WO2017100977A1 - 一种个性化聚合物支架及其制备方法和用途 - Google Patents

一种个性化聚合物支架及其制备方法和用途 Download PDF

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Publication number
WO2017100977A1
WO2017100977A1 PCT/CN2015/097260 CN2015097260W WO2017100977A1 WO 2017100977 A1 WO2017100977 A1 WO 2017100977A1 CN 2015097260 W CN2015097260 W CN 2015097260W WO 2017100977 A1 WO2017100977 A1 WO 2017100977A1
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Prior art keywords
stent
axis
polymer
personalized
lumen
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PCT/CN2015/097260
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English (en)
French (fr)
Inventor
赵庆洪
石桂欣
刘青
赵清华
崔淑君
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北京阿迈特医疗器械有限公司
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Priority to PCT/CN2015/097260 priority Critical patent/WO2017100977A1/zh
Priority to CN201580083108.4A priority patent/CN108025108B/zh
Publication of WO2017100977A1 publication Critical patent/WO2017100977A1/zh

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    • A—HUMAN NECESSITIES
    • A61—MEDICAL OR VETERINARY SCIENCE; HYGIENE
    • A61F—FILTERS IMPLANTABLE INTO BLOOD VESSELS; PROSTHESES; DEVICES PROVIDING PATENCY TO, OR PREVENTING COLLAPSING OF, TUBULAR STRUCTURES OF THE BODY, e.g. STENTS; ORTHOPAEDIC, NURSING OR CONTRACEPTIVE DEVICES; FOMENTATION; TREATMENT OR PROTECTION OF EYES OR EARS; BANDAGES, DRESSINGS OR ABSORBENT PADS; FIRST-AID KITS
    • A61F2/00—Filters implantable into blood vessels; Prostheses, i.e. artificial substitutes or replacements for parts of the body; Appliances for connecting them with the body; Devices providing patency to, or preventing collapsing of, tubular structures of the body, e.g. stents
    • A—HUMAN NECESSITIES
    • A61—MEDICAL OR VETERINARY SCIENCE; HYGIENE
    • A61L—METHODS OR APPARATUS FOR STERILISING MATERIALS OR OBJECTS IN GENERAL; DISINFECTION, STERILISATION OR DEODORISATION OF AIR; CHEMICAL ASPECTS OF BANDAGES, DRESSINGS, ABSORBENT PADS OR SURGICAL ARTICLES; MATERIALS FOR BANDAGES, DRESSINGS, ABSORBENT PADS OR SURGICAL ARTICLES
    • A61L27/00—Materials for grafts or prostheses or for coating grafts or prostheses
    • A61L27/14—Macromolecular materials

Definitions

  • the invention belongs to the field of medical instruments, and in particular relates to a personalized polymer stent and a preparation method and use thereof.
  • the stent is a mesh tubular instrument that is placed in an organ having a luminal structure in the human body for treating intraluminal stenosis due to a lesion.
  • the stent can support the lumen and keep the lumen open. Some stents also have the effect of preventing restenosis of the lumen.
  • the stent is usually placed in the lesion by percutaneous puncture or through the original pipeline of the human body under the guidance of imaging equipment (such as angiography machine, fluoroscopy machine, CT, MR, B-ultrasound).
  • imaging equipment such as angiography machine, fluoroscopy machine, CT, MR, B-ultrasound.
  • the process is called Interventional stent medicine. Due to its minimal invasiveness and high efficiency, since the United States in 1964, Dotter has used coaxial catheter technology for angioplasty of patients, and has been rapidly developed and applied.
  • the sites that need to be implanted include: blood vessels, biliary tract, urinary tract, trachea, esophagus, pancreatic duct, stomach, intestine, etc., wherein the amount of blood vessels is the largest. Since these different parts to be used themselves have different shapes, lumen diameters, lesion lengths, etc., it is necessary to provide a variety of stents that can be better matched to the shape and size of the lumen or extraluminal contour of the site to be used. .
  • cardiovascular stents and peripheral vascular stents are almost straight-line tubular in shape.
  • Cardiovascular stents are usually 2.5, 3.0, and 4.0 mm in diameter. Common lengths are 13, 18, 23, 29, 33, and 38 mm.
  • the common length is 7, 10, 13, 16mm
  • the outer stent diameter is usually 5 ⁇ 10mm, 12 ⁇ 18mm, 24 ⁇ 42mm
  • the common length is 20 ⁇ 80mm, 60 ⁇ 100mm, 140 ⁇ 160mm, compared with the thickness of the human blood vessels and the length of the diseased blood vessels, the length of the stenosis varies from person to person, etc.
