Self-temperature-controlled magnetic heat support and preparation method thereof

Abstract

The application discloses a self-temperature-control magnetic heat support and a preparation method thereof, and belongs to the fields of magnetic materials, magnetic heat therapy technology, implantable medical devices and magnetic-heat-flow-force multi-physical field coupling numerical simulation technology. The self-temperature-control magnetic heat support is used for inhibiting post-PCI vascular restenosis. The magnetic heat support is a tubular grid structure, a plurality of unit rings which are sequentially connected and arranged in an axial direction form the tubular grid structure, and adjacent unit rings are staggered in a circumferential direction and are connected through connecting sections. A ternary alloy system taking Fe-Ni-Cr as the base is used as the main material of the magnetic support, and the mass percentage of the ternary alloy system is as follows: Fe 44.22%-45.06%, Ni 44.94%-45.78% and Cr 10%. The self-temperature-control magnetic heat support has the advantages of temperature controllability, strong target property and high system integration degree.

Description

Technical Field

[0001] This invention belongs to the fields of magnetic materials and magnetothermal therapy technology, implantable medical devices, and numerical simulation technology of multi-physics field coupling of magneto-thermal-fluid-force, and particularly relates to a self-temperature-controlled magnetothermal stent and its preparation method. Background Technology

[0002] Percutaneous coronary intervention (PCI) has become a crucial method for revascularization in the treatment of atherosclerosis due to its minimally invasive nature and proven clinical effectiveness. However, the local mechanical traction and endothelial damage introduced by stent implantation are often accompanied by an inflammatory cascade, phenotypic transformation and abnormal proliferation and migration of vascular smooth muscle cells (VSMCs), inducing platelet adhesion and aggregation and thrombus formation, ultimately leading to in-stent restenosis (ISR). Increasing experimental evidence suggests that local hyperthermia within a strictly controlled temperature window can simultaneously intervene in the excessive proliferation of VSMCs and thrombus-related processes, thereby reducing the risk of restenosis. Based on the advantages of reliable efficacy, strong targeting, and relatively few side effects of hyperthermia, a novel magnetothermal stent has been developed. This stent uses an alternating magnetic field (AMF) to induce local heating of the stent, effectively inhibiting the proliferation of VSMCs and playing a vital role in preventing stent restenosis.

[0003] Starting from the core mechanism of ISR (Intima-Stenosis Restenosis), namely, intimal hyperplasia caused by excessive proliferation of VSMCs and mural thrombus formation induced by endothelial damage after stent implantation, multiple in vitro studies have demonstrated that stent hyperthermia can inhibit excessive smooth muscle cell proliferation, and that increased temperature can reduce platelet aggregation, thereby reducing the incidence of restenosis. However, it also faces key bottlenecks in clinical translation: excessively high temperatures may induce endothelial cell apoptosis, thus affecting the process of stent endothelialization after PCI, and there are challenges in accurately monitoring and controlling the temperature, as well as the lack of standard clinical techniques for in vivo stent temperature measurement. Therefore, achieving a stable and accurate hyperthermic temperature window is a core challenge that stent hyperthermia must overcome before it can be applied clinically. A promising solution is to enable the stent to have self-regulating temperature performance, allowing the temperature of the target hyperthermic area to be limited within a safe and effective hyperthermic window without the need for complex in vivo temperature measurement and closed-loop control. Previous studies have shown that low Curie temperature (TC) magnetic systems can exhibit temperature self-stabilizing behavior under AMF (Amphipathic Fiber). From the perspective of material thermophysics and magnetic mechanism, the support structure made of low TC alloy can transform from ferromagnetism to paramagnetism when close to TC, which significantly reduces magnetic loss and thus achieves heating self-limitation. Theoretically, the peak temperature can be limited to below TC.

[0004] However, low-TC metal systems often face new problems after stent formation: how to improve the heating rate, expand the effective thermotherapy volume and achieve axial temperature uniformity while ensuring mechanical support and blood flow compatibility still needs to be solved through integrated material-structure design. Optimization of stent topology plays a key role in this process. Summary of the Invention

[0005] In view of this, the present invention discloses a self-temperature-controlled magnetothermal support and its preparation method.

[0006] The present invention adopts the following technical solution: A self-temperature-controlled magnetothermal stent is disclosed, which is used to inhibit restenosis after PCI. The magnetothermal stent has a tubular mesh structure, in which multiple unit rings are connected sequentially along the axial direction to form the tubular mesh structure. Adjacent unit rings are staggered in the circumferential direction and connected by connecting segments. The magnetothermal stent uses a Fe-Ni-Cr based ternary alloy system as the main magnetic stent material, and the mass proportions of the ternary alloy system are: Fe 44.22%~45.06%, Ni 44.94%~45.78%, and Cr 10%.

[0007] Furthermore, the unit ring is a periodic waveform structure, and the unit ring is formed by multiple repeating units connected end to end to form a closed loop in the circumferential direction; each repeating unit contains at least one peak and one valley, and the connection between adjacent peaks and valleys forms a turning point. Multiple repeating units form a rhomboid grid unit, so that the support forms a closed loop skeleton.

[0008] Furthermore, adjacent unit rings are connected by connecting segments, which are connected to the turning points.

[0009] Furthermore, the magnetothermal support is composed of support wires with a width of th. The unit rings have different ring heights in different axial regions. The ring height of the proximal unit ring is hs1, and the ring height of the distal unit ring is hs2. The hs1 ring height unit ring and the hs2 ring height unit ring account for 3 / 8 and 5 / 8 of the total number of unit rings, respectively, and the ring height hs1 > hs2.

