other capable of binding to the nano- or sub-micrometric structures, the organic primer layer being obtained by contacting the stent and the nano- or sub-micrometric structures in presence of the coupling agent.

[0020] In some embodiments, the bioresorbable iron-based stent is a bioresorbable endovascular or extravascular stent, preferably a bioresorbable endovascular stent.

[0021] In some embodiments, the conductive material of the nanostructures exhibits a SEP higher than -0.44 V versus standard hydrogen electrode.

[0022] In some embodiments, the nano- or sub-micrometric structures of a conductive material are selected from the group consisting of particles, such as spheres, rods, tubes, cages, ribbons, rings, shells, wires, quantum dots and fibers of the conductive material.

[0023] In some embodiments, the nano- or sub-micrometric structures are selected from the group consisting of carbon nanostructures, such as carbon nanotubes, gold nanostructures, such as gold nanoparticles, silver nanostructures, such as silver nanoparticles, platinum nanostructures, such as platinum nanoparticles, palladium nanostructures, such as palladium nanoparticles, and transition metal oxide nanostructures, such as transition metal oxide nanoparticles, preferably gold nanoparticles.

[0024] In some embodiments, the iron-based stent is an iron stent.

[0025] In some embodiments, the iron-based stent is an iron-alloy stent, wherein the iron alloy preferably includes Fe with at least one element selected from the group consisting of: Li, Na, P, S, K, Ca, Ti, Co, Ni, Cu, Ga, Sr, Y, Zr, Nb, Mo, Ag, Sn, I, Cs, Hf, Ba, Ge, B, O, Ta, W, Re, Os, Ir, La, Ce, Sm, Gd, Mn, C, Si, N, Zn, Mg, Pt, Pd and Au.

[0026] In some embodiments, the alloy comprises at least 50 at % iron before coating, preferably at least 60 at % iron, preferably at least 70 at % iron, preferably at least 80 at % iron, preferably at least 90 at % iron, more preferably at least 95 at % iron. In some embodiments, the microgalvanic layer is present on at least 50%, preferably at least 60%, preferably at least 70%, preferably at least 80%, preferably at least 90%, preferably at least 95%, more preferably at least 99%, of the outer surface of the stent.

[0027] In some embodiments, the organic primer layer is obtained from a coupling agent selected from the group consisting of aryldiazonium salts, siloxane compounds, including poly(ethylene glycol) (PEG) containing siloxanes, polyamines, such as poly dopamine (PDA), and polyimines, such as polyethylenimine (PEI), preferably aryldiazonium salts, more preferably 4- cyanobenzenediazonium tetrafluoroborate, 4-ethynylbenzenediazonium tetrafluoroborate, 4- carboxybenzenediazonium tetrafluoroborate, 4-(aminomethyl)benzenediazonium tetrafluoroborate, and / or 4-boronobenzenediazonium tetrafluoroborate, even more preferably 4-cyanobenzenediazonium tetrafluoroborate.

[0028] In some embodiments, the stent is an iron stent, the nano- or sub-micrometric structures are gold nanoparticles, and the organic primer layer is obtained from a coupling agent which is an aryldiazonium salt, preferably 4-cyanobenzenediazonium tetrafluoroborate.

[0029] In some embodiments, the nano- or sub-micrometric structures are functionalized by at least one functionalizing molecule.

[0030] In some embodiments, the functionalizing molecule is selected from the group consisting of an anti-oxidant, a prostacyclin receptor, and a drug, such as an anti-proliferative agent, an antithrombotic drug, a statin-based drug or an anti-inflammation drug, preferably an anti-oxidant.

[0031] In some embodiments, the anti-oxidant is selected from the group consisting of N- acetylcysteine, vitamins, such as vitamin C or E, mitochondria targeted anti-oxidants, such as MitoQ, polyunsaturated fatty acids, such as omega-3 or omega-6, polyphenol, such as flavonoid, and astaxanthine, preferably the anti-oxidant is N-acetylcysteine.

[0032] In some embodiments, the stent is an iron stent, the nano- or sub-micrometric structures are gold nanoparticles functionalized by an anti-oxidant, such as N-acetylcysteine, and the organic primer layer is obtained from a coupling agent which is preferably an aryldiazonium salt, more preferably a 4-ethynylbenzenediazonium salt, such as 4-ethynylbenzenediazonium tetrafluoroborate.

[0033] Another object of the present invention is a process for coating at least part of a bioresorbable iron-based stent, comprising a step of contacting at least part of the bioresorbable iron-based stent with an aqueous solution or suspension comprising nano- or sub-micrometric structures and / or a precursor thereof and with a precursor of an organic primer layer, wherein the nano- or sub-micrometric structures comprise a conductive material with a SEP higher than that of the ion or iron-alloy of the stent.

[0034] In some embodiments, the nano- or sub-micrometric structures precursor is chloroauric acid or chloroplatinic acid.

[0035] In some embodiments, the coupling agent is selected from the group consisting of aryldiazonium salts, siloxane compounds, including poly(ethylene glycol) (PEG) containing siloxanes, polyamines, such as polydopamine (PDA), and polyimines, such as polyethylenimine (PEI), preferably aryldiazonium salts, more preferably 4- cyanobenzenediazonium tetrafluoroborate, 4-ethynylbenzenediazonium tetrafluoroborate, 4- carboxybenzenediazonium tetrafluoroborate, 4-(aminomethyl)benzenediazonium tetrafluoroborate, and / or 4-boronobenzenediazonium tetrafluoroborate, even more preferably 4-cyanobenzenediazonium tetrafluoroborate.

[0036] In some embodiments, the nano- or sub-micrometric structures are functionalized by at least one functionalizing molecule, and the process according to the invention further comprises a step of contacting at least part of the bioresorbable iron-based stent coated by the nano- or submicrometric structures with an aqueous solution comprising the functionalizing molecule, optionally in presence of a coupling agent.

[0037] In some embodiments, the nano- or sub-micrometric structures are gold nanoparticles, the functionalizing molecule is an anti-oxidant, such as N-acetylcysteine, and the precursor of the organic primer layer is preferably 4-ethynylbenzenediazonium tetrafluoroborate.

[0038] In some embodiments, the concentration of the coupling agent in the aqueous solution is comprised between 0.05 mM and 10 mM, preferably between 0.1 mM and 5 mM, even more preferably is about 0.2 mM or about 5 mM.

[0039] In some embodiments, the concentration of the nano- or sub-micrometric structures and / or a precursor thereof in the aqueous solution is comprised between 0.01 mM and 1 mM, preferably between 0.05 mM and 0.2 mM or between 0.05 mM and 0.7 mM, even more preferably is about 0.1 mM or about 0.5 mM.

[0040] Another object of the invention is a process for controlling, preferably for increasing, the degradation and / or the biocompatibility of a bioresorbable iron-based stent, comprising a step of coating the stent with a microgalvanic layer comprising nano- or sub-micrometric structures of a conductive material bonded to an organic primer layer. In some embodiments, the iron-based stent is an iron stent, the nano- or sub-micrometric structures are gold nanoparticles and the organic primer layer is obtained from a coupling agent, wherein the coupling agent is an aryldiazonium salt, preferably 4-cyanobenzenediazonium tetrafluoroborate.

[0041] In some embodiments, the iron-based stent is an iron stent, the nano- or sub-micrometric structures are gold nanoparticles functionalized by an anti-oxidant, such as N-acetylcysteine, and the organic primer layer is obtained from a coupling agent which is preferably an aryldiazonium salt, more preferably 4-ethynylbenzenediazonium tetrafluoroborate.

[0042] Another object of the invention is a bioresorbable iron-based stent according to the invention, or a bioresorbable iron-based stent obtained by a process according to the invention, for use in the treatment of an anomaly or a disease of a body lumen, such as an aneurysm, aortic dissections, or stenosis / thrombosis affecting coronary, peripheral, or renal arteries / veins, and luminal obstructions due to either intrinsic disease or extrinsic pressure in the esophagus, colon, or bile duct.

[0043] FIGURES

[0044] Figure 1: SEM image of Fe-Au-DCN samples in Example 1.

[0045] Figure 2: Average Raman spectrum of over 20 spectra obtained from random spots on Fe-Au- DCN surface in Example 1. The acquisition used a laser wavelength of 638 nm.

[0046] Figure 3: Comparison of IR spectra of Fe-Au-DCN in Example 1 with reference benzonitrile.

[0047] Figure 4: Survey XPS spectra of Fe-Au-DCN in Example 1 with comparison of reference Fe.

[0048] Figure 5: Mass loss observed during a 28-day static corrosion test in Hank’s solution of the Fe- Au-DCN sample of Example 1.

[0049] Figure 6: Cell viability of 3T3 and HUVEC cells in 12.5%, 25%, 50% extracts for 1 day’s incubation of (a-c) 3T3, and (d-f) HUVEC. The results shown are means ± SD of at least three different experiments. Different letters of groups indicated that the difference of the mean is significant at the 0.05 level. P <0.05. PC presents positive control which means the cells is treated with Lysis solution; NC presents negative control which means the cells are cultured in culture medium. Figure 7: (a) High magnification (5.0 kX) SEM picture of the surface of the stent obtained at Example 1. White dots are gold nanoparticles, and grey substrate is iron, (b) Low magnification (27 X) SEM picture of the stent obtained at Example 1 (left-hand side), and EDX pictures (righthand side) for iron and gold, showing the uniform presence of gold on the iron surface.

[0050] Figure 8: Compared corrosion rates in terms of mass loss (%) per day of the coated stent according to the invention and the corresponding non-coated stent.

[0051] Figure 9: Cell culture results on stent surfaces. Scale bars represent 100 pm.

[0052] Figure 10: SERS spectra of samples prepared in Example 6 (Fe-Au-DCC-lmM; Fe-Au-DCC- 2mM; Fe-Au-DCC-5mM; Fe-Au-DCC-NAC-PI-lmM; Fe-Au-DCC-NAC-PI-2mM; Fe-Au- DCC-NAC-PI-5mM).

[0053] Figure 11: SERS spectra of a sample prepared in Example 6 (Fe-Au-DCC-5mM), immediately after the preparation (t=0) and after 2 days, 4 days and 7 days of storage at room temperature (t=2, 4 or 7 days).

[0054] Figure 12: SERS spectra of a sample prepared in Example 6 (Fe-Au-DCC-NAC-5mM - without photo-initiator and without UV exposure) after 1, 5 and 18 hours from preparation (t=l, 5 or 18h).

[0055] Figure 13: SERS spectra of a sample prepared in Example 6 (Fe-Au-DCC-5mM-NAC-10mM - without photo-initiator and without UV exposure) after 1, 5 and 18 hours from preparation (t=l, 5 or 18h).

[0056] Figure 14: SERS spectra of a sample prepared in Example 6 (Fe-Au-DCC-5mM-NAC-20mM- without photo-initiator and without UV exposure) after 1, 5 and 18 hours from preparation (t=l, 5 or 18h).

[0057] Figure 15: XPS S2p spectrum of a sample prepared in Example 6 (Fe-Au-DCC-NAC-PI- 5mM).

[0058] Figure 16: XPS S2p spectrum of a sample prepared in Example 6 (Fe-Au-DCC-NAC-5mM).

[0059] Figure 17: XPS S2p spectrum of a sample prepared in Example 6 (Fe-Au-DCC-5mM-NAC- 20mM).

[0060] Figure 18: Normalized fluorescence intensity of samples prepared in Example 6 (Fe-Au-DDC- 5mM, Fe-Au-DCC-NAC-5mM, Fe-Au-DDC-5mM-NAC-20mM and Fe-Au-DCC-NAC-PI- 5mM) and of a comparative sample (pure Fe disc) over time. Figure 19: ZEISS confocal fluorescence microscope images of samples prepared in Example 6 ((a): Negative control sample; (b): pure Fe disc, (c): Fe-Au-DCC-5mM, (d): Fe-Au-DCC- NAC-PI-5mM, (e): Fe-Au-DCC-NAC-5mM, (f): Fe-Au-DCC-5mM-NAC-20mM). For Figure 19(a),(b),(d),(e),(f) scale bars represent 50 pm and for Figure 19(c) scale bar represents 90 pm.

[0061] Figure 20: ZEISS confocal fluorescence microscope images of samples prepared in Example 6 ((a): Negative control sample; (b): pure Fe disc, (c): Fe-Au-DCC-NAC-PI-5mM, (d): Fe-Au- DCC-5mM-NAC-20mM). Scale bars represent 50 pm.