  • the stent model is relatively simple. The stent is fixed in size and cannot meet the needs of changes in the length and diameter of the lesion in clinical patients.
  • interventional stenting is currently the most effective treatment for vascular disease, intravascular restenosis and stent thrombosis after stent implantation limit the application of this technique.
  • the shape of the stent is one of the main causes of restenosis and thrombosis. It is clinically shown that the straight tubular stent will cause different stresses on the different conforming parts of the vessel wall during the expansion process after implantation, resulting in different degrees of tearing of the vessel wall.
  • the above-mentioned blood vessel stents are all made of medical metal or alloy material, and the processing methods generally adopt knitting, laser engraving, etching, micro-charge processing, electroforming and die-casting, etc.
  • laser engraving is often used, and the main defects of such stent systems are: Laser engraving method to prepare traditional straight cylindrical stent products, the process is long, the engraving pipe needs to be prepared first, and then 70-80% of the material is wasted by cutting; 2.
  • the variable diameter bracket is prepared by laser engraving, and the straight cylindrical shape is also required to be prepared first.
  • the tube, cutting, post-expansion balloon expansion or heat treatment on a conical mold, the process is more complicated; 3, laser engraving can not prepare irregular shape or more complex stent products, still can not meet the clinical pathology and physiology Need.
  • the interventional stent technique is in non-vascular body lumens, such as biliary tract, urethra, trachea, and food. Tubes, pancreatic ducts, stomach, intestines and other parts of the stenosis, opening drainage channels and occlusion abnormal pathways are also an effective treatment.
  • stents and vascular stents are basically the same.
  • CN 2424786 Y discloses a high-intensity biliary stent prepared using a wire material
  • CN 203852712 U discloses a single-female biliary stent of polyurethane or polyethylene material
  • CN 2220875 Y discloses a nickel-titanium wire preparation.
  • Urinary tract stent CN 101480506 A discloses a degradable tracheal stent prepared from polydioxanone or polyglycolide monofilament
  • CN 103607975 A discloses a nickel-titanium alloy laser-cut esophageal stent
  • CN 102202605 A discloses a scaffold for preventing pancreatic disorders, which is prepared using a high molecular polymer. None of these methods address the need for individualized stents for patients.
  • the current clinical vascular stent products are still standardized products.
  • the structure of the stent is mostly straight-line tubular, and some stents, such as the carotid artery stent, the radial artery stent, and the thoracic aorta stent have a tapered external form, but the diversity of the lesion vessel is still relatively simple. Therefore, it still cannot meet the individual needs of clinical patients.
  • non-vascular stent products are also becoming more and more extensive, but due to the high rate of restenosis caused by the permanent existence and single shape of traditional stents, there is an urgent need for a new type of personalized stent for the patient's lesion. .
  • Chinese invention patent application (application number: 201080002569.1) discloses a four-axis rapid prototyping system and a method for preparing a three-dimensional porous tubular stent
  • the Chinese invention patent application (CN 104274867 A) discloses a degradable polymer stent and rapid molding with four axes A method of preparing a polymeric stent.
  • the above patent application still does not solve the single defect of the external shape of the stent, and does not satisfactorily meet the special requirements of the site to be used.
  • the present invention has been further studied and developed in view of the above-mentioned drawbacks in the prior art, and a new personalized polymer stent has been obtained.
  • the present invention to provide a personalized polymeric stent.
  • the shape and size of the inner cavity or the outer contour of the stent to be used are more closely matched to meet the special requirements of the site to be used. At the same time, it can also solve the subsequent complications of the stent and improve the safety and effectiveness of the stent.
  • Another object of the invention is to provide a method of making the personalized polymeric stent.
  • Yet another object of the invention is to provide the use of the personalized polymeric stent.
  • solid or hollow personalized stent mold refers to a part that has an outer contour that matches the lumen or extraluminal contour of the patient's lesion, when the stent is fabricated using a four-axis rapid prototyping system.
  • the processing of the stent profile is achieved on the fourth axis or directly as the fourth axis for receiving the polymer.
  • the article has a particular hollow cavity shape.
  • the personalized stent mold is prepared based on the 3D size information of the patient's lesion. Personalized molds can be prepared by CNC machine tool processing, or individual molds can be prepared by 3D printing methods.