[0010] Furthermore, the dimensions of the magnetothermal support include: an outer diameter of 2-6 mm, a thickness of 0.05-0.2 mm, a length of 12-14.5 mm, a support wire width of th of 0.07 mm-0.20 mm, ring heights hs1 and hs2 of 1.20 mm-2.25 mm, and a ring density Ns of 6-13; the ring density Ns is the number of repeating units in the circumferential direction.

[0011] Furthermore, the magnetothermal stent can be radially deployed via balloon expansion or an equivalent method.

[0012] A method for preparing the above-mentioned self-temperature-controlled magnetocaloric scaffold, the method comprising the following steps: S1) Determine the Curie temperature range of the magnetic stent: Determine the thermotherapy temperature window; Based on the thermotherapy temperature window, and considering the temperature gradient caused by uneven blood flow cooling, derive and determine the required Curie temperature range for the magnetic stent material. S2) Screening of alloy systems for synergistic biomedical and magnetocaloric functions: Based on the Curie temperature range described in S1, a ternary alloy system based on Fe-Ni-Cr was selected as the main material for the magnetic scaffold. S3) Material composition ratio: Based on the CALPHAD method of multi-element phase diagram calculation, the phase stability, order-disorder transition and magnetic phase transition temperature of the ternary alloy system described in S2 are calculated in high throughput. Combined with experimental verification, the composition ratio of the material components of the ternary alloy system is determined. S4) Support structure design: The magnetothermal support is a tubular mesh structure, and multiple unit rings connected in sequence along the axial direction constitute the tubular mesh structure. Adjacent unit rings are staggered in the circumferential direction and connected by connecting segments. S5) Manufacturing of the magnetothermal support: The materials in the composition ratio described in S3 are sequentially melted into metal, cast into shape, hot-working and heat-treated after casting, and then drawn to obtain a metal capillary. The magnetothermal support described in S4 is then obtained by femtosecond laser etching and polished.

[0013] Furthermore, the thermotherapy temperature window described in S1 is 43~46℃.

[0014] Furthermore, the magnetic thermal stent-assisted control method includes: a safety monitoring and emergency termination mechanism: a dual safety guarantee is set up, relying on the self-temperature control characteristics of the magnetic thermal stent, and an infrared thermal imager is simultaneously activated to perform real-time imaging of the temperature of the target blood vessel area; the AMF generator is interlocked with the electrocardiogram monitoring system; and an emergency stop button is set up to terminate the hyperthermia.

[0015] Compared with the prior art, the present invention has the following beneficial effects: This invention achieves safe, effective, and precise intervention for vascular restenosis after PCI through synergistic optimization of stent material composition design, stent structure design, and magnetothermal therapy implementation. In terms of material design, an Fe-Ni-Cr based alloy is selected as the main material of the magnetic stent. Fe provides high magnetic response and heating capacity, Ni is used to regulate the Curie point and improve material ductility, and Cr is used to improve corrosion resistance and biomedical applicability. The material composition range is determined by combining Slater-Pauling's law and CALPHAD calculations, ensuring that the stent's Curie point matches the effective temperature window of 43-46℃ for thermotherapy. This gives the stent self-temperature-regulating characteristics under the influence of an alternating magnetic field, enabling passive and precise control of the thermotherapy temperature without the need for complex in vivo temperature measurement and closed-loop control, significantly reducing the risk of local overheating damage.

[0016] In terms of structural design, a tubular mesh stent structure is adopted. Through the combination design of unit rings, connecting structures and diamond closed-loop mesh, and combined with the adjustment of parameters such as support width, ring height and ring density, the radial support performance is guaranteed while taking into account axial flexibility, wall adhesion and delivery. At the same time, the optimization of structural parameters helps to improve the stent's heating characteristics and temperature distribution uniformity under blood flow scouring conditions, thereby improving the effective coverage and heating stability of the hyperthermia area.

[0017] Regarding the effects of magnetothermal therapy, this invention can rapidly raise the temperature at the stent implantation site to the effective temperature range required to inhibit restenosis under the action of an alternating magnetic field, allowing heat to act directly on the blood vessel wall, achieving local, in situ, and targeted treatment. Experimental results show that while effectively inhibiting the proliferation of vascular smooth muscle cells, this invention does not significantly affect the proliferation capacity of endothelial cells. Smooth muscle cell proliferation decreased by 32.8% within 6 days, indicating that it has the dual advantages of inhibiting intimal hyperplasia and protecting endothelial repair, thereby helping to reduce the risk of in-stent restenosis.

[0018] Furthermore, this invention combines intraoperative stent positioning with precise postoperative application of alternating magnetic fields, which allows the thermotherapy effect to be concentrated on the blood vessel segment where the stent is located. It has the advantages of strong targeting, accurate temperature control, effective inhibition of proliferation, minimal impact on surrounding normal tissues, and high feasibility of clinical application. Attached Figure Description

[0019] To more clearly illustrate the technical solutions of the embodiments of the present invention, the drawings used in the embodiments will be briefly introduced below. Obviously, the drawings described below are only some embodiments of the present invention. For those skilled in the art, other drawings can be obtained based on these drawings without creative effort.