[0062] Figure 21: ZEISS confocal fluorescence microscope images of samples prepared in Example 6 ((a): pure Fe disc, (b): Fe-Au-DCC-NAC-PI-5mM, (c): Fe-Au-DCC-5mM-NAC-20mM). Scale bars represent 50 pm.

[0063] DETAILED DESCRIPTION OF THE INVENTION

[0064] The invention first relates to a bioresorbable iron-based stent, wherein at least part of the stent is coated with a microgalvanic layer comprising nano- or sub-micrometric structures of a conductive material bonded to an organic primer layer. The iron-based stent is either an iron stent or an iron-alloy stent.

[0065] The iron or iron-alloy of the bioresorbable iron-based stent according to the invention exhibits accelerated corrosion, and thus accelerated biodegradation, thanks to the presence of the microgalvanic layer. Galvanic (or microgalvanic) effect occurs because of the potential difference between the iron or iron alloy of the stent and the conductive material of the nano- or sub-micrometric structures. In physiological conditions, when the stent is deployed in a body lumen, such as an artery, the body fluids, such as serum and / or blood, act as an electrolyte.

[0066] In addition, the bioresorbable iron-based stent according to the invention preferably exhibits an improved biocompatibility compared to the corresponding non-coated iron-based stent. In some embodiments, the coating scavenges the released reactive oxygen species (ROS).

[0067] Another advantage of the bioresorbable iron-based stent according to the invention is that it can be manufactured by a simple process.

[0068] The corrosion process and kinetics of the stent can be finely tuned by selecting the nature and amount of the nano- or sub-micrometric structures and of the organic primer layer. Definitions

[0069] An “iron-based stent” is a stent which is made of iron or of an iron alloy comprising at least 50 at % (atomic percentage) iron.

[0070] A “bioresorbable stent” or a “resorbable stent” is a stent, or a portion thereof, that exhibits substantial mass or density reduction or chemical transformation in physiological conditions. Mass reduction may occur by dissolution of the stent material, by fragmentation of the stent, and / or by galvanic reaction. In other words, a bioresorbable stent is able to resorb in physiological conditions after a certain duration, preferably after the stent’s mission is achieved. The terms “bioerodible” and “bioabsorbable” may be used as synonyms of “bioresorbable” .

[0071] A “biocompatible” device or material is a device or material which is able to perform with an appropriate host response in a specific application. Preferably, the biocompatible device or material does not cause major injury or death to the patient when placed in intimate contact with the patient’s tissues

[0072] An “alloy” is a metallic solid solution or intermetallic compound made by combining two or more elements in which the major alloying element in volume fraction is metallic. An “iron alloy” is an alloy wherein the major alloying element is iron. The iron alloy comprises at least 50 at % iron.

[0073] A “coupling agent” is a compound comprising at least two functions, one of them being able to bind the iron-based stent surface, and the other one being able to bind the nano- or submicrometric structures.

[0074] A “functionalizing molecule” is a molecule that covalently or non-covalently binds to the ironbased stent, coupling agent and / or nano- or sub-micrometric structures to modulate the chemical, physical, and / or biological properties of the stent surface.

[0075] A “treatment” refers to both therapeutic treatment and prophylactic or preventative measures, wherein the object is to prevent or slow down (lessen) the targeted pathologic condition or disorder. Those in need of treatment include those already with the disorder as well as those prone to have the disorder or those in whom the disorder is to be prevented.

[0076] A “diazonium salt” and a “aryldiazonium salt” are used indifferently in the present invention to refer to a molecule comprising an aryl group covalently linked to a diazonium N2+group, preferably in presence of a counterion. An “aryl” group is a functional group or substituent derived from an aromatic ring, usually an aromatic hydrocarbon, such as phenyl or naphthyl.

[0077] A “microgalvanic layer" is a layer which presence on at least part of the surface of the stent triggers a microgalvanic effect leading to accelerated corrosion of the iron or iron alloy of the stent. The microgalvanic layer comprises a conductive material which standard electrode potential (SEP) is higher than that of the stent material, ie iron or the iron alloy. The SEP of iron is about -0.44V versus standard hydrogen electrode.

[0078] By “layer” is meant a coating or part of a coating which extends on at least part of the surface of the stent or of another layer. The thickness of the layer is typically lower than its other dimensions.

[0079] The “outer surface” of the stent is the surface of the stent that is (or will be) in direct contact with the body.

[0080] By “nanostructure” is meant a structure which exhibits at least one dimension comprised between 1 and 100 nm.

[0081] By “sub-micrometric structure” is meant a structure which exhibits at least one dimension comprised between 100 nm and 999 nanometers, 100 nm being excluded from the range.

[0082] The term “about” relative to a numerical value relates to an interval ranging between ±10% of the numerical value, preferably ±5% thereof, more preferably ±2% thereof, in particular ±1% thereof.

[0083] Bioresorbable stent

[0084] The bioresorbable stent according to the invention is a medical device adapted for temporary implantation within a body lumen. The body lumen may be selected from the group consisting of arteries, veins, gastrointestinal tract, biliary tract, urethra, trachea, hepatic shunts and fallopian tubes. Preferably, the body lumen is an artery, such as a coronary artery, a mesentery artery, a peripheral artery and / or a cerebral artery, more preferably a coronary artery.

[0085] In some embodiments, the bioresorbable iron-based stent is a bioresorbable endovascular or extravascular stent, preferably a bioresorbable endovascular stent.

[0086] The iron-based stent is a stent which is made of iron or an iron alloy comprising at least 50 at % iron (before coating). In some embodiments, the iron-based stent is an iron stent. In some other embodiments, the iron-based stent is an iron alloy stent. The iron alloy comprises at least 50 at % iron, preferably at least 60 at % iron, preferably at least 70 at % iron, preferably at least 80 at % iron, preferably at least 90 at % iron, more preferably at least 95 at % iron.

[0087] Typical iron alloys that may constitute the stent of the invention include Fe with at least one element selected from the group consisting of: Li, Na, P, S, K, Ca, Ti, Co, Ni, Cu, Ga, Sr, Y, Zr, Nb, Mo, Ag, Sn, I, Cs, Hf, Ba, Ge, B, O, Ta, W, Re, Os, Ir, La, Ce, Sm, Gd, Mn, C, Si, N, Zn, Mg, Pt, Pd and Au.

[0088] According to the present invention, the term “iron alloy" also encompasses iron composites, such as iron metal matrix compositions, with the addition of non-metallic compounds (<50 wt.%) to the pure Fe or the above-mentioned alloys. Examples of non-metallic compounds are: carbon nanotubes (CNT), carbides, nitrites, borides, oxides, hydroxyapatite, bioglasses, polymers, natural materials and minerals.

[0089] Examples of such iron alloys include FeMn, FeZn, FeMgZn, FeMgZn, FePt, FePd, FeAu and composites can be FeCNTs.

[0090] The bioresorbable stent according to the invention may comprise, in addition to the microgalvanic layer, any other suitable partial or total coating. Said other coating may be positioned either between the stent and the microgalvanic layer, or on the outside of the microgalvanic layer. Said other coating may for instance comprise a polymeric coating, and / or a coating suitable for delivering an active agent. In some embodiments, the presence of a polymeric coating on the microgalvanic layer allows delaying the contact between the microgalvanic layer and a body fluid, thereby delaying the occurrence of the microgalvanic effect.

[0091] The polymer of the polymeric coating is preferably a biodegradable or bioerodible polymer. Examples of biodegradable polymers include polycaprolactone (PCL), poly(lactide-co- glycolide) (PLGA), polylactide (PLA), polyglycolide (PGA), PLGA-PEG (polyethylene glycol), PLA-PEG, PLA-PEG-PLA and copolymers and mixtures thereof.

[0092] The stent may be formed from a wire of iron-based material, said wire being formed into series of waveforms, such as sinusoidal waveforms. The waveform is typically helically wound to form a stent with a tubular shape. The stent may be formed from a thin-wall tube of iron-based material by machining techniques, such as laser, electro-discharging, waterjet, electron beam, ion beam, etc. The stent may be formed from deposition techniques, such as electroplating, Physical Vapor Deposition (PVD), Chemical Vapor Deposition (CVD), etc., using iron-based material. The stent may be formed from additive manufacturing techniques, such as Laser Powder Bed Fusion (LPBF), Direct Energy Deposition (DED), Electron Beam Melting (EBM), etc., using iron-based material. The example used in the patent is based on thin- wall tube.

[0093] Another object of the present invention is an iron-based wire which is at least partially coated with a microgalvanic layer comprising nano- or sub-micrometric structures of a conductive material bonded to an organic primer layer. The wire may be formed into series of waveforms, optionally further helically wound, or not.

[0094] All features disclosed above for the iron-based stent apply similarly to the iron-based wire.

[0095] Microgalvanic layer

[0096] As detailed above, the microgalvanic layer comprises nano- or sub-micrometric structures of a conductive material which standard electrode potential (SEP) is higher than that of the stent material, ie iron or the iron alloy. In some embodiments, the SEP of the conductive material is higher that -0.44V versus standard hydrogen electrode.

[0097] The microgalvanic layer typically comprises an organic primer layer and nano- or submicrometric structures of a conductive material bound to the organic primer layer. The organic primer layer of the microgalvanic layer is bound to the stent.

[0098] The microgalvanic layer is present on at least part of the outer surface of the stent, preferably on the whole outer surface of the stent. In some embodiments, the microgalvanic layer is present on at least 50%, preferably at least 60%, preferably at least 70%, preferably at least 80%, preferably at least 90%, preferably at least 95%, more preferably at least 99%, of the outer surface of the stent. Without wishing to be bound by any theory, the Inventors believe that the iron corrosion rate may be modulated by the size of the outer surface of the stent that is coated with the microgalvanic layer. Smaller coated surface may increase iron exposure and thus accelerate corrosion.

[0099] The thickness of the microgalvanic layer is typically comprised between about 5 nanometers and about 10 micrometers, preferably between about 5 nanometers and about 1 micrometer. The thickness of the microgalvanic layer will depend among others on the nature of the coupling agent forming the organic primer layer, and of the nano- or sub-micrometric structures. The thickness of the microgalvanic layer may also be controlled to monitor the time of occurrence and the intensity of the microgalvanic effect, thus monitoring the stent bioresorption kinetics and / or time. The role of the organic primer layer is to promote stable adhesion between the metal stent and the nano- or sub-micrometric structures. The organic primer layer also allows tuning the microgalvanic corrosion process, such as the microgalvanic corrosion kinetics. Actually, by selecting suitable coupling agents and suitable nano- or sub-micrometric structures, it is possible to obtain the desired corrosion parameters, such as the desired corrosion rate. It is possible for example by selecting the suitable parameters to accelerate or slow down the corrosion as desired. In some embodiments, the organic primer layer is formed by the coupling agent, the coupling agent comprising at least two functions, one capable of binding to the ironbased stent surface, and the other capable of binding to the nano- or sub-micrometric structures. The organic primer layer is typically obtained by contacting the stent and the nano- or submicrometric structures in presence of a coupling agent.

[0100] The thickness of the organic primer layer will be dependent among others on the nature of the coupling agent and on the conditions used for forming the layer. Preferably, the thickness of the organic primer layer is selected so that it does not prevent the microgalvanic corrosion between the iron or iron alloy and the metal of the nano- or sub-micrometric structures.

[0101] The coupling agent may be any molecule suitable to bind the iron or iron alloy stent and the nano- or sub-micrometric structures.

[0102] The binding of the coupling agent and the stent may be of any type. In some embodiments, the binding is through at least one covalent bond, for instance a covalent bond obtained from reduction of an aryldiazonium salt. In some other embodiments, the binding between the coupling agent and the stent is a coordination bond obtained via the terminal functional group of the coupling agent, such as the terminal functional group of the 4-functionalized benzenediazonium salt.

[0103] The binding of the coupling agent and the nano- or sub-micrometric structures may be of any type. In some embodiments, the binding is through an electrostatic force. In some other embodiments, the binding is through at least one covalent bond, for instance a covalent bond obtained from reduction of an aryldiazonium salt.

[0104] In some embodiments, the coupling agent is selected from the group consisting of aryldiazonium salts, phosphonates, phosphates, siloxane compounds, including poly(ethylene glycol) (PEG) containing siloxanes, polyamines, such as poly dopamine (PDA), and polyimines, such as polyethylenimine (PEI). In some embodiments, the coupling agent is selected from the group consisting of aryldiazonium salts, phosphonates, phosphates and siloxane compounds, including poly(ethylene glycol) (PEG) containing siloxanes.