  • zigzag and/or woven structure refers to a form of stent structure formed using a "Z" shaped wire routing and/or a "latitude and longitude” braided wire routing.
  • arc-shaped structure refers to the internal structure of the stent formed by a “smooth” curved wire routing.
  • arc double-chamfer structure refers to a curve-traversing route with “peak-valley” similar to “sine and cosine", with a peak or valley separated by an average of two parts.
  • the peak or valley like a double chamfer, forms the internal structure of the scaffold with double arc chamfers.
  • woven and bridge structure refers to two filaments that are “parallel” between the filaments, similar to two adjacent “bridges” in the river, and the individual filaments are designed to be woven. Forming the internal structure of the bracket of the braided bridge.
  • the present invention provides a personalized polymeric stent having a shape and size that matches the shape and size of the lumen or cavity contour of the site to be used, and having a pre-designed pattern of polymer filaments
  • the site to be used is a blood vessel or a body cavity, such as cardiovascular and cerebrovascular, peripheral blood vessels, biliary tract, urinary tract, trachea, esophagus, pancreatic duct, stomach, intestine, and the like.
  • a blood vessel or a body cavity such as cardiovascular and cerebrovascular, peripheral blood vessels, biliary tract, urinary tract, trachea, esophagus, pancreatic duct, stomach, intestine, and the like.
  • the shape of the bracket is a regular or irregular shape, including but not limited to a tapered cone, a dumbbell shape, an irregular curved shape, and the like.
  • the bracket structure is a zigzag and/or a braided structure, a circular arc structure, a circular double chamfered structure, and/or a braided and bridged structure.
  • the polymer is a degradable polymer, wherein the degradable polymer is selected from one or more of the following: polylactic acid (PLA), L-polylactic acid (PLLA), right-handed polylactic acid (PDLA), polyethylene glycol-polyglycolic acid (PGA), polycaprolactone (PCL), polyethylene glycol (PEG), polyanhydride, polyhydroxyalkanoate (PHA), polydioxane Hexone, polyiminocarbonate, polyfumaric acid, degradable polyurethane, copolymer or mixture of the above materials, and mixtures of one or more of the above materials with other polymeric materials that are degradable.
  • PLA polylactic acid
  • PLLA L-polylactic acid
  • PDLA right-handed polylactic acid
  • PGA polyethylene glycol-polyglycolic acid
  • PCL polycaprolactone
  • PEG polyethylene glycol
  • PEG polyanhydride
  • PHA polyhydroxyalkanoate
  • PHA poly
  • the polymer is a non-biodegradable polymer, wherein the non-biodegradable polymer is selected from one or more of the following: polyester, including but not limited to, polyethylene terephthalate, poly Butylene terephthalate; nylon, including but not limited to, nylon 6, nylon 66; polyethylene, polytetrafluoroethylene, polypropylene, polyurethane, silicone rubber, and copolymers or mixtures of the foregoing.
  • polyester including but not limited to, polyethylene terephthalate, poly Butylene terephthalate
  • nylon including but not limited to, nylon 6, nylon 66
  • the stent is a vascular stent or a body lumen stent, such as a cardiovascular vascular stent, a peripheral vascular stent, a biliary stent, a urinary stent, a tracheal stent, an esophageal stent, a pancreatic stent, a gastric stent, or an intestinal stent; preferably,
  • the stent surface is sprayed with a drug that inhibits cell growth.
  • the present invention provides a method of preparing a stent of the present invention, wherein the method is carried out using a four-axis rapid prototyping system as a manufacturing apparatus, the four-axis rapid prototyping system comprising:
  • a fourth shaft system coupled to the base, comprising a rotating rod coupled to the base below the nozzle, wherein the rotating rod is rotatable about a central axis thereof in a forward or reverse direction;
  • the central axis of the rotating rod is parallel to the Y axis;
  • the method includes the following steps:
  • the bracket processing program is generated by automatic or manual method
  • the preparation of the personalized stent mold in step 1) is based on a medical imaging technique (such as CT, MRI, angiography data or OCT data) of the lesion site of the patient, and a 3D model of the patient's lesion is obtained after 3D reconstruction in vitro. Then, it is prepared by 3D printing technology or CNC machine tool processing method.
  • a medical imaging technique such as CT, MRI, angiography data or OCT data
  • the method further comprises the step of removing the fabricated stent from the fourth shaft.
  • the fixing is carried out using a clamp in step 5) or by sleeving a hollow individualized stent mold onto a rotating rod of the fourth shaft system.