[0020] Figure 1 This is a schematic diagram of determining the TC value using the MT curve of the VSM magnetic support in an embodiment of the present invention; Figure 2 This is a schematic diagram of the stent structure design in an embodiment of the present invention, with an inner diameter of 2mm, a stent support wire th of 0.2mm, hs1=2.25mm and hs1 being the first 5 loops at the proximal end, hs2=1.75mm and hs2 being the first 9 loops at the distal end, and Ns=9. Figure 3 This is a schematic diagram of the support position image and the thermal image during the experiment in an embodiment of the present invention; Figure 4 In this embodiment of the invention, when Q=63.6 ml / min and H=18 kA / m, T in With T out Schematic diagram of the curve changing over time; Figure 5 In this embodiment of the invention, when Q=84.8 ml / min and H=18 kA / m, T in With T out Schematic diagram of the curve changing over time; Figure 6 In this embodiment of the invention, when Q=127.2 ml / min and H=18 kA / m, T in With T out Schematic diagram of the curve changing over time; Figure 7 A schematic diagram illustrating the method of inhibiting stent restenosis after PCI using a self-controlled temperature magnetic stent thermotherapy in an embodiment of the present invention; Figure 8 A schematic diagram of the cell morphology of smooth muscle cells and endothelial cells under an electron microscope after 144 hours of magnetic hyperthermia in the control, thermotherapy and magnetothermal therapy groups in this embodiment of the invention. Figure 9 A schematic diagram of smooth muscle cell counts in the control, thermotherapy, and magnetothermal therapy groups after 0h, 48h, 96h, and 144h of magnetothermal therapy in this embodiment of the invention; Figure 10 A schematic diagram of endothelial cell counts in the control, thermotherapy, and magnetothermal therapy groups after 0h, 48h, 96h, and 144h of magnetothermal therapy in this embodiment of the invention; Figure 11 Representative images of HE staining of blood vessels in the control and experimental groups, as well as schematic diagrams of quantitative analysis results, are shown in the embodiments of this invention. Figure 12 Representative images of CD68 and α-SMA staining in blood vessels of the control and experimental groups, and schematic diagrams of quantitative analysis results, in this embodiment of the invention; Figure 13The blood lipid biochemical detection of control and experimental group animals in the embodiments of this invention includes a schematic diagram of the concentrations of total cholesterol (TC), triglycerides (TG), high-density lipoprotein cholesterol (HDL-C) and low-density lipoprotein cholesterol (LDL-C). Detailed Implementation

[0021] To better understand the technical solution of the present invention, the embodiments of the present invention will be described in detail below with reference to the accompanying drawings. It should be understood that the described embodiments are only some embodiments of the present invention, and not all embodiments.

[0022] Example 1

[0023] A self-temperature-controlled magnetothermal stent is disclosed, which is used to inhibit restenosis after PCI. The magnetothermal stent has a tubular mesh structure, in which multiple unit rings are connected sequentially along the axial direction to form the tubular mesh structure. Adjacent unit rings are staggered in the circumferential direction and connected by connecting segments. The magnetothermal stent uses a Fe-Ni-Cr based ternary alloy system as the main magnetic stent material, and the mass proportions of the ternary alloy system are: Fe 44.22%~45.06%, Ni 44.94%~45.78%, and Cr 10%.

[0024] Furthermore, the unit ring described in S4 has a periodic waveform ("V"-shaped repeating unit) structure, with multiple repeating units connected end-to-end to form a closed loop along the circumference of the unit ring; each repeating unit includes at least one peak and one valley, with the connection between adjacent peaks and valleys forming a turning point, and multiple repeating units forming a rhomboid grid unit, thus creating a closed-loop skeleton for the support. The combination of multiple peaks and valleys further improves the flexibility of the support in use.

[0025] Furthermore, adjacent unit rings are connected by connecting segments, which are connected to the turning points.

[0026] Furthermore, the magnetothermal stent is composed of support wires with a width of th. The unit rings have different ring heights in different axial regions. The ring height of the proximal end (blood flow inlet) unit ring is hs1, and the ring height of the distal end (blood flow outlet) unit ring is hs2. The hs1 ring height unit ring and the hs2 ring height unit ring account for 3 / 8 and 5 / 8 of the total number of unit rings, respectively, and the ring height hs1>hs2.

[0027] Furthermore, the dimensions of the magnetothermal stent include: an outer diameter of 2-6 mm, a thickness (thickness of the magnetothermal stent wall) of 0.05-0.2 mm, a length of 12-14.5 mm, a strut wire width of th of 0.07 mm-0.20 mm, ring heights hs1 and hs2 of 1.20 mm-2.25 mm, and a ring density Ns of 6-13; the ring density Ns is the number of repeating units in the circumferential direction. By using different ring heights and proportions of rings with different ring heights in different axial regions, and by setting the dimensions of the magnetothermal stent, a designable balance can be achieved between the "radial support, axial compliance, and bending passability" of the magnetothermal stent, which can significantly improve the delivery and deformation capabilities under complex vascular pathways, and the practical application effect is significant.

[0028] Furthermore, the magnetothermal stent can be radially deployed via balloon expansion or an equivalent method.