[0105] Preferably, the coupling agent is an aryldiazonium salt or a mixture of aryldiazonium salts.

[0106] The organic primer layer typically comprises aryl groups.

[0107] In some embodiments, the organic primer layer is an oligo- or poly-aryl layer obtained by surface grafting using aryldiazonium salts between the stent surface and the nano- or submicrometric structures. In such embodiments, the aryldiazonium salt is the coupling agent. The synthesis of aryldiazonium salts is well known in the art, for instance from the corresponding arylamines in presence of a nitrite source. In some embodiments, the aryldiazonium salt is a 4- functionalized benzenedi azonium salt. In some embodiments, the aryldiazonium salt is a calixfn] arenediazonium salt, such as a calix[4] arenediazonium salt or a calix[6] arenediazonium salt, or a mixture thereof. In some embodiments, the calixfn] arenediazonium salt comprises or consists of 4-functionalized benzenediazonium salts covalently bonded with each other, to form the calixarene structure. In some embodiments, all benzenediazonium salts forming the calixfn] arenediazonium salt are 4-functionalized. In other embodiments, only some of the benzenediazonium salts forming the calixfn] arenediazonium salt are 4-functionalized. The calixfn] arenediazonium salt may comprise 1, 2, 3, 4, 5 or 64-functionalized benzenediazonium salts. The calix[n]arenediazonium salt may comprise 0, 1, 2, 3, 4 or 5 non 4-functionalized benzenediazonium salts.

[0108] The 4-functionalized benzenediazonium salt, either alone or in the calixfn] arenedi azonium salt, is typically functionalized with a chemical group suitable for binding the nano- or submicrometric structures. In some embodiments, the 4-functionalized phenyl diazonium salt is selected from the group consisting of 4-cyanobenzenediazonium salts, 4- nitrobenzenediazonium salts, 4-aminobenzenediazonium salts, 4-ethynylbenzenediazonium salts and 4-carboxybenzenediazonium salts. In a preferred embodiment, the 4-functionalized benzenediazonium salt is a 4-cyanobenzenediazonium salt. In another embodiment, the 4- functionalized benzenediazonium salt is a 4-ethynylbenzenediazonium salt. In another embodiment, the 4-functionalized benzenediazonium salt may be 4-carboxybenzenediazonium salt, 4-(aminomethyl)benzenediazonium salt, and / or 4-boronobenzenediazonium salt. In another embodiment, the 4-functionalized benzenediazonium salt may be 4- cyanobenzenediazonium salt, 4-ethynylbenzenediazonium salt, 4-carboxybenzenediazonium salt, 4-(aminomethyl)benzenediazonium salt, and / or 4-boronobenzenediazonium salt.

[0109] The counterion of the aryldiazonium salt may be any suitable counterion. In some embodiments, the counterion is selected from the group consisting of halides, such as chloride, bromide, fluoride and iodide, preferably chloride, sulfate, hexafluorophosphate, tosylate and tetrafluoroborate. Preferably, the counterion of the aryldiazonium salt is tetrafluoroborate.

[0110] In a preferred embodiment, the aryldiazonium salt is 4-cyanobenzenediazonium tetrafluoroborate. In another embodiment, the aryldiazonium salt is 4- ethynylbenzenediazonium tetrafluoroborate (DCC). In another embodiment, the aryldiazonium salt may be 4-carboxybenzenediazonium tetrafluoroborate, 4-(aminomethyl)benzenediazonium tetrafluoroborate, and / or 4-boronobenzenediazonium tetrafluoroborate. In another embodiment, the aryldiazonium salt may be 4-cyanobenzenediazonium tetrafluoroborate, 4- ethynylbenzenediazonium tetrafluoroborate, 4-carboxybenzenediazonium tetrafluoroborate, 4- (aminomethyl)benzenediazonium tetrafluoroborate, and / or 4-boronobenzenediazonium tetrafluoroborate.

[0111] Aryldiazonium salts are advantageous in that they form a stable linkage with various surfaces, using low cost procedures. Furthermore, the use of aryldiazonium salts as coupling agent allows controlling the microgalvanic layer properties. Aryldiazonium salts may also be postfunctionalized.

[0112] One skilled in the art is able to select the suitable coupling agent(s) to bind the nano- or submicrometric structures to the stent depending among others on the nature of the stent material, the nature of the nano-or sub-micrometric structures, and the desired degradation rate by corrosion.

[0113] The nature of the coupling agent, for instance the nature of the functionalizing group of the aryldiazonium salt, may impact the electron transfer between the nano- or sub-micrometric structures and the stent. One skilled in the art may thus finely tune the organic primer layer to obtain the desired corrosion process and kinetics. A more efficient corrosion may for instance be favored when a coupling agent allowing a faster and / or more efficient electron transfer is used. Conversely, a less efficient corrosion may be favored when a coupling agent allowing a slower and / or less efficient electron transfer is used.

[0114] The nano- or sub-micrometric structures are nano- or sub-micrometric structures of a conductive material. In the context of the invention, a “conductive material” encompasses both a purely conductive material and a semiconductive material. In order for the microgalvanic effect to accelerate corrosion of the iron-based stent, the conductive material must be higher than iron or the iron alloy in the series of metals and semi-metals according to their nobility, which is known as the galvanic series or the electropotential series.

[0115] In addition, the conductive material of the nano- or sub-micrometric structures is preferably biocompatible, more preferably its biocompatibility is equal or higher than that of iron or the iron alloy.

[0116] In some embodiments, the conductive material of the nano- or sub-micrometric structures is selected from the group consisting of silver, gold, carbon and platinum. In some embodiments, the conductive material of the nano- or sub-micrometric structures may be selected from the group consisting of silver, gold, carbon, platinum, palladium and a transition metal oxide. In a particular embodiment, the conductive material of the nano- or sub-micrometric structures is different from palladium and / or from a transition metal oxide.

[0117] The presence of some nano- or sub-micrometric structures, such as gold nano- or submicrometric structures, in the micro-galvanic layer will among others reduce the release of Reactive Oxygen Species (ROS).

[0118] The shape and size of the nano- or sub-micrometric structures may vary in a wide range. In some embodiments, at least one dimension of the nanostructures or sub-micrometric structures is comprised between about 1 nm and about 999 nm. In the present invention, when a dimension of a set of nano- and / or sub-micrometric structures is mentioned, it refers to the mean value of said dimension in the set of nano- and / or sub-micrometric structures.

[0119] The size of the nano- or sub-micrometric structures may be measured by any suitable technique known in the art, such as by electron microscopy, including Transmission Electron Microscopy (TEM) or Scanning Electron Microscopy (SEM), or by Dynamic Light Scattering (DLS).

[0120] Typical shapes of nanostructures or sub-micrometric structures include particles, such as spheres, rods, stars, tubes, cages, ribbons, rings, shells, wires, quantum dots and fibers. In some embodiments, the nanostructures are nanospheres or nanotubes.

[0121] In some embodiments, the nanostructures or sub-micrometric structures are isotropic, such as spheres.

[0122] In some embodiments, the nanostructures or sub-micrometric structures are anisotropic, such as rods or stars. In some embodiments, the nanostructures or sub-micrometric structures are a mixture of isotropic and anisotropic nanostructures or sub-micrometric structures.

[0123] In some embodiments, the nano- or sub-micrometric structures coated on a stent are homogeneous in terms of conductive material, of shape and of mean dimensions. Being homogeneous in terms of mean dimension means that the distribution of the size of the nano- or sub-micrometric structures is monomodal, and preferably monomodal with a low full width at half maximum.

[0124] In some embodiments, the coated stent comprises at least two different types of nano- or submicrometric structures. In some embodiments, the coated stent comprises:

[0125] - Nano- or sub-micrometric structures of at least two different conductive materials,

[0126] - Nano- or sub-micrometric structures of at least two different shapes, and / or

[0127] - Nano- or sub-micrometric structures of at least two different sizes, which means that the size distribution is multimodal.

[0128] Particles, including nanoparticles and sub-micrometric particles, are such that any of their 3 dimensions is comprised between aboutl nm and about 999 nm. Particles may be of any shape, preferably they are spherical.

[0129] Tubes, such as nanotubes and sub-micrometric tubes, are such that two of their 3 dimensions are comprised between about 1 and about 999 nm. The other dimension of the tubes, in other words the length of the tubes, may vary in a wide range. Typically, the carbon nanotubes length is comprised between 500 nm and 5 micrometers. In some embodiments, the tubes, such as the nanotubes, are single-walled tubes. In other embodiments, the tubes, such as the nanotubes, are multi-walled tubes.

[0130] In some embodiments, the nanostructures or sub-micrometric structures are nanoscaled.

[0131] In some embodiments, the nanostructures comprise or consist of gold nanoparticles. Before binding to the organic primer layer, the gold nanoparticles may present as a colloidal suspension in a fluid medium such as water, an organic solvent or a gel. When the nanostructures comprise gold nanoparticles, the coupling agent is preferably an aryldiazonium salt, more preferably a 4- cyanobenzenediazonium salt, such as 4-cyanobenzenediazonium tetrafluoroborate or a 4- ethynylbenzenediazonium salt, such as 4-ethynylbenzenediazonium tetrafluoroborate. Even more preferably, the coupling agent is a 4-cyanobenzenediazonium salt, such as 4- cyanobenzenediazonium tetrafluoroborate. The gold nanoparticles can also be formed in situ in presence of iron from the precursor of gold salt. In some embodiments, the nano- or sub-micrometric structures are functionalized by at least one molecule (also called functionalizing molecule), so as to confer the stent advantageous properties. For instance, the nano- or sub-micrometric structures may be functionalized by a molecule, so as to further improve the biocompatibility, corrosion susceptibility and / or oxidative stability of the stent. In particular embodiment, the nano- or sub-micrometric structures are functionalized by at least one functionalizing molecule selected from the group consisting of an anti-oxidant, a prostacyclin receptor, and a drug, such as an anti-proliferative agent, an anti-thrombotic drug, a statin-based drug or an anti-inflammation drug, preferably by an anti-oxidant. The anti-oxidant may be selected from the group consisting ofN-acetylcysteine (NAC), vitamins (such as vitamin C or E), mitochondria targeted anti-oxidants (such as MitoQ), polyunsaturated fatty acids (such as omega-3 or omega-6), polyphenol (such as flavonoid), and astaxanthine. In a particular embodiment, the nano- or sub-micrometric structures are functionalized by NAC, which is an essential endogenous anti-oxidant that can advantageously prevent local ROS formation and protect human endothelial and stem cells from oxidative stress.

[0132] In some embodiments, the functionalizing molecule is a statin-based drug, such as atorvastatin or rosuvastatin, which reduces blood cholesterol levels and decreases the risk of cardiovascular diseases.

[0133] Typically, the nano- or sub-micrometric structures are functionalized by a functionalizing molecule via physisorption (usually driven by Van der Waals forces), electrostatic attraction, hydrogen bonding and / or chemical bonding (such as covalent conjugation via chemical coupling or click chemistry).

[0134] In the case where the nano- or sub-micrometric structures are functionalized by a functionalizing molecule, the coupling agent for coupling the functionalizing molecule and the nano- or sub-micrometric structures is advantageously selected as suitable for reacting with the functionalizing molecule or a precursor thereof. For instance, the coupling agent may be selected as suitable for implementing a carboxylic acid / amine reaction (for instance an EDC / NHS coupling), an alkyne / azide or alkyne / diol reaction (specifically a click reaction), a nitrile / azide reaction (specifically a click reaction) and / or a boronic acid / diol reaction.

[0135] In some embodiments: The nanostructures are selected from the group consisting of: gold nanoparticles, silver nanoparticles, platinum nanoparticles, palladium nanoparticles, transition metal oxide nanoparticles, and carbon nanostructures;

[0136] The coupling agent is selected from the group consisting of: 4-cyanobenzenediazonium tetrafluoroborate, 4-ethynylbenzenediazonium tetrafluoroborate, 4- carboxybenzenediazonium tetrafluoroborate, 4-(aminomethyl)benzenediazonium tetrafluoroborate and 4-boronobenzenediazonium tetrafluoroborate; and / or

[0137] The nanostructures are functionalized by an anti-oxidant which is preferably selected from the group consisting of: N-acetylcysteine, vitamins (such as vitamin C or E), mitochondria targeted anti-oxidants (such as MitoQ), polyunsaturated fatty acids (such as omega-3 or omega-6), polyphenol (such as flavonoid) and astaxanthine.