[0029] A method for preparing the above-mentioned self-temperature-controlled magnetocaloric scaffold, the method comprising the following steps: S1) Determine the Curie temperature range of the magnetic stent: Determine a safe and effective thermotherapy temperature window that can significantly inhibit abnormal activation of VSMCs without damaging endothelial regeneration capacity; Based on the thermotherapy temperature window, and considering the temperature gradient caused by uneven blood flow cooling, derive and determine the Curie temperature range required for the magnetic stent material; Ensure that the vessel wall temperature can still be maintained above the effective thermotherapy threshold under the most unfavorable blood flow conditions without damaging endothelial cells. S2) Screening of alloy systems for biomedical and magnetocaloric synergy: Based on the Curie temperature range described in S1, a ternary alloy system based on Fe-Ni-Cr was selected as the main material of the magnetic scaffold. Fe provides high saturation magnetization to enhance magnetocaloric efficiency, Ni is used to adjust the Curie temperature and improve ductility, and Cr significantly improves the material's resistance to pitting corrosion and passivation in the blood environment. S3) Material composition ratio: Based on the CALPHAD method of multi-element phase diagram calculation, the phase stability, order-disorder transition and magnetic phase transition temperature of the ternary alloy system described in S2 are calculated in high throughput. Combined with experimental verification, the composition ratio of the material components of the ternary alloy system is determined, so as to realize the passive self-controlled temperature rise characteristics without external control. S4) Support structure design: The magnetothermal support is a tubular mesh structure, and multiple unit rings connected in sequence along the axial direction constitute the tubular mesh structure. Adjacent unit rings are staggered in the circumferential direction and connected by connecting segments; each unit ring includes a wave-shaped support column that undulates periodically in the circumferential direction, and the wave-shaped support column forms multiple crowns; S5) Manufacturing of the magnetothermal support: The materials in the composition ratio described in S3 are sequentially melted into metal, cast into shape, hot-working and heat-treated after casting, and then drawn to obtain a metal capillary. The magnetothermal support described in S4 is then obtained by femtosecond laser etching and polished.

[0030] Furthermore, the thermotherapy temperature window described in S1 is 43~46℃.

[0031] Furthermore, the magnetic thermal stent-assisted control method includes: a safety monitoring and emergency termination mechanism: a dual safety guarantee is set up, relying on the self-temperature control characteristics of the magnetic thermal stent, and an infrared thermal imager is simultaneously activated to perform real-time imaging of the temperature of the target blood vessel area; the AMF generator is interlocked with the electrocardiogram monitoring system; and an emergency stop button is set up to terminate the hyperthermia.

[0032] Example 2

[0033] A self-controlled temperature magnetic stent thermotherapy method and a magnetic thermal stent for inhibiting restenosis after PCI, comprising the following steps: S1) Determine the Curie temperature range of the magnetic stent: Determine a safe and effective thermotherapy temperature window that can significantly inhibit abnormal activation of VSMCs without damaging endothelial regeneration capacity; Considering the temperature gradient caused by uneven blood flow cooling, derive the Curie temperature range required for the magnetic stent material to ensure that the vessel wall temperature can still be maintained above the effective thermotherapy threshold under the most unfavorable blood flow conditions without damaging endothelial cells. S2) Screening of alloy systems for biomedical and magnetocaloric synergy: Fe-Ni-Cr based ternary alloy system was selected as the main material of magnetic scaffold. Fe provides high saturation magnetization to enhance magnetocaloric efficiency, Ni is used to adjust Curie temperature and improve ductility, and Cr significantly improves the material’s resistance to pitting corrosion and passivation in the blood environment. S3) Material composition ratio: Based on the CALPHAD method of multivariate phase diagram calculation, the phase stability, order-disorder transition and magnetic phase transition temperature of the Fe-Ni-Cr system are calculated in high throughput. Combined with experimental verification, the material composition and ratio range of the magnetic support are determined to achieve passive self-controlled temperature rise characteristics without external control. S4) Stent structure design: The stent is a tubular mesh structure. The vascular stent is mainly composed of multiple unit ring structures arranged sequentially along the axial direction and connecting structures connecting adjacent unit rings. It adopts a rhomboid closed-loop mesh unit. Adjacent unit ring structures are staggered in the circumferential direction and are formed into a continuous whole through connecting segments. Each ring support unit is composed of wave-shaped pillars that undulate periodically along the circumferential direction and form multiple coronary parts. The stent is an intravascular implant that can be radially expanded by balloon expansion or equivalent means. S5) Magnetic stent manufacturing: According to the material composition and proportion in S3), the metal is melted, cast, and then hot-worked and heat-treated. It is drawn into a metal capillary and then processed into a magnetic vascular stent with the structure of S4) by femtosecond laser etching and polished. S6) Determination of magnetothermal therapy parameters based on Curie temperature matching: Determine the thermotherapy parameters such as the intensity, frequency and duration of the alternating magnetic field, to ensure that the stent rapidly heats up to the thermotherapy temperature value under the excitation of the alternating magnetic field (AMF). S7) Stent implantation and intraoperative positioning confirmation: The Fe-Ni-Cr based self-temperature controlled magnetic stent described in S5 is loaded into a balloon catheter and delivered to the target lesion site via the radial or femoral artery. Under angiography guidance, the stent is released and adhered to the wall to ensure that the stent completely covers the lesion segment, adheres well to the wall, and there is no geographical loss or edge dissection. High-pressure post-dilation is performed immediately after the procedure (if necessary), and the initial and final positions of the stent are marked for surface positioning during subsequent AMF application. S8) Immediate and precise application of alternating magnetic field after surgery: Within 30 minutes after successful stent implantation, the patient is transferred to the hyperthermia area equipped with a dedicated AMF generator. Based on the stent position marked by intraoperative DSA images, the patient's target vessel is placed in the central area of ​​the dedicated AMF generator. The water-cooled AMF generator is turned on, and an alternating magnetic field is applied according to the parameters determined in S6). Under the action of AMF, the magnetic stent generates heat through eddy current and hysteresis mechanisms, causing the local temperature of the vessel wall to rise rapidly to the effective temperature for preventing restenosis. The safe and effective temperature window for hyperthermia in S1) that can significantly inhibit abnormal activation of VSMCs without damaging endothelial regeneration capacity is 43~46℃.

[0034] The target Curie point metal material composition in S4) is: Fe 44.22%~45.06%, Ni 44.94%~45.78% and Cr 10%.

[0035] The shape of the magnetothermal support in S4) is as follows: each unit ring is a periodic waveform ("V"-shaped repeating unit) structure, with multiple repeating units connected end-to-end to form a closed loop along the circumference; each repeating unit contains at least one peak and at least one valley, with turning points formed at the peaks / valleys; multiple repeating units form a rhomboid grid unit, making the support a closed-loop skeleton; adjacent unit rings are connected by several connecting segments, which are connected to the turning points of the unit rings, thereby coupling the circumferential waveform structure and the axial structure into one; the support is composed of The stent is constructed with struts of width th. The unit rings can have different ring heights in different axial regions. The height of the support ring at the proximal end (blood flow inlet) is hs1, and the height of the support ring at the distal end (blood flow outlet) is hs2. hs1 and hs2 account for approximately 3 / 8 and 5 / 8 of the total number of support rings, respectively, with hs1 > hs2. The number of circumferential repeating units is Ns (i.e., the 360° circumference is divided into Ns repeating units), used to adjust the grid density and radial support capacity. The larger th and Ns are, the higher the stent's heating efficiency. By setting different ring heights axially, zoned mechanical and compliance design can be achieved. By adjusting parameters such as th, hs1, hs2, and Ns, a designable balance can be achieved between radial support, axial compliance, and bending passability. For example, increasing Ns or th can improve support and coverage uniformity, and setting hs1 / hs2 in different axial segments can achieve differentiated compliance and wall adhesion, thereby improving delivery and deformation capabilities in complex vascular pathways.

[0036] The dimensions of the magnetothermal support in S4) are: outer diameter 2~6 mm, thickness 0.05~0.2 mm, length 12~14.5 mm, support width th 0.07 mm~0.20 mm, ring height hs1 and hs2=1.20 mm~2.25 mm, and ring density Ns=6~13.

[0037] The thermotherapy parameters in S6) are determined as follows: thermotherapy time 30 min, frequency range of external alternating magnetic field 287 kHz~500 kHz, and magnetic field strength 12~30 kA / m.

[0038] The magnetic thermal vascular stent is used to inhibit coronary artery restenosis, with the average temperature of the vessel wall exceeding 43°C during the hyperthermia process.

[0039] Under the S6) thermotherapy parameters, it can inhibit the proliferation of smooth muscle cells without affecting the proliferation capacity of endothelial cells. Within 6 days, the proliferation of smooth muscle cells decreased by 32.8%.

[0040] An adjunctive control strategy for inhibiting restenosis after PCI using a self-controlled temperature magnetic stent thermotherapy method includes the following steps: S1) Safety monitoring and emergency termination mechanism for hyperthermia: Although relying on the self-temperature control characteristics of the material, dual safety protection can be set up. The infrared thermal imager is activated simultaneously to image the temperature of the target blood vessel area in real time. If abnormal temperature fluctuations occur, an audible and visual alarm is automatically triggered. The AMF generator is interlocked with the patient's electrocardiogram monitoring system. If arrhythmia (such as premature ventricular contractions or ST segment elevation) is detected, the AMF output is immediately cut off. The operating physician can also press the emergency stop button at any time to terminate the hyperthermia. S2) Individualized adjustment and repetition strategy of hyperthermia dosage: Dynamically fine-tune the AMF field intensity to compensate for heat loss based on the patient's weight, chest wall thickness or blood flow velocity (intraoperative FFR / iFR value). For patients with high restenosis risk (such as diabetes, small vessel disease), an additional adjuvant hyperthermia can be added within 24 hours after surgery, with parameters of 80% intensity and 10 minutes as the first time, to prolong the anti-cell proliferation effect.

[0041] Example 3

[0042] like Figure 1 As shown, a self-controlled temperature magnetic stent thermotherapy method and a magnetic thermostatic stent for inhibiting restenosis after PCI are disclosed. The method specifically includes the following steps: S1) Determine the Curie temperature range of the magnetic stent: Determine a safe and effective thermotherapy temperature window that can significantly inhibit abnormal activation of VSMCs without damaging endothelial regeneration capacity; Considering the temperature gradient caused by uneven blood flow cooling, derive the Curie temperature range required for the magnetic stent material to ensure that the vessel wall temperature can still be maintained above the effective thermotherapy threshold under the most unfavorable blood flow conditions without damaging endothelial cells. S2) Screening of alloy systems for biomedical and magnetocaloric synergy: Fe-Ni-Cr based ternary alloy system was selected as the main material of magnetic scaffold. Fe provides high saturation magnetization to enhance magnetocaloric efficiency, Ni is used to adjust Curie temperature and improve ductility, and Cr significantly improves the material’s resistance to pitting corrosion and passivation in the blood environment. S3) Material composition ratio: Based on the CALPHAD method of multivariate phase diagram calculation, the phase stability, order-disorder transition and magnetic phase transition temperature of the Fe-Ni-Cr system are calculated in high throughput. Combined with experimental verification, the material composition and ratio range of the magnetic support are determined to achieve passive self-controlled temperature rise characteristics without external control. S4) Stent structure design: The stent is a tubular mesh structure. The vascular stent is mainly composed of multiple unit ring structures arranged sequentially along the axial direction and connecting structures connecting adjacent unit rings. It adopts a rhomboid closed-loop mesh unit. Adjacent unit ring structures are staggered in the circumferential direction and are formed into a continuous whole through connecting segments. Each ring support unit is composed of wave-shaped pillars that undulate periodically along the circumferential direction and form multiple coronary parts. The stent is an intravascular implant that can be radially expanded by balloon expansion or equivalent means. S5) Magnetic stent manufacturing: According to the material composition and proportion in S3), the metal is melted, cast, and then hot-worked and heat-treated. It is drawn into a metal capillary and then processed into a magnetic vascular stent with the structure of S4) by femtosecond laser etching and polished. S6) Determination of magnetothermal therapy parameters based on Curie temperature matching: Determine the thermotherapy parameters such as the intensity, frequency and duration of the alternating magnetic field, to ensure that the stent rapidly heats up to the thermotherapy temperature value under the excitation of the alternating magnetic field (AMF). S7) Stent implantation and intraoperative positioning confirmation: The Fe-Ni-Cr based self-temperature controlled magnetic stent described in S5 is loaded into a balloon catheter and delivered to the target lesion site via the radial or femoral artery. Under angiography guidance, the stent is released and adhered to the wall to ensure that the stent completely covers the lesion segment, adheres well to the wall, and there is no geographical loss or edge dissection. High-pressure post-dilation is performed immediately after the procedure (if necessary), and the initial and final positions of the stent are marked for surface positioning during subsequent AMF application. S8) Immediate and precise application of alternating magnetic field after surgery: Within 30 minutes after successful stent implantation, the patient is transferred to the hyperthermia area equipped with a dedicated AMF generator. Based on the stent position marked by intraoperative DSA images, the patient's target vessel is placed in the central area of ​​the dedicated AMF generator. The water-cooled AMF generator is turned on, and an alternating magnetic field is applied according to the parameters determined in S6). Under the action of AMF, the magnetic stent generates heat through eddy current and hysteresis mechanisms, causing the local temperature of the vessel wall to rise rapidly to the effective temperature for preventing restenosis. Furthermore, the temperature window for safe and effective hyperthermia in S1) that can significantly inhibit abnormal activation of VSMCs without damaging endothelial regeneration capacity is 43~46℃.