[0138] In some embodiments, the nanostructures comprise or consist of anti-oxidant-functionalized gold nanoparticles, preferably N-acetylcysteine-functionalized gold nanoparticles. In such embodiments, the coupling agent is preferably an aryldiazonium salt, more preferably a 4- ethynylbenzenediazonium salt, such as 4-ethynylbenzenediazonium tetrafluoroborate.

[0139] In some embodiments, the coupling agent used for coupling the nano- or sub-micrometric structures and the functionalizing molecule is identical to or different from the coupling agent used for coupling the nano- or sub-micrometric structures and the stent.

[0140] In some embodiments, the size of the gold nanoparticles may vary from sub-10 nm to 1 pm. In some preferred embodiments, the gold nanoparticles are nano-scaled.

[0141] In some embodiments, the nanostructures comprise or consist of platinum nanoparticles. Before binding to the organic primer layer, the platinum nanoparticles may present as a colloidal suspension in a fluid medium such as water. The platinum nanoparticles can also be formed in situ in presence of iron from the precursor of platinum salt. When the nanostructures comprise platinum nanoparticles, the coupling agent preferably comprises carboxylic acidic functions, for instance it may be an aryldiazonium salt substituted in position 4 with a COOH group.

[0142] In some embodiments, the nanostructures comprise or consist of carbon nanostructures, such as graphene, fullerenes and / or carbon nanotubes. When the nanostructures comprise or consist of carbon nanostructures, the coupling agent preferably comprises carboxylic acidic, cyano, amino and / or ethynyl functions, for instance it may be an aryldiazonium salt substituted in position 4 with a COOH, CN, NH2 or C=CH group. In some embodiments, the nanostructures comprise or consist of silver nanoparticles. Before binding to the organic primer layer, the silver nanoparticles may present as a colloidal suspension in a fluid medium such as water.

[0143] The Inventors have evidenced that the bioresorbable iron-based stents according to the invention present a corrosion rate that is more than about 1.5 times higher than that of the corresponding non-coated iron-based stents. Furthermore, the bioresorbable iron-based stents according to the invention have been shown to have an increased biocompatibility in comparison with the corresponding non-coated iron-based stents.

[0144] Methods for producing the coated bioresorbable stents according to the invention are within ordinary skill in the art. In some embodiments, the coated bioresorbable stents are obtained by coating a bioresorbable iron-based stent with a microgalvanic layer as defined herein. In some embodiments, the microgalvanic layer is prepared before being coated onto the iron-based stent. In some other embodiments, the microgalvanic layer is created directly on the surface of the iron-based stent.

[0145] Process for coating, a bioresorbable iron-based stent

[0146] Another object of the present invention is a process for coating a bioresorbable iron-based stent or a part thereof. Also encompassed is a process for manufacturing a bioresorbable iron-based stent according to the invention, comprising a step of coating the bioresorbable iron-based stent with a process for coating according to the invention.

[0147] The process comprises a step of contacting the bioresorbable iron or iron-alloy stent or a part thereof with nano- or sub-micrometric structures and / or a precursor thereof and with a precursor of an organic primer layer (ie a coupling agent as defined above).

[0148] The contacting may be implemented by any suitable method. Preferably, the contacting may be implemented by contacting the stent or a part thereof with an aqueous solution or suspension comprising the nano- or sub-micrometric structures and / or precursors thereof and the precursor of the organic primer layer. Preferably, the contacting is implemented by immersing the stent or a part thereof in the aqueous solution.

[0149] In some embodiments, the contacting of the stent or part thereof with the coupling agent is implemented first, and then the obtained stent is further contacted with the nano- or submicrometric structures or precursor thereof. In some preferred embodiments, the stent or part thereof is simultaneously contacted with the precursor of the organic primer layer and with the nano- or sub-micrometric structures or a precursor thereof. The precursor of the organic primer layer is typically the coupling agent as defined above.

[0150] In some embodiments, the nano- or sub-micrometric structures are formed in situ, and a precursor of the nano- or sub-micrometric structures is used.

[0151] The precursor of the nano- or sub-micrometric structures may be any suitable compound known to be suitable to form the desired nano- or sub-micrometric structures in specific conditions. For instance, the precursor of gold nanoparticles may be chloroauric acid HAuCh. The precursor of platinum nanoparticles may be chloroplatinic acid HPtC

[0152] In some embodiments, a reducing agent, such as NaBF , is present in the aqueous solution. The presence of the reducing agent is particularly useful when the coupling agent binds to the stent and / or to the nano- or sub-micrometric structures in reductive conditions. For instance, when the coupling agent is an aryldiazonium salt, such as 4-cyanobenzenediazonium tetrafluoroborate, the binding to the iron-based stent may occur though reduction of the diazonium salt.

[0153] In a specific embodiment, the nanostructures are gold nanoparticles and the coupling agent is 4-cyanobenzenediazonium tetrafluoroborate. In such embodiment, the process according to the invention may comprise contacting the iron-based stent, preferably the iron stent, or part thereof, with an aqueous solution comprising 4-cyanobenzenediazonium tetrafluoroborate and chloroauric acid.

[0154] The concentration of the coupling agent in the aqueous solution is preferably comprised between 0.05 mM and 10 mM, preferably between 0.1 mM and 5 mM, or may be in particular about 0.2 mM or about 5 mM. For instance, the concentration of the coupling agent, such as 4- cyanobenzenediazonium tetrafluoroborate, in the aqueous solution is preferably comprised between 0.05 mM and 2 mM, preferably between 0.1 mM and 0.5 mM, in particular it is about 0.2 mM.

[0155] The concentration of the nanoparticles or of the precursor thereof, such as chloroauric acid or chloroplatinic acid, in the aqueous solution is preferably comprised between 0.01 mM and 1 mM, preferably between 0.05 mM and 0.2 mM or between 0.05 mM and 0.7 mM, in particular it is about 0.1 mM or about 0.5 mM. In a particular embodiment, the concentration of the nanoparticles or of the precursor thereof, such as chloroauric acid or chloroplatinic acid, in the aqueous solution is comprised between 0.05 mM and 0.2 mM, in particular is about 0.1 mM.

[0156] The contacting may be implemented at any temperature and for any duration suitable for binding the stent or part thereof, the contacting agent and the nanostructures. In some embodiments, the duration of the contacting step is comprised between 5 minutes and 5 hours, preferably between 15 minutes and 3 hours, more preferably it is about 30 minutes or about 1 hour. In a particular embodiment, the duration of the contacting step is about 30 minutes.

[0157] In some embodiments, the contacting step is implemented at a temperature comprised between 10°C and 100°C, preferably between 20°C and 60°C, more preferably at a temperature of about 30°C.

[0158] In some embodiments, the nanostructures are functionalized by at least one molecule (also called functionalizing molecule) so as to confer the stent advantageous properties as described above. In such embodiments, the stent of the invention may be obtained by any known method in the art. In particular, in such embodiments, the stent of the invention may be obtained either by, first, coating the stent with nanostructures, as described above, and then functionalizing the nanostructures or by, first, functionalizing the nanostructures and then coating the stent with the functionalized nanostructures. Preferably, the stent of the invention is obtained by, first, coating the stent with nanostructures and then functionalizing the nanostructures.

[0159] One skilled in the art is able to select appropriate conditions for carrying out the functionalization step of the nanostructures, particularly according to the nature of the nanostructures and that of the functionalizing molecule. For instance, photochemistry conditions may be applied to functionalize the nanostructures. In such cases, a photoinitiator is typically used and the stent is typically exposed to light, especially UV light. Such photochemistry conditions enable to accelerate the functionalization step of the nanostructures and / or make this functionalization step more efficient.

[0160] Typically, the nanostructures are functionalized by a functionalizing molecule via physisorption (usually driven by Van der Waals forces), electrostatic attraction, hydrogen bonding and / or chemical bonding (such as covalent conjugation via chemical coupling or click chemistry). Advantageously, the functionalizing molecule is covalently bonded to the nanostructures.

[0161] In such embodiments, the process of the invention may further comprise a step of contacting the iron-based stent coated with the nano- or sub-micrometric structures, or part thereof, with an aqueous solution comprising the functionalizing molecule, optionally in presence of a coupling agent. The contacting step with the aqueous solution comprising the functionalizing molecule may be implemented by any suitable method. For instance, the contacting may be implemented by immersing the stent or a part thereof in said aqueous solution.

[0162] The contacting step with the aqueous solution comprising the functionalizing molecule may be implemented at any temperature and for any duration suitable for functionalizing nanostructures. For instance, the duration of said contacting step may be comprised between 5 minutes and 24 hours, preferably between 30 minutes and 20 hours, more preferably between 1 hour and 18 hours. Said contacting step may be implemented at a temperature comprised between 10°C and 100°C, preferably between 20°C and 60°C, more preferably at a temperature of about 30°C.

[0163] In a particular embodiment, the nanostructures to be functionalized are gold nanoparticles. Preferably, the nanostructures are anti-oxidant-functionalized gold nanoparticles, such as NAC- functionalized nanoparticles. The concentration of the anti-oxidant, such as NAC, in the aqueous solution may be comprised between 0.05 mM and 30 mM, preferably between 1 mM and 20 mM, even more preferably between 1 mM and 5 mM. In this particular embodiment, the coupling agent may be 4-ethynylbenzenediazonium tetrafluoroborate

[0164] In a specific embodiment, the nanostructures are NAC -functionalized gold nanoparticles, the coupling agent is 4-ethynylbenzenediazonium tetrafluoroborate, and the process according to the invention comprises: a step of contacting the iron-based stent, preferably the iron stent, or part thereof, with an aqueous solution comprising 4-ethynylbenzenediazonium tetrafluoroborate, preferably at a concentration comprised between 1 mM and 5 mM, and chloroauric acid, preferably at a concentration of about 0.5 mM; and then a step of contacting the iron-based stent, preferably the iron stent, or part thereof, with an aqueous solution comprising NAC, preferably at a concentration comprised between 1 mM and 5 mM.

[0165] The process according to the invention is a soft process and does not require harsh conditions which may alter the stent integrity and / or properties, such as its mechanical properties.

[0166] The process according to the invention allows obtaining a homogeneous coating of the stent or a part thereof with the optionally functionalized nano- or sub-micrometric structures. Preferably, the whole outer surface of the stent is coated with the optionally functionalized nano- or sub-micrometric structures. Therapeutical use

[0167] Another object of the invention is a bioresorbable iron-based stent according to the invention, for use in the treatment of an anomaly or a disease of a body lumen. The anomaly or the disease may be for instance an aneurysm, ischemic heart disease, aortic dissections, or stenosis / thrombosis affecting coronary, peripheral, or renal arteries / veins, and luminal obstructions due to either intrinsic disease or extrinsic pressure in the esophagus, colon, or bile duct. In some embodiments, the anomaly or the disease may be for instance an aneurysm or ischemic heart disease. In some embodiments, the anomaly or the disease may be for instance an aneurysm, aortic dissections, or stenosis / thrombosis affecting coronary, peripheral, or renal arteries / veins, and luminal obstructions due to either intrinsic disease or extrinsic pressure in the esophagus, colon, or bile duct. Some infections and inflammatory conditions can contribute to vascular disease or complications requiring stents. For instance, atherosclerosis-related infection which can accelerate arterial plaque buildup and increase the need of stent. Such conditions are also among the anomalies or diseases to be treated according to the invention.

[0168] In some embodiments, the bioresorbable iron-based stent according to the invention is for use in the treatment of ischemic heart disease.

[0169] In some embodiments, the bioresorbable iron-based stent according to the invention is for use in repairing a body lumen.

[0170] The invention also relates to a method for the treatment of an anomaly or a disease of a body lumen, such as an aneurysm, ischemic heart disease, aortic dissections, or stenosis / thrombosis affecting coronary, peripheral, or renal arteries / veins, and luminal obstructions due to either intrinsic disease or extrinsic pressure in the esophagus, colon, or bile duct in a patient in need thereof, comprising providing to a patient in need thereof a bioresorbable iron-based stent according to the invention. In some embodiments, the anomaly or the disease of a body lumen may be for instance an aneurysm or ischemic heart disease. In some embodiments, the anomaly or the disease of a body lumen may be for instance an aneurysm, aortic dissections, or stenosis / thrombosis affecting coronary, peripheral, or renal arteries / veins, and luminal obstructions due to either intrinsic disease or extrinsic pressure in the esophagus, colon, or bile duct.

[0171] The invention also relates to the use of a bioresorbable iron-based stent according to the invention in the treatment of an anomaly or a disease of a body lumen, such as an aneurysm, ischemic heart disease, aortic dissections, or stenosis / thrombosis affecting coronary, peripheral, or renal arteries / veins, and luminal obstructions due to either intrinsic disease or extrinsic pressure in the esophagus, colon, or bile duct. In some embodiments, the anomaly or the disease of a body lumen may be for instance an aneurysm or ischemic heart disease. In some embodiments, the anomaly or the disease of a body lumen may be for instance an aneurysm, aortic dissections, or stenosis / thrombosis affecting coronary, peripheral, or renal arteries / veins, and luminal obstructions due to either intrinsic disease or extrinsic pressure in the esophagus, colon, or bile duct.

[0172] The method according to the invention is implemented on a patient, preferably a human patient. The patient typically suffers from or is at risk of developing a cardiovascular disease, such as ischemic heart disease.

[0173] Process for increasing, the degradation and / or biocompalibililv

[0174] Another object of the invention is a process for controlling, preferably for increasing the degradation and / or the biocompatibility of a bioresorbable iron-based stent or a part thereof, comprising a step of coating the bioresorbable iron-based stent or part thereof with nano- or sub-micrometric structures bonded to an organic primer layer as defined above. In the case of gold nano- or sub-micrometric structures, the coating will reduce the release of ROS. The process according to the invention allows finely adjusting the parameters of the organic primer layer and of the nano- or sub-micrometric structures depending on the desired corrosion parameters, including the desired corrosion rate.

[0175] In the present invention, the intervals defined by the terms “comprised between (... )” should be understood as including both extremities of the intervals.

[0176] The invention will also be described in further detail in the following examples, which are not intended to limit the scope of this invention, as defined by the attached claims.

[0177] EXAMPLES

[0178] Example 1. Preliminary study on electropolished Fe discs. a) Coating of Fe discs by DCN and Au nanoparticles (Fe-Au-DCN sample)

[0179] An electropolished pure Fe disc (diameter = 12.7 mm, thickness = 0.2 mm) was immersed into a solution containing 0.5 mM of 4-cyanobenzendiazonium salts (DCN) and 1 mM of chloroauric acid (HAuCh) for 3h, followed by ultrasonication in a mixture solution of ethanol and deionized water (volume ratio = 1 : 1) for 3 min. The obtained disc with surface coating was dried under air and imaged using a scanning electron microscope (SEM). As shown in Figure 1, the Au nanoparticles (bright dots) can be observed on Fe substrate, indicating successful coating by nanoparticles. b) Characterization of the coated surface by Raman spectroscopy

[0180] The presence of polyaryl derived from DCN on surface modified Fe was confirmed by Raman spectroscopy. The presence of Au NPs, known for their excellent Raman signal enhancement capacity due to localized surface plasmon resonance, provided strong surface-enhanced Raman scattering (SERS) signals, as demonstrated in Raman spectrum (Figure 2) showing peaks corresponding to -CN group in the region of 2100-2300 cm'1. The formed polyaryl exhibited peaks in the region of 1000-1700 cm'1. And the surface oxidation should be responsible for the peak at 569 cm'1. c) Surface characterization by infrared (IR) spectroscopy.

[0181] The IR spectrum for Fe-Au-DCN was compared with a reference sample of benzonitrile. In Figure 3, a peak at 2350 cm'1indicated CO2. The peaks at 2250 cm'1and 1600 cm'1, respectively assigned to -C=N and aryl (-CeHs), could be observed for both Fe-Au-DCN and reference samples, showing the grafting of aryl bearing -CN groups on Fe surface. d) Surface characterization by X-ray photoelectron spectroscopy (XPS)

[0182] The survey spectrum of Fe-Au-DCN sample (Figure 4), with comparison of that of Fe, revealed an increase in the C and N contents while the Fe and O contents decreased, compared to the pristine Fe surface, in agreement with the formation of polyaryl layers derived from DCN on top of Fe. Interestingly, a new peak appeared, assigned to the presence of Au, confirming the deposition of Au NPs. A large amount of O (33.4 at%) was detected indicating that the sample surface was oxidized. A small amount of Cl (0.5 at%) could be also observed, likely resulting from the adsorption of Cl- ions from chloroauric acid during the sample preparation process. e) Fe corrosion studying by static immersion tests

[0183] The corrosion rate of the Fe-Au-DCN sample was assessed through an immersion test in body- simulated fluid (Hank’s solution). The sample masses were measured after 3, 7, 14 and 28 days of immersion and compared to the original mass prior to immersion. The corrosion rate was represented by the mass loss at different time points. As illustrated in Figure 5, the mass loss for both the reference Fe and Fe-Au-DCN samples increased with immersion time, with the mass loss for Fe-Au-DCN being greater than that for pure Fe. This observation indicates that the corrosion rate of the modified Fe was accelerated compared to that of the pure Fe.

[0184] These results demonstrate that the Au NPs and DCN containing surface coating can kinetically accelerate Fe corrosion. f) Evaluation of biosafety of the extracts after 3 day’s immersion testes.

[0185] Figure 6 shows the cell viability assessments conducted on mouse embryonic fibroblasts 3T3 and primary human umbilical vein endothelial cells (HUVEC) cells after cultured for 24 hours within the extracts of 3 days’ immersion solution at concentrations of 12.5%, 25% and 50% (200 pL culture media). For 3T3 cells (Figure 6a-c), all samples manifested cell viability surpassing the 70% threshold across the range of extract concentrations of 12.5%, 25% and 50%. Comparable results emerged from the assessment involving HUVEC cells (Figure 6d-f). These findings proved the robust cell viability exhibited by both 3T3 and HUVEC cells when cultivated within the extracts derived from both reference Fe and Fe-Au-DCN. This substantiates the biocompatibility of the extract samples and the compatibility with the cellular environment.

[0186] Example 2: Preparation of a first bioresorbable stent according to the invention

[0187] A 24 mm-long iron stent was prepared by laser cutting of Fe tube and treatment by electropolishing, followed by immersion in an aqueous solution comprising 4- cyanobenzenediazonium tetrafluoroborate (0.2 mM) and HAuCk (0.1 mM) for 30 minutes at 30°C.

[0188] An iron stent with a homogeneous distribution of gold nanoparticles embedded within a covalently attached polyaryl coating across its entire surface was obtained.

[0189] Figure 7 presents SEM pictures of the obtained stent.

[0190] Example 3. Study of the corrosion rate

[0191] The coated iron stent obtained in Example 2 and a similar non-coated stent were submitted to static immersion in body simulated solution (Hank’s solution) for 3 days. The iron ion concentration in the solution was studied during the 3 days to assess the efficiency of corrosion. Figure 8 presents the compared corrosion rate of both stents in terms of mass loss per day. The corrosion rate of the coated stent according to the invention is more than 1.5 times higher than that of the corresponding non-coated stent.

[0192] Example 4. Cell culture on stents surface

[0193] The biocompatibility of coated and non-coated stents was studied by seeding cells directly on stent surfaces for a duration of 72 hours. After the culture and fixation with 4% paraformaldehyde (PF A), the nuclei of human vascular endothelial cells were stained using 4',6-diamidino-2-phenylindole, while actin filaments were stained using phalloidin. After 72h incubation, very few cells were present on the uncoated Fe stent surface, as indicated by the absence of fluorescence signals for both actin and nuclei. In contrast, cells showed healthy growth and morphology on the surface-coated stent, as evidenced by the detection of fluorescence signals for both actin and nuclei.

[0194] Figure 9 presents the direct cell culture results on stent surfaces.

[0195] Example 5: In vivo and ex vivo analyses with a second bioresorbable stent according to the invention a) Preparation of a second stent according to the invention

[0196] The second stent according to the invention was prepared as described in Example 2 above, except that the temperature at which the electropolished Fe tube was immersed in the aqueous solution of DCN and HAuCk was set at 20°C. b) Animal care

[0197] Male and female White New Zealand rabbits (3.0 - 4.0 kg) were used. All animals care and experimental procedures were conducted in accordance with the 2013 French legislation, European Community guidelines (directive 2010 / 63 / UE for the Care and Use of Laboratory Animals) and the ARRIVE 2.0 guidelines. The study received approval from the regional Ethical and Animal Care Committee and French Ministry of Higher Education and Research.

[0198] For each procedure, general anesthesia was given using intra-muscular injection (IM) of ketamine (17 mg / kg), xylazine (4 mg / kg) and acepromazine (0.85 mg / kg). Local anesthesia was administered by subcutaneous (SC) injection of lidocaine (6 mg / kg). Post-operative follow-up consisted of daily observation with systematic pain evaluation and analgesia with buprenorphine administration (0.02-0.04 mg / kg / 8-hour SC), if required. c) Stents implantation

[0199] Two groups were studied:

[0200] • Group 1 (Control + AuNP-coated stent, 4 rabbits): One balloon-expandable control stent (Cordis Blue®, 5 x 18 mm, non-bioresorbable CoCr scaffold) was placed immediately below the renal ostia, followed 1-2 cm distally by a functionalized Fe-AuNPs stent deployed using a 5 * 40 mm iVascular Oceanus® balloon.

[0201] • Group 2 (Sham angioplasty + bare Fe stent, 5 rabbits): Sham angioplasty of the abdominal aorta was performed with a 5 / 40 mm Oceanus® balloon, followed by deployment of a bare Fe stent at the same location.

[0202] Stents implantation procedures were performed through a 5-French femoral sheath using a 5- French 45° diagnostic catheter and aHeadway 21 (Microvention) to deploy the devices. Aspirin (40 mg orally) was administered one day before stents implantation and continued daily until euthanasia at day 90. d) In-vivo analysis: angiographic and optical coherence tomography imaging

[0203] Experiments

[0204] Following stents implantation, digital subtraction angiography (DSA) and DynaCT were acquired to evaluate device placement (Icono, Siemens, Erlangen, Germany) through a carotid approach.

[0205] DSA and optical coherence tomography (OCT) (Dragonfly Catheter, St. Jude Medical, Westford, MA, USA) were performed on day 30 and day 90. OCT procedures were performed through right carotid 6-French sheath access and 6-French catheter. The protocol included different optional intermediate time points for OCT.

[0206] OCT imaging was acquired with a lOmm / s pull-back speed, generating 540 frames / pull-back with simultaneous intra-arterial iodine contrast injection at a rate of 3-6mL / s for a total volume of 16-24mL. The entire stent lengths were imaged. OCT image analysis was performed with Ilumien Optis post-processing software (Abbott, Lake County, IL, USA), 15 cross-sectional images at regular interval per pull-back (five proximal to the neck, five at the neck and five distal to the neck) were analyzed. All measures were performed from leading edge to leading edge. Results

[0207] All devices were successfully implanted. Post-implantation DynaCT confirmed complete arterial wall apposition in all cases. All 9 subjects had OCT at day 1, day 30 and day 90, resulting in 195 cross-sectional OCT images analyzed at each point.

[0208] • Stents expansion and lumen areas

[0209] At day 0 immediately after stent implantation using OCT, the stent expansion ratio was assessed. The stent expansion is defined as the ratio between stent lumen area (identified by circumferential area limited by the contours of the struts) and vessel lumen area (defined as contours of the vessel lumen).

[0210] The stent expansion ratio was 94.9 ± 0.3% for Fe stents, and 93.6 ± 0.2% for Fe-AuNPs stents (p < 0.001). Thus, post hoc analysis showed that Fe-AuNPs stents expansion ratio was slightly lower than that of Fe-stents.

[0211] At day 1, mean infrarenal aortic lumen area was comparable across groups: 16.26 ± 0.19 mm2for Fe stents, and 16.14 ± 0.20 mm2for Fe-AuNPs stents (p > 0.05). At day 30, the lumen area decreased significantly to 12.78 ± 0.67 mm2for Fe stents, and 12.81 ± 0.47 mm2for Fe-AuNPs stents (p < 0.001). At day 90, the lumen area remained stable: 11.82 ± 0.15 mm2for Fe-stents, and 11.95 ± 0.19 mm2for Fe-AuNPs stents (p > 0.05).

[0212] Stents lengths did not significantly change between day 0 and day 90.