[0043] Furthermore, the target Curie point metal material composition in S4) is: Fe 44.22%~45.06%, Ni 44.94%~45.78% and Cr 10%.

[0044] Furthermore, the shape of the magnetothermal support in S4) is as follows: each unit ring is a periodic waveform ("V"-shaped repeating unit) structure, with multiple repeating units connected end-to-end to form a closed loop along the circumference; each repeating unit includes at least one peak and at least one valley, with turning points formed at the peaks / valleys; multiple repeating units form a rhomboid grid unit, making the support a closed-loop skeleton; adjacent unit rings are connected by several connecting segments, which are connected to the turning points of the unit rings, thereby coupling the circumferential waveform structure and the axial structure into one; The stent is composed of strut wires with a width of th. The unit rings can have different ring heights in different axial regions. The height of the support ring at the proximal end (blood flow inlet) is hs1, and the height of the support ring at the distal end (blood flow outlet) is hs2. hs1 and hs2 account for approximately 3 / 8 and 5 / 8 of the total number of support rings, respectively, with hs1 > hs2. The number of circumferential repeating units is Ns (i.e., the 360° circumference is divided into Ns repeating units), used to adjust the grid density and radial support capacity. The larger th and Ns are, the higher the stent's heating efficiency. By setting different ring heights in the axial direction, zoned mechanical and compliance design can be achieved. By adjusting parameters such as th, hs1, hs2, and Ns, a designable balance can be achieved between radial support, axial compliance, and bending passability. For example, increasing Ns or th can improve support and coverage uniformity, and setting hs1 / hs2 in different axial segments can achieve differentiated compliance and wall adhesion, thereby improving delivery and deformation capabilities in complex vascular pathways.

[0045] Furthermore, in S4), the dimensions of the magnetothermal support in this method are: outer diameter 2~6 mm, thickness 0.05~0.2 mm, length 12~14.5 mm, support width th 0.07 mm~0.20 mm, ring height hs1 and hs2 = 1.20 mm~2.25 mm, and ring density Ns = 6~13.

[0046] Furthermore, the thermotherapy parameters in S6) are determined as follows: thermotherapy time of 30 min, frequency range of external alternating magnetic field of 287 kHz to 500 kHz, and magnetic field strength of 12 to 30 kA / m.

[0047] Furthermore, in the application of the magnetic thermal vascular stent in inhibiting coronary artery restenosis, the average temperature of the vessel wall during the hyperthermia process is higher than 43°C.

[0048] Furthermore, under the S6) thermotherapy parameters, it can inhibit the proliferation of smooth muscle cells without affecting the proliferation capacity of endothelial cells, and the proliferation of smooth muscle cells decreased by 32.8% within 6 days.

[0049] Another technical solution provided by this invention is an auxiliary control strategy for a self-controlled temperature magnetic stent thermotherapy method to inhibit restenosis after PCI, characterized by comprising the following steps: S1) Safety monitoring and emergency termination mechanism for hyperthermia: Although relying on the self-temperature control characteristics of the material, dual safety protection can be set up. The infrared thermal imager is activated simultaneously to image the temperature of the target blood vessel area in real time. If abnormal temperature fluctuations occur, an audible and visual alarm is automatically triggered. The AMF generator is interlocked with the patient's electrocardiogram monitoring system. If arrhythmia (such as premature ventricular contractions or ST segment elevation) is detected, the AMF output is immediately cut off. The operating physician can also press the emergency stop button at any time to terminate the hyperthermia. S2) Individualized adjustment and repetition strategy of hyperthermia dosage: Dynamically fine-tune the AMF field intensity to compensate for heat loss based on the patient's weight, chest wall thickness or blood flow velocity (intraoperative FFR / iFR value). For patients with high restenosis risk (such as diabetes, small vessel disease), an additional adjuvant hyperthermia can be added within 24 hours after surgery, with parameters of 80% intensity and 10 minutes as the first time, to prolong the anti-cell proliferation effect.