[0213] • Coverage ratios

[0214] At day 30 and day 90, to assess stent-coverage with neo-intimal formation a 4-point grading scale was used to classify each strut:

[0215] - type 1: bare / uncovered strut,

[0216] - type 2: protruding / uncovered strut,

[0217] - type 3: protruding embedded / covered strut, and

[0218] - type 4: smooth embedded / covered strut.

[0219] The stent-coverage ratio was used as the number of struts covered (type 3 and 4) by neointima / total number of struts. Stent-excellent coverage ratio was also used as the number of stent struts covered and embedded in a smooth neointima (type 4) / total number of struts. Stentcoverage ratio represents the speed of endothelialization and tissue growth over the stent struts, while stent-excellent coverage represents complete arterial healing. At day 30, coverage ratios were 0.98 ± 0.02 for Fe stents, and 0.99 ± 0.02 for Fe-AuNPs stents (p < 0.001). Excellent coverage ratios were 0.86 ± 0.02 for Fe stents, and 0.90 ± 0.03 for Fe- AuNPs stents (p < 0.001).

[0220] At day 90, coverage ratios improved in all groups, reaching 1.00 ± 0.002, and 1.00 ± 0.03 for Fe and Fe-AuNPs stents respectively (p < 0.001). Excellent coverage ratios were 0.89 ± 0.19 for Fe stents, and 0.94 ± 0.12 for Fe-AuNPs stents (p < 0.001).

[0221] These results demonstrate rapid endothelialization of both Fe-stents and Fe-AuNPs-stents. Thus, gold nanoparticles do not affect the endothelialization speed compared to Fe-stents.

[0222] • Neo-intimal measures

[0223] The neo-intimal growth was determined using several endpoints. The endoluminal surface was automatically detected by the imaging systems, and manually corrected for each slice when necessary. Stent struts were manually traced and positioned in the center of the stent strut which showed a bright ‘blooming’ appearance.

[0224] Neointimal areas (corresponding to stent area - lumen area) at day 30 were 1.13±0.35 mm2for Fe-stents and 1.37±0.42 mm2for Fe-AuNPs stents (p < 0.01). At day 90, neointimal areas were 1.00±0.43mm2for Fe-stents and 1.4±0.44mm2for Fe-AuNPs stents (p < 0.01).

[0225] At day 30, neointimal ratios (corresponding to (mean stent area - mean lumen area) / mean stent area) were significantly different between Fe and Fe-AuNPs stents (0.08±0.08 vs. 0.10±0.10 respectively; p <0.001). Fe-AuNPs neointimal ratio was significantly higher than Fe-neointimal ratio (0.10±0.03 vs. 0.08±0.02; p = 0.003).

[0226] At day 90, neointimal ratios were also significantly different between Fe and Fe-AuNPs stents (0.08±0.004 vs. 0.11±0.005 respectively; p <0.001). Fe-AuNPs neointimal ratio was significantly higher than Fe-neointimal ratio.

[0227] Neointimal ratio of Fe-AuNPs increased between day 30 and day 90 (0.10±0.03 vs. 0.11±0.03; p = 0.04) contrary to Fe stents (0.08±0.02 vs. 0.08 ±0.03).

[0228] These results show that golds nanoparticles make it possible to increase the volume of neointimal formation compared to a pure Fe-stent. Qualitative analysis

[0229] At day 30 and day 90, the OCT arterial wall and lumen analysis showed for both Fe and Fe- AuNPs stents no atherosclerotic lesions, no thrombus, no calcified nodule, no spotty calcification and no macrophage accumulation. e) Ex-vivo analyses

[0230] - Sample preparation

[0231] Immediately after the 90-day imaging procedure, all the animals were euthanized followed by retroperitoneal exposure of the aorta for harvesting. The stented aorta segments were dissected and immediately fixed in 10% formalin solution for at least 24 hours. Each sample was sectioned to reveal the arterial cross-section using a disk-cutting machine equipped with a diamond cutting disk.

[0232] After cutting, each block was divided into two parts, both exposing cross-sectional surfaces at the same location. One half, containing stents with a single exposed cross-section, was sent for immunohistological staining and imaging. The remaining half was further trimmed to a thickness of 5 mm for SEM-EDX and Raman characterization. The 5 -mm blocks underwent mechanical surface polishing using diamond disks with progressively finer particle sizes (15pm, 6pm, and 3pm) to remove cutting artifacts, followed by ethanol cleaning for 1 min. To minimize electron charging effects in the polymer block, 10 nm-thick silver coating was applied by deposition.

[0233] - Histopathology analysis

[0234] Samples were dehydrated in graded ethanol baths (70%, 80%, 90%, and 100%; 24 h each, three repetitions) and subsequently embedded in cold resin. Embedding was performed in two steps:

[0235] (i) impregnation for 3 days in a solution containing 6mL of methyl methacrylate, 3.5mL of butyl methacrylate, 500pL of methyl benzoate, and 120pL of polyethylene glycol, followed by

[0236] (ii) polymerization in the same solution supplemented with 80mg benzoyl peroxide and 60pL N, N-dimethyl-p-toluidine. All samples were degassed under nitrogen (N2) and stored at -20 °C for 48 h prior to sectioning.

[0237] Resin blocks were sectioned using a tungsten knife microtome (HM 355 S, Microm) to obtain 15-pm cross-sections. Sections were mounted on Superfrost Plus Gold adhesion microscope slides pre-wetted with ethanol, dried on a slide warmer at ~37 °C, and incubated overnight at 50 °C before staining. Prior to staining, resin was removed by sequential incubation in 2-methoxyethyl acetate (2 x 20 min), 70% ethanol (10 min), 40% ethanol (10 min), and distilled water (5 min).

[0238] Hematoxylin and Eosin (H&E): Sections were washed in water, nuclei stained in hemalum (5min), rinsed, differentiated in acid alcohol, blued in lithium carbonate, and counterstained with erythrosine (3min). After dehydration in graded alcohols and xylene, slides were mounted.

[0239] Masson ’s Trichrome (MTC): Sections were stained in hemalum (15 min), differentiated, blued, and rinsed in 1% acetic acid. Cytoplasm was stained with fuchsin-culvert solution (5min), followed by 1% phosphomolybdic acid (7min, 37 °C), and light green (3min). Slides were dehydrated and mounted.

[0240] Peris DAE (iron detection): Sections were incubated with a freshly prepared 1:1 solution of potassium ferrocyanide (100 mg / 5 mL) and 2% HC1 for 20 min, rinsed, and treated with DAB solution (0.5%) for 5 min. After a water rinse, slides were incubated in 30% H2O2 (1 mL in 3mL of water, 15 min), then dehydrated and mounted.

[0241] Alizarin Red (calcium detection). Sections were rinsed in water and stained with Alizarin Red S (2 g / 100 mL water, 5 min). After removal of excess dye, sections were dehydrated in acetone (2 x 10-20 s), acetone / xylene (1:1, 10-20 s), and xylene (5 min), then mounted.

[0242] Image analysis: Stained slides were first examined under a light microscope and then digitized using aNanoZoomer 2.0-Res digital slide scanner (Hamamatsu) with NDP.Scan 3.2 software. Images were visualized with NDP.View, and quantitative analyses were performed using QuPath. Corroded areas were identified by applying a pixel classifier.

[0243] • Results

[0244] Histological cross-sections stained with Hematoxylin & Eosin, Masson’s Tri chrome, Perls- DAB, and Alizarin Red revealed well-preserved vascular architecture and confirmed the presence of neointimal tissue overlying the stent struts in all groups.

[0245] Iron deposits were visualized by Perls-DAB in Fe and Fe-AuNPs stents, consistent with ongoing biodegradation. Alizarin Red staining revealed calcium deposits for both Fe-AuNPs sample and bare Fe, but no organized thrombus was observed, without evidence of massive inflammatory infiltrates.

[0246] Quantitative histomorphometry (n = 35 sections per group; mean ± SEM) showed no between- group difference in lumen area (Fe: 13.59 ± 0.24 mm2; Fe-AuNPs: 13.93 ± 0.28 mm2; ANOVA p>0.05; Tukey-Kramer: all groups share the same letter). By contrast, neointimal area differed across groups (Fe: 1.88 ± 0.10 mm2; Fe-AuNPs: 2.06 ± 0.15 mm2; ANOVA p<0.05).

[0247] Analysis of iron-positive deposits by Perls-DAB revealed a clear distinction between bare Fe and AuNP-modified Fe stents. The percentage of surface occupied by corrosion products was significantly higher in Fe-AuNPs (21.8 ± 1.7 %) than in Fe stents (12.3 ± 1.1 %), (p < 0.01), indicating that surface functionalization by AuNP functionalization accelerated corrosion and led to more abundant iron release into the surrounding tissue.

[0248] - SEM analysis

[0249] SEM imaging was performed using a Zeiss Supra 35 scanning electron microscope (SEM) equipped with a Bruker Energy Dispersive X-ray Spectroscopy (EDX) detector. The SEM operated under standard EDX conditions at an accelerating voltage of 15 kV and a working distance of 10.5 mm. Zones of interest (ZOIs) at 100x-200x magnification were selected, focusing on the stent struts and adjacent surfaces to examine morphology (in backscattered electron (BSE) mode for atomic number Z-contrast) and to assess elemental distribution via EDX mapping. The EDX mapping acquisition time was set to 300 s for all measurements to ensure sufficient counts under identical imaging conditions.

[0250] To quantitatively analyze Fe corrosion products, all EDX images were processed using ImageJ software. The Fe elemental map was overlaid with the O map, and the pixels in the overlapped Fe / O regions were counted to identify the Fe corrosion products. The Fe strut region was defined as the areas containing Fe only, with no O overlap. The ratio of corrosion product pixels to total (corrosion product with strut) pixels was then calculated. For Ca and P analysis, the respective Ca and P elemental maps were used. Pixel counts were obtained for each element and normalized by the number of pixels of total Ca or P plus strut.

[0251] • Results

[0252] SEM-EDX mapping was employed to analyze the elemental distributions: the degradation products exhibited clear signals of Fe, O, Ca, and P.

[0253] In the Fe-specific maps, both the metallic struts and their corrosion products show strong Fe intensities. Regions exhibiting concurrent enhancement in Fe and O intensities can be attributed to Fe oxides. In both Fe- and Fe-AuNPs-stents, Ca and P intensities were also localized in areas overlapping with Fe-containing degradation products. To compare degradation behavior between bare Fe and Fe-AuNPs stents, the relative area of degradation products was quantified by calculating the pixel-based ratio:

[0254] Pixel ratio (%) = X pixels (X pixels + strut pixels) x 100%

[0255] (X = corrosion product, Ca and P)

[0256] For each sample type, 30-40 strut profiles were analyzed to determine the pixel ratios. The Fe- AuNPs samples exhibited significantly higher ratios for degradation products as well as for Ca and P, indicating a greater extent of degradation-product formation after three months of implantation. This suggests a faster Fe release in the Fe-AuNPs stents compared to a bare Festent.

[0257] - Raman characterization

[0258] Raman imaging was carried out on Horiba Xplora Plus Raman microscope, using a 785 nm laser and a lOx objective lens at 20 mW. It was recorded with lateral resolution (steps x = 28 pm and y = 23 pm) with acquisition time of Is and 2 accumulations.

[0259] • Results

[0260] Raman imaging of Fe-AuNP stent revealed four distinct regions. The average spectra showed no Raman peaks in the first region, corresponding to the pure Fe strut, which is known to be Raman-inactive. The second region was detected in the lumen, which was filled with resin; its spectrum displayed the typical Raman fingerprint of epoxy. The third region showed spectra almost same to that of the reference resin. Finally, the fourth region exhibited three characteristic peaks at 220, 290, and 402 cm'1, which can be attributed to Fe corrosion products, specifically hematite (Fe20s).

[0261] After overlaying the Raman and optical images, it was observed that the corrosion products were localized around the strut, indicating degradation of Fe after 3 months of implantation in animal models.

[0262] Example 6. Study of electropolished Fe discs coated with DCC and NAC-functionalized gold nanoparticles (Fe-Au-DCC-NAC sample) a) Sample preparation

[0263] Three electropolished pure Fe discs (diameter = 3.1 mm) were each placed in an Eppendorf tube containing a mixture of 5pL of HAuCL (0,5 M) and ImL of DCC (4- ethynylbenzenediazonium tetrafluoroborate) at the desired concentration (1 mM, 2 mM, or 5 mM).

[0264] The tubes were incubated at room temperature for 1 hour, allowing diazonium adsorption onto the metal surface, resulting in samples denoted: Fe-Au-DCC-lmM, Fe-Au-DCC-2mM, and Fe- Au-DCC-5mM.

[0265] Following incubation, the discs were washed in a 1 : 1 ethanol / water solution using an ultrasonic bath for 1 minute, to remove any iron oxides or surface residues.

[0266] Each disc was then treated with 314 pL of a solution comprising the anti-oxidant NAC (N- acetylcysteine) and with 314 pL of a solution comprising a photo-initiator (2-hydroxy-4’-(2- hydroxyethoxy)-2-methylpropiophenone; denoted PI) in different concentration, according to the following conditions:

[0267] . Fe-Au-DCC-lmM + NAC 1 mM + PI 1 mM

[0268] . Fe-Au-DCC-2mM + NAC 2 mM + PI 2 mM

[0269] . Fe-Au-DCC-5mM + NAC 5 mM + PI 5 mM

[0270] Solutions were degassed for 15 minutes with argon using a balloon system to eliminate oxygen, which may interfere with the photoreaction.

[0271] Next, the discs were exposed to UV light, ensuring the electrode surface faced upward. The exposure time was either 30 minutes (for Fe-Au-DCC-lmM) or 1 hour (for Fe-Au-DCC-2mM and Fe-Au-DCC-5mM) depending on the reagent combination, resulting in samples denoted: Fe-Au-DCC-NAC-PI-lmM, Fe-Au-DCC-NAC-PI-2mM, and Fe-Au-DCC-NAC -PI-5mM.

[0272] Discs coated with NAC-functionalized Au nanoparticles were also prepared as explained above but without any photo-initiator and without UV exposure. These samples, denoted Fe-Au-DCC- NAC-5mM, Fe-Au-DCC-5mM-NAC-10mM and Fe-Au-DCC-5mM-NAC-20mM, were used in order to verify whether the grafting reaction could also take place without exploiting photo click chemistry. b) Surface characterization by Surface-Enhanced Raman spectroscopy (SERS)

[0273] The functionalized discs Fe-Au-DCC-lmM, Fe-Au-DCC-2mM, Fe-Au-DCC-5mM, Fe-Au- DCC-NAC-PI-lmM, Fe-Au-DCC-NAC-PI-2mM and Fe-Au-DCC-NAC-PI-5mM obtained above were placed on a standard sample slide compatible with a Raman microscope. The slide was then placed inside the sample compartment of a XploRA PLUS microscope (Horiba Scientific). The obtained SERS spectra are shown in Figure 10. It results from this figure that: comparing the spectra of samples comprising DCC-NAC-PI with those comprising DCC alone, an increase is observed in the peak at 2100 cm1(-C=C-) and a decrease is observed in the peak at 2000 cm1(Au-CCH). These variations indicate that grafting has taken place, as they reflect a change in the conformation of the DCC linked to the surface;

[0274] - in samples with NAC-PI, a marked increase in the peak to about 360 cm1is also observed, indicating the formation of a Au-S bond. This variation also confirms the functionalization process and the formation of the bond between the surface and the NAC anti-oxidant; and among the samples containing DCC and NAC-PI, Fe-Au-DCC-NAC-PI-5mM showed the greatest decrease in the peak at 2000 cm1and the most significant increase in the peak at 360cm A Based on these results, the DCC concentration chosen for subsequent experiments was 5mM.

[0275] In addition, after acquiring single-point spectra, SERS mapping was performed over selected areas, which allowed to verify the functionalization at different points on the surface. The corresponding maps obtained for the sample Fe-Au-DCC-5mM and Fe-Au-DCC-NAC-PI- 5mM clearly showed a homogeneous grafting across the entire surface.

[0276] Having identified the DCC concentration of 5 mM as optimal, the trend over time of a newly Fe-Au-DCC-5mM sample (prepared as described above) was evaluated to verify the stability of the grafting over time. For this purpose, the newly prepared sample was analysed using SERS and then subjected to new measurements immediately after the preparation and after 2, 4 and 7 days of storage at room temperature. The obtained SERS spectra are shown in Figure 11. From the superposition of the obtained spectra obtained, no significant variations emerge either in terms of position or intensity of the characteristic peaks. This result indicates that the grafting remains stable over time, confirming the robustness of the functionalization obtained. Finally, the discs functionalized with NAC but in the absence of a photo initiator and without UV exposure (Fe-Au-DCC-NAC-5mM, Fe-Au-DCC-5mM-NAC-10mM and Fe-Au-DCC- 5mM-NAC-20mM) were monitored after 1 hour, 5 hours and 18 hours from preparation. The obtained SERS spectra are shown in Figures 12 to 14. Data analysis showed consistent behaviour for all three samples. In the case of the Fe-Au-DCC-NAC-5mM sample (Figure 12), a progressive decrease in the peak at 2000 cm1was observed over time, characteristic of the - C=CH terminal group, as described above, accompanied by an increase in the signal to about 360 cm '. indicating the formation of a Au-S bond due to NAC attack. The same trend was also found in the Fe-Au-DCC-5mM-NAC-10mM sample (Figure 13), where the variation of peaks appears more marked already after 5 hours, suggesting a greater reaction speed in the presence of a higher concentration of NAC. Finally, in the Fe-Au-DCC-5mM-NAC-20mM sample (Figure 14), the peak intensity at 2000 cm decreases even more rapidly, while the contribution at 360 cm1becomes predominant after just a few hours, confirming an even higher grafting efficiency as the NAC concentration increases. These results demonstrate an effective coating of the stent with NAC -functionalized gold nanoparticles, with different concentration of NAC. Moreover, Raman mapping confirmed that the grafting was uniformly distributed across the entire surface for all the three samples. c) Surface characterization by X-ray photoelectron spectroscopy (XPS)

[0277] To confirm the surface composition of the samples and assess the chemical status of sulphur after functionalization, an XPS analysis was performed. The XPS analysis was performed using an XPS spectrometer equipped with a monochromatic Al Ka X-ray source (hv = 1486.6 eV). Spectra were acquired under ultra-high vacuum (UHV) conditions, with a scan area of approximately 400 pm and energy steps suitable for high-resolution analysis. After the acquisition of XPS spectra, the energy scale was calibrated using the Cis carbon peak at 284.8 eV to correct for any instrumental shifts.

[0278] The samples analysed were: Fe-Au-DCC-5mM, Fe-Au-DCC-NAC-PI-5mM, Fe-Au-DCC- NAC-5mM after 18 hours of incubation and Fe-Au-DCC-5mM-NAC-20mM after 18 hours of incubation.

[0279] The following table shows the atomic percentages of the elements detected for each sample:

[0280] No sulphur was detected in the Fe-Au-DCC-5mM sample, while in the NAC functionalized samples, an increase in the S2p signal was observed, confirming the surface modification.

[0281] The obtained XPS S2p spectrum of the Fe-Au-DCC-NAC-PI-5mM, Fe-Au-DCC-NAC-5mM and Fe-Au-DCC-5mM-NAC-20mM samples are shown in Figures 15 to 17 respectively. It results from these figures that these samples showed that the C-S binding component is significantly greater than the Au-S bonding component, indicating that NAC functionalization has indeed occurred. A clear reduction of the Au-S component in favor of the C-S component was observed, which is consistent with the formation of bonds between NAC and the surface even in the absence of UV photoinitiation. d) ORAC

[0282] The Oxygen Radical Absorbance Capacity (ORAC) assay was used to assess the anti-oxidant activity of the functionalized iron discs. The measurements were carried out using a Varioskan™ LUX multimode microplate reader, made by Thermo Scientific.

[0283] Each disc was placed in a well of a black 96-well plate. 150 pL of fluorescein solution and 50 pL of PBS were added to each well containing a disc. Control and experimental conditions included untreated Fe discs, gold-treated discs, and samples functionalized with different NAC concentrations, both with and without UV -induced photoactivation.

[0284] The tested discs were:

[0285] • Pure Fe disc

[0286] . Fe-Au-DCC-5mM

[0287] • Fe-Au-DCC-NAC-5mM (without UV-induced photoactivation)

[0288] • Fe-Au-DCC-5mM-NAC-20mM (without UV-induced photoactivation) Fe-Au-DCC-NAC-PI-5mM (UV photoactivated)

[0289] Immediately before measurement, 25 pL of AAPH (2,2' azobis(2 amidinopropane) dihydrochloride) was rapidly added to each well, and the plate was inserted into the Varioskan™ LUX reader set at 37 °C. Fluorescence readings were taken every minute for 60 minutes (excitation 485 nm, emission 520 nm). The anti-oxidant activity was evaluated by calculating the area under the fluorescence decay curve (AUC) and comparing it to the Trolox standard curve.

[0290] Figure 18 represents the normalized fluorescence intensity of each sample over time. It results from this figure that, for the three samples comprising the anti-oxidant NAC, the fluorescence intensity decreases to a lesser extent than that of the other samples which do not comprise any anti-oxidant. This confirms that NAC exhibits anti-oxidant activity even when functionalized onto gold nanoparticles. e) Cells tests

[0291] To assess the biocompatibility and the type of cell-material interaction of the developed samples, a series of in vitro tests were performed using HUVEC cells.

[0292] The cells, stored at -80 °C, were thawed in a 37 °C water bath until fully defrosted. After thawing, the cell suspension was transferred into a 15 mL Falcon tube, and 3 mL of a previously prepared dimethylsulfoxide (DMSO) culture medium was added. The tube was then centrifuged for 5 minutes at 900 rpm. Following centrifugation, the supernatant was carefully removed to eliminate DMSO. The cells were visible as a pellet at the bottom of the tube, adhered to the surface.

[0293] After removing the supernatant, 1 mL of DMSO culture medium was added, and the cells were gently mixed to resuspend them. Subsequently, 15 mL of DMSO culture medium and 0.5 mL of the cell suspension were added into a 75 cm2flask. The flask was then placed in an incubator at 37 °C with controlled CO2, and the cells were allowed to grow for 24 hours. For a negative control group, 500 pL of fresh culture medium was added.

[0294] After the culturing phase, HUVEC cells were used in three biological assays to evaluate their interaction with the different materials. Specifically, the tests aimed to assess (i) the possible cytotoxic effects based on cell morphology, (ii) the impact of any substances released from the functionalized material and (iii) the response of cells in direct contact with the surface. (i) Cell morphology

[0295] The aim of this first experiment was to evaluate cell morphology, as it serves as a key indicator of cellular viability, physiological state, and compatibility with biomaterials.

[0296] A cell counting phase was performed to prepare the correct cell seeding concentration. The goal was to achieve a final concentration of 50,000 cells / mL, which corresponds to 25,000 cells per well, based on a volume of 500 pL per well.

[0297] The following discs were placed with the functionalized side facing downward to ensure direct contact with the cells:

[0298] • Negative control

[0299] • Pure Fe disc (control)

[0300] . Fe-Au-DCC-5mM

[0301] • Fe-Au-DCC-NAC-5mM (without UV-induced photoactivation)

[0302] • Fe-Au-DCC-5mM-NAC-20mM (without UV-induced photoactivation)

[0303] • Fe-Au-DCC-NAC-PI-5mM (UV photoactivated).

[0304] After 24 hours of incubation the discs were extracted. Subsequently, 500 pL of 4% paraformaldehyde (PFA) solution were added to each well and the slide was incubated for 30 minutes at 4 °C in the refrigerator. After fixation, the PFA solution was discarded and replaced with 500 pL of 0.1% Triton X-100, followed by 5 minutes of incubation at room temperature.

[0305] Once permeabilization was completed, the solution was removed and 500 pL of Rhodamine- Phalloidin solution (0.165 pM) were added to each well and incubated for 60 minutes at room temperature. To complete the staining, 0.5 pL of DAPI (300 pM stock solution, final concentration 300 nM) was added to each well and incubated for 5 minutes at room temperature.

[0306] Following the staining procedures, the residual solutions were carefully removed and the side walls of the Lab-Tek chamber were detached. A drop of mounting medium was then applied onto the slide, and a coverslip was placed on top to preserve the sample. The samples were finally observed using a ZEISS confocal fluorescence microscope. The obtained images are shown in Figure 19(a)-(f).

[0307] (ii) Release control

[0308] A release control test was performed to evaluate the effect of possible compounds released from the material surface into the culture medium. This approach allows the assessment of the material’s indirect impact on cell viability and morphology, without direct contact between the cells and the sample.