[0050] Example 4

[0051] A self-controlled temperature magnetic stent thermotherapy method for preventing restenosis after PCI, the method is as follows: This method induces a Fe-based magnetic alloy vascular stent to reach and remain stable within a specific temperature range using an external magnetic field. By utilizing the inhibited proliferation of smooth muscle cells in the blood vessel at this temperature, it aims to suppress restenosis after PCI. The Slater-Pauling rule is introduced as a rapid screening criterion for magnetic properties, and the phase stability of the Fe-Ni-Cr system is verified using the CALPHAD multivariate phase diagram to determine the material composition and proportions of the self-temperature-controlled stent. By designing the stent's topology, excellent heating characteristics and uniform temperature distribution are achieved. In vitro cell experiments and in vivo animal experiments are combined to determine the magnetic field parameters and temperature control strategy, verifying the effectiveness and safety of the approach. This invention has advantages such as controllable temperature, strong targeting, and high system integration. Specifically, it includes the following steps: (1) Determine the composition and proportion of vascular stent materials. In the design of biomedical scaffold materials, biocompatibility, mechanical support, and corrosion resistance are considered as fundamental constraints, while the self-regulating thermocrystal response near body temperature is taken as a functional objective. Considering that ferromagnetic phase transitions can provide a "self-limiting temperature" mechanism for induction heating, we selected an Fe-Ni-Cr based alloy system: Fe and Ni provide ferromagnetism and tunable magnetic response, while Cr is mainly used to improve corrosion resistance. Therefore, Cr was fixed at 10.0 wt% as a "low Cr design point" that balances corrosion resistance and the designability of the thermocrystal function, and the target TC was precisely located by adjusting the Fe / Ni ratio. Subsequently, the Slater-Pauling rule was introduced as a rapid screening criterion for magnetic properties, and the phase stability of the Fe-Ni-Cr system was checked using the multi-element phase diagram CALPHAD. Finally, the target Curie point metal material composition was determined to be Fe 45.06%, Ni 44.94%, and Cr 10%, and the TC was defined as 43.35℃ by measuring the MT curve using VSM and defining the tangent. Figure 1 ).

[0052] (2) In vitro experiments In this embodiment, a support structure was fabricated using Fe-44.94Ni-10Cr as the material (Curie point temperature 43.35℃). The support structure is as follows: Figure 2 As shown, the scaffold's heating effect was verified through in vitro experiments. The infrared thermal images from the experiment are shown below. Figure 3 As shown, the inlet and outlet temperatures for the three flow rates are as follows: Figure 4-6 As shown in the figure. The results show that the magnetothermal stent has better heating characteristics, and the uniformity of temperature distribution of the stent is significantly improved. Among the three flow rates used in the experiment, the temperature difference between the outer wall of the blood vessel before and after the stent was reduced by 40%-62.07%, and the outlet temperature was significantly improved (0.5℃-1.1℃, which decreased with the increase of flow rate).

[0053] (3) Cell experiments A magnetothermal integrated experimental device was constructed to determine the effects of magnetic scaffold hyperthermia on the proliferation and activity of endothelial cells and vascular smooth muscle cells (VSMCs). Figure 7 Vascular smooth muscle cells (VSMCs) and endothelial cells were seeded in 24-well tissue culture plates and cultured at 37°C in a 5% CO2 incubator until 50% confluence. Experimental cells were starved for 3 days in medium containing 0.1% fetal bovine serum (FBS), then stimulated with growth medium (5% FBS), followed by heat treatment (43°C, 30 min) 2 hours after stimulation (when the inhibition of VSMC proliferation was most significant), and then cultured at 37°C. Untreated VSMCs were maintained at 37°C. Cells were collected immediately after heat stimulation, and at 48 h, 96 h, and 144 h afterward by trypsin digestion and counted using a CDA500 particle analyzer. Figure 8Electron microscopy reveals the cell morphology of smooth muscle cells and endothelial cells in the control, thermotherapy, and magnetothermal therapy groups after 144 hours of magnetothermal therapy. Endothelial cells in all three groups were fully spread out and tightly interconnected, indicating good cell activity. The density of smooth muscle cells was lower than that of endothelial cells after 144 hours of thermotherapy and magnetothermal therapy. Throughout the study period, the number of smooth muscle cells treated with thermotherapy and magnetothermal therapy was consistently suppressed compared to the control group, decreasing by 37.5% and 32.8%, respectively. Figure 9 Furthermore, the hyperthermia group exhibited stronger inhibition, which may be due to the rapid activation of HSF1 (heat shock factor) induced by AMF. This is a crucial early step in initiating the protective response of HSPs (such as HSP70) in cells, and HSP-related responses in many systems can lead to anti-apoptotic, pro-repair, and stress tolerance effects. However, the number of endothelial cells remained relatively stable within 96 hours without significant changes. Figure 10 ).

[0054] (4) Animal experiments Magnetothermal scaffold hyperthermia was performed on a New Zealand white rabbit model to verify its in vivo efficacy in inhibiting ISR. New Zealand white rabbits were randomly divided into two groups: a control group and a magnetothermal group, with 3 rabbits in each group (n=3), for a total of 6 rabbits. Magnetothermal scaffolds were implanted in both groups. The control group did not receive magnetothermal treatment post-surgery, receiving only routine feeding and medication. For the 3 animals in the magnetothermal group, magnetothermal treatment was administered post-surgery with an alternating magnetic field frequency of 287 kHz and a magnetic field strength of 18 kA / m for 30 minutes. The control group animals were not exposed to the magnetic field but underwent the same handling and fixation conditions to eliminate errors caused by operational stress. Animals in both the experimental and control groups were euthanized and their tissues were harvested 3 months after magnetothermal treatment. The results are analyzed as follows: Figure 11 and Figure 12 As shown, the stenosis rate in the control group was approximately 50%, while it was only 25% in the magnetothermal group. Compared with the control group, the degree of luminal stenosis in the magnetothermal group was reduced by about 50%, indicating that magnetothermal therapy can effectively inhibit the occurrence of ISR. Furthermore, compared with the control group, the optical density of vimentin, CD68, and α-SMA in the vascular wall of the magnetothermal group decreased by 41.5%, 46.6%, and 46.7%, respectively, indicating that MSH thermotherapy simultaneously has both "anti-proliferative" and "anti-inflammatory" effects, helping to achieve better vascular repair quality while reducing the maintenance of restenosis. Blood biochemistry results showed no significant difference (ns) in serum TC, TG, and lipoprotein cholesterol (LDL-C and HDLC) concentrations between the magnetothermal group and the control group. Figure 13 As shown. This indicates that hyperthermia has little effect on systemic lipid metabolism / has good safety, and the possibility of restenosis differences due to differences in blood lipids can be ruled out.

[0055] The embodiments of the present invention have been described in detail above. Specific examples have been used to illustrate the principles and implementation methods of the present invention. The description of the above embodiments is only for the purpose of helping to understand the method and core ideas of the present invention. At the same time, for those skilled in the art, there will be changes in the specific implementation methods and application scope based on the ideas of the present invention. Therefore, the content of this specification should not be construed as a limitation of the present invention.

Claims

1. A self-temperature-controlled magnetothermal stent, wherein the self-temperature-controlled magnetothermal stent is used to inhibit restenosis after PCI, characterized in that, The magnetocaloric support is a tubular mesh structure, consisting of multiple unit rings connected sequentially along the axial direction. Adjacent unit rings are staggered in the circumferential direction and connected by connecting sections. The magnetocaloric support uses a ternary alloy system based on Fe-Ni-Cr as the main material of the magnetic support, with the following mass percentages: Fe 44.22%~45.06%, Ni 44.94%~45.78%, and Cr 10%.

2. The magnetothermal support according to claim 1, characterized in that, The unit ring is a periodic waveform structure. The unit ring is formed by multiple repeating units connected end to end to form a closed loop. Each repeating unit contains at least one peak and one valley. The connection between adjacent peaks and valleys forms a turning point. Multiple repeating units form a rhomboid grid unit, so that the support forms a closed loop skeleton.

3. The magnetothermal support according to claim 2, characterized in that, Adjacent unit rings are connected by connecting segments, which are connected to the turning points.

4. The magnetothermal support according to claim 3, characterized in that, The magnetothermal support is composed of support wires with a width of th. The unit rings have different ring heights in different axial regions. The ring height of the proximal unit ring is hs1, and the ring height of the distal unit ring is hs2. The hs1 ring height unit ring and the hs2 ring height unit ring account for 3 / 8 and 5 / 8 of the total number of unit rings, respectively, and the ring height hs1 > hs2.

5. The magnetothermal support according to claim 4, characterized in that, The dimensions of the magnetothermal support include: an outer diameter of 2-6 mm, a thickness of 0.05-0.2 mm, a length of 12-14.5 mm, a support wire width of th of 0.07 mm-0.20 mm, ring heights hs1 and hs2 of 1.20 mm-2.25 mm, and a ring density Ns of 6-13; the ring density Ns is the number of repeating units in the circumferential direction.

6. The magnetothermal support according to claim 5, characterized in that, The magnetothermal stent can be radially deployed via balloon expansion or an equivalent method.

7. A method for preparing a self-temperature-controlled magnetocaloric support as described in any one of claims 1-6, characterized in that, The preparation method includes the following steps: S1) Determine the Curie temperature range of the magnetic stent: Determine the thermotherapy temperature window; Based on the thermotherapy temperature window, and considering the temperature gradient caused by uneven blood flow cooling, derive and determine the required Curie temperature range for the magnetic stent material. S2) Screening of alloy systems for synergistic biomedical and magnetocaloric functions: Based on the Curie temperature range described in S1, a ternary alloy system based on Fe-Ni-Cr was selected as the main material for the magnetic scaffold. S3) Material composition ratio: Based on the CALPHAD method of multi-element phase diagram calculation, the phase stability, order-disorder transition and magnetic phase transition temperature of the ternary alloy system described in S2 are calculated in high throughput. Combined with experimental verification, the composition ratio of the material components of the ternary alloy system is determined. S4) Support structure design: The magnetothermal support is a tubular mesh structure, and multiple unit rings connected in sequence along the axial direction constitute the tubular mesh structure. Adjacent unit rings are staggered in the circumferential direction and connected by connecting segments. S5) Manufacturing of the magnetothermal support: The materials in the composition ratio described in S3 are sequentially melted into metal, cast into shape, hot-working and heat-treated after casting, and then drawn to obtain a metal capillary. The magnetothermal support described in S4 is then obtained by femtosecond laser etching and polished.

8. The preparation method according to claim 7, characterized in that, The thermotherapy temperature window described in S1 is 43~46℃.

9. The preparation method according to claim 8, characterized in that, The magnetic thermal stent-assisted control method includes: a safety monitoring and emergency termination mechanism: a dual safety guarantee is set up, relying on the self-temperature control characteristics of the magnetic thermal stent, and an infrared thermal imager is simultaneously activated to perform real-time imaging of the temperature of the target blood vessel area; the AMF generator is interlocked with the electrocardiogram monitoring system; and an emergency stop button is set up to terminate the hyperthermia.

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