[0309] To this end, Eppendorf tubes were prepared with ImL of complete culture medium and one of the following samples:

[0310] • Negative control

[0311] • Fe disc (control)

[0312] • Fe-Au-DCC-5mM-NAC-20mM (without UV -induced photoactivation)

[0313] • Fe-Au-DCC-NAC-PI-5mM (UV photoactivated).

[0314] After three days of incubation at 37 °C in a CCL-controlled environment, the culture medium containing the material samples was collected from the Eppendorf tubes and transferred into Lab-Tek chamber slides.

[0315] The cell concentration in this experiment was 50,000 cells per well, corresponding to a seeding density of 100,000 cells / mL, considering a volume of 500 pL per well.

[0316] The Lab-Tek slides were then incubated for 24 hours under the same conditions, and the subsequent steps were carried out following the protocol described in point (i) above.

[0317] The obtained ZEISS confocal fluorescence microscope images of the samples are shown in Figure 20(a)-(d).

[0318] (iii) Direct contact

[0319] To investigate how endothelial cells respond when in direct contact with the developed materials, a direct contact assay was carried out. This method allowed for the assessment of the material's biocompatibility by observing potential morphological changes, adhesion capacity, and cytoskeletal organization of the cells when they are seeded directly onto the surface.

[0320] For this experiment, a new culture medium formulation was prepared, consisting of 24.5 mL of DMEM (Dulbecco's Modified Eagle Medium), 25 mL of FBS (Fetal Bovine Serum - 50%), and 500 pL of Penicillin / Streptomycin (1%). The direct contact assay used a concentrated suspension of 10.000 cells in 10 pL, equivalent to 1,000,000 cells / mL

[0321] The resulting 1 mL of diluted suspension was used to seed the samples. A volume of 12.5 pL was carefully pipetted onto the functionalized surface of each sample, after putting the samples under UV for 10 minutes for sterilization. The tested materials included:

[0322] Pure Fe disc (control) • Fe-Au-DCC-5mM-NAC20mM (without UV-induced photoactivation)

[0323] • Fe-Au-DCC-NAC-PI-5mM(UV photoactivated)

[0324] The Lab-Tek chambers were then incubated for 1 hour at 37 °C with controlled CO2 to allow proper cell adhesion. After this period, 500 pL of complete culture medium was added to each well, and the samples were incubated for an additional 72 hours before proceeding with the fixation and staining protocol as described in point (i) above.

[0325] The obtained ZEISS confocal fluorescence microscope images of the samples are shown in Figure 21(a)-(c).

[0326] It results from the three above tests that the viability and overall condition of the cells for all three experiments are excellent, which strongly suggests that the modified Fe surfaces and their released products exhibit a high biocompatibility (at least equivalent to that of pure Fe samples).

Claims

45CLAIMS1. Bioresorbable iron-based stent, wherein at least part of the stent is coated with a microgalvanic layer comprising nano- or sub-micrometric structures of a conductive material bonded to an organic primer layer, wherein the conductive material of the nano- or submicrometric structures exhibits a Standard Electrode Potential (SEP) higher than that of iron or of the iron alloy.

2. Bioresorbable iron-based stent according to claim 1, wherein the organic primer layer is formed by a coupling agent, the coupling agent comprising at least two functions, one capable of binding to the iron-based stent surface, and the other capable of binding to the nano- or submicrometric structures, the organic primer layer being obtained by contacting the stent and the nano- or sub-micrometric structures in presence of the coupling agent.

3. Bioresorbable iron-based stent according to claim 1 or claim 2, wherein the bioresorbable iron-based stent is a bioresorbable endovascular or extravascular stent, preferably a bioresorbable endovascular stent.

4. Bioresorbable iron-based stent according to any one of claims 1 to 3, wherein the conductive material of the nanostructures exhibits a SEP higher than -0.44 V.

5. Bioresorbable iron-based stent according to any one of claims 1 to 4, wherein the nano- or sub-micrometric structures of a conductive material are selected from the group consisting of particles, such as spheres, rods, tubes, cages, ribbons, rings, shells, wires, quantum dots and fibers of the conductive material.

6. Bioresorbable iron-based stent according to any one of claims 1 to 5, wherein the nano- or sub-micrometric structures are selected from the group consisting of carbon nanostructures, such as carbon nanotubes, gold nanostructures, such as gold nanoparticles, silver nanostructures, such as silver nanoparticles, platinum nanostructures, such as platinum nanoparticles, palladium nanostructures, such as palladium nanoparticles, and transition metal oxide nanostructures, such as transition metal oxide nanoparticles, preferably gold nanoparticles.

7. Bioresorbable iron-based stent according to any one of claims 1 to 6, wherein the ironbased stent is an iron stent.

468. Bioresorbable iron-based stent according to any one of claims 1 to 6, wherein the ironbased stent is an iron-alloy stent, wherein the iron alloy preferably includes Fe with at least one element selected from the group consisting of: Li, Na, P, S, K, Ca, Ti, Co, Ni, Cu, Ga, Sr, Y, Zr, Nb, Mo, Ag, Sn, I, Cs, Hf, Ba, Ge, B, O, Ta, W, Re, Os, Ir, La, Ce, Sm, Gd, Mn, C, Si, N, Zn, Mg, Pt, Pd and Au.

9. Bioresorbable iron-based stent according to claim 8, wherein the alloy comprises at least 50 at % iron before coating, preferably at least 60 at % iron, preferably at least 70 at % iron, preferably at least 80 at % iron, preferably at least 90 at % iron, more preferably at least 95 at % iron.

10. Bioresorbable iron-based stent according to any of claims 1 to 9, wherein the microgalvanic layer is present on at least 50%, preferably at least 60%, preferably at least 70%, preferably at least 80%, preferably at least 90%, preferably at least 95%, more preferably at least 99%, of the outer surface of the stent.

11. Bioresorbable iron-based stent according to any one of claims 1 to 10, wherein the organic primer layer is obtained from a coupling agent selected from the group consisting of aryldiazonium salts, siloxane compounds, including poly(ethylene glycol) (PEG) containing siloxanes, polyamines, such as polydopamine (PDA), and polyimines, such as polyethylenimine (PEI), preferably aryldiazonium salts, more preferably 4- cyanobenzenediazonium tetrafluoroborate, 4-ethynylbenzenediazonium tetrafluoroborate, 4- carboxybenzenediazonium tetrafluoroborate, 4-(aminomethyl)benzenediazonium tetrafluoroborate, and / or 4-boronobenzenediazonium tetrafluoroborate, even more preferably 4-cyanobenzenediazonium tetrafluoroborate.

12. Bioresorbable iron-based stent according to any one of claims 1 to 11, wherein the stent is an iron stent, the nano- or sub-micrometric structures are gold nanoparticles, and the organic primer layer is obtained from a coupling agent which is an aryldiazonium salt, preferably 4- cy anobenzenedi azonium tetrafluoroborate.

13. Bioresorbable iron-based stent according to any one of claims 1 to 11, wherein the nano- or sub-micrometric structures are functionalized by at least one functionalizing molecule.

14. Bioresorbable iron-based stent according to claim 13, wherein the functionalizing molecule is selected from the group consisting of an anti-oxidant, a prostacyclin receptor, and a drug, such as an anti-proliferative agent, an anti-thrombotic drug, a statin-based drug or an anti-inflammation drug, preferably an anti-oxidant.4715. Bioresorbable iron-based stent according to claim 14, wherein the anti-oxidant is selected from the group consisting of N-acetylcysteine, vitamins, such as vitamin C or E, mitochondria targeted anti-oxidants, such as MitoQ, polyunsaturated fatty acids, such as omega-3 or omega-6, polyphenol, such as flavonoid, and astaxanthine, preferably N- acetylcysteine.

16. Bioresorbable iron-based stent according to any one of claims 13 to 15, wherein the stent is an iron stent, the nano- or sub-micrometric structures are gold nanoparticles functionalized by an anti-oxidant, such as N-acetylcysteine, and wherein the organic primer layer is obtained from a coupling agent which is preferably an aryldiazonium salt, more preferably a 4-ethynylbenzenediazonium salt, such as 4-ethynylbenzenediazonium tetrafluoroborate.

17. Process for coating at least part of a bioresorbable iron-based stent, comprising a step of contacting at least part of the bioresorbable iron-based stent with an aqueous solution or suspension comprising nano- or sub-micrometric structures and / or a precursor thereof and with a precursor of an organic primer layer, wherein the nano- or sub-micrometric structures comprise a conductive material with a SEP higher than that of the ion or iron-alloy of the stent.

18. Process for coating at least part of a bioresorbable iron-based stent according to claim 17, wherein the nano- or sub-micrometric structures precursor is chloroauric acid or chloroplatinic acid.

19. Process for coating at least part of a bioresorbable iron-based stent according to claim 17 or claim 18, wherein the coupling agent is selected from the group consisting of aryldiazonium salts, siloxane compounds, including poly(ethylene glycol) (PEG) containing siloxanes, polyamines, such as polydopamine (PDA), and polyimines, such as polyethylenimine (PEI), preferably aryldiazonium salts, more preferably 4-cyanobenzenediazonium tetrafluoroborate, 4-ethynylbenzenediazonium tetrafluoroborate, 4-carboxybenzenediazonium tetrafluoroborate, 4-(aminomethyl)benzenediazonium tetrafluoroborate, and / or 4-boronobenzenediazonium tetrafluoroborate, even more preferably 4-cyanobenzenediazonium tetrafluoroborate.

20. Process for coating at least part of a bioresorbable iron-based stent according to any one of claims 17 to 19, wherein the nano- or sub-micrometric structures are functionalized by at least one functionalizing molecule, and wherein the process further comprises a step of contacting at least part of the bioresorbable iron-based stent coated by the nano- or sub-micrometric structures with an aqueous solution comprising the functionalization molecule, optionally in presence of a coupling agent.

21. Process for coating at least part of a bioresorbable iron-based stent according to claim 20, wherein the nano- or sub-micrometric structures are gold nanoparticles, the functionalizing molecule is an anti-oxidant, such as N-acetylcysteine, and the precursor of the organic primer layer is preferably 4-ethynylbenzenediazonium tetrafluoroborate.

22. Process for coating at least part of a bioresorbable iron-based stent according to any one of claims 17 to 21, wherein the concentration of the coupling agent in the aqueous solution is comprised between 0.05 mM and 10 mM, preferably between 0.1 mM and 5 mM, even more preferably is about 0.2 mM or about 5 mM.

23. Process for coating at least part of a bioresorbable iron-based stent according to any one of claims 17 to 22, wherein the concentration of the nano- or sub-micrometric structures and / or a precursor thereof in the aqueous solution is comprised between 0.01 mM and 1 mM, preferably between 0.05 mM and 0.2 mM or between 0.05 mM and 0.7 mM, even more preferably is about 0.1 mM or about 0.5 mM.

24. Process for controlling, preferably for increasing, the degradation and / or the biocompatibility of a bioresorbable iron-based stent, comprising a step of coating the stent with a microgalvanic layer comprising nano- or sub-micrometric structures of a conductive material bonded to an organic primer layer.

25. Process for controlling, preferably for increasing, the degradation and / or the biocompatibility of a bioresorbable iron-based stent according to claim 24, wherein the ironbased stent is an iron stent, the nano- or sub-micrometric structures are gold nanoparticles and the organic primer layer is obtained from a coupling agent, wherein the coupling agent is an aryldiazonium salt, preferably 4-cyanobenzenediazonium tetrafluoroborate.

26. Process for controlling, preferably for increasing, the degradation and / or the biocompatibility of a bioresorbable iron-based stent according to claim 24, wherein the ironbased stent is an iron stent, the nano- or sub-micrometric structures are gold nanoparticles functionalized by an anti-oxidant, such as N-acetylcysteine, and the organic primer layer is obtained from a coupling agent which is preferably an aryldiazonium salt, more preferably 4- ethynylbenzenediazonium tetrafluoroborate.

27. Bioresorbable iron-based stent according to any one of claims 1 to 16, or bioresorbable iron-based stent obtained by a process according to any one of claims 17 to 26, for use in thetreatment of an anomaly or a disease of a body lumen, such as an aneurysm, aortic dissections, or stenosis / thrombosis affecting coronary, peripheral, or renal arteries / veins, and luminal obstructions due to either intrinsic disease or extrinsic pressure in the esophagus, colon, or bile duct.

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