  • the personalized support bracket mold is used to replace the rotary shaft of the fourth shaft system to receive the polymer, fix it on the fourth shaft system, and enable it to be positive under the control of the computer control system. Rotate in the opposite direction.
  • the four-axis rapid prototyping system disclosed in the Chinese Patent Application No. 201080002569.1, which is incorporated herein by reference.
  • the four-axis rapid prototyping system includes: (i) a susceptor; (ii) a three-axis XYZ positioning system coupled to the pedestal, wherein the XYZ positioning system defines X, Y, and Z directions, respectively; (iii) mounting a distribution system on the XYZ positioning system and moving by the XYZ positioning system, the dispensing system comprising a nozzle; (iv) a fourth shaft system coupled to the base, included under the nozzle a rotating rod coupled to the base, wherein the rotating rod is rotatable about a central axis thereof in a forward or reverse direction; a center axis of the rotating rod is parallel to the Y axis; and (v) a computer control system, which may
  • the XYZ positioning system is precisely controlled according to a set program to precisely control the movement of the nozzles of
  • the invention adopts a new personalized stent processing technology and provides a method for individually producing a stent in vivo.
  • the preparation of the stent requires a personalized stent model to achieve a personalized stent external morphology.
  • the stent model can be obtained by scanning the structure of the site to be used by 3D medical imaging technology, and the 3D model of the site to be used is obtained after 3D reconstruction in vitro, and then 3D printing method or number
  • a conventional technique such as a controlled machine tool manufacturing method prepares a solid or hollow personalized stent mold that matches the shape and size of the lumen or cavity contour of the portion to be used, and fixes it to the four-axis rapid prototyping system.
  • the individualized stent mould is fixed directly to the rotating rod of the fourth shaft system, for example by means of a clamp or by placing a hollow individualized stent mould on the rotating shaft of the fourth shaft system
  • Fixing, or the personalized support bracket mold can be used instead of the rotary shaft of the fourth axle system to receive the polymer, fix it on the fourth axle system, and enable it to be positive under the control of the computer control system Or turn in the opposite direction.
  • the computer is input, and the X, Y, Z axis and the rotating rod are synchronously controlled by the computer control system, and the reasonable X, Y and Z are designed according to the ideal structure of the bracket.
  • the shaft routing path after the material is fed into the dispensing system of the extrusion equipment, the material distribution system accurately extrudes the filaments according to the set pattern and deposits them on a specific position on the individual mold, thereby A bracket of the required shape, size and structure.
  • the four-axis rapid prototyping system employed in the present invention can include a material extrusion or conveying apparatus and a set of operating systems for controlling material delivery conditions. More specifically, the forming system can include a feed system and an extrusion system, a four-axis positioning system, and a temperature control system.
  • the material delivery system is a polymeric melt extrusion system that directly extrudes the thermal fuse of the polymeric material.
  • the four-axis positioning system refers to a space controlled by a computer X, Y, Z axis and a rotating fourth axis rotating rod, which is driven by a stepping motor or a servo motor, which can be accurately rotated at a certain speed according to needs. Stop, rotate forward or backward.
  • the rotating rod can be equipped with a heater or operated in a temperature-controlled environment to control the softness and viscosity of the material being received to maximize the material's performance.
  • a heater or operated in a temperature-controlled environment to control the softness and viscosity of the material being received to maximize the material's performance.
  • the thermal fuse can adhere to the pre-extrusion wire that meets it, thereby eliminating the glue. usage of.
  • an ideal combination of parameters is needed to ensure adequate adhesion between the emerging polymer extrudates.
  • the set of parameters includes extrusion rate, material extrusion system moving rate, and melting chamber temperature.
  • the XYZ axis and the rotating rod are simultaneously controlled by a program edited by the computer control system, thereby simultaneously preparing a bracket for setting the internal structure and the external shape.
  • the system is also suitable for preparing a polymer stent of a hybrid material.
  • different polymer materials are sequentially extruded on a rotating rod or a mold on a rotating rod.
  • the stent body profile has at least one varying diameter along the length, including but It is not limited to shapes such as tapered cones, dumbbells, and irregular surfaces.
  • the present invention provides the use of the personalized polymer stent as a vascular stent or a body cavity stent, such as a cardio-cerebral stent, a peripheral vascular stent, a biliary stent, a urinary stent, a tracheal stent, an esophageal stent, and a pancreatic duct.
  • a vascular stent or a body cavity stent such as a cardio-cerebral stent, a peripheral vascular stent, a biliary stent, a urinary stent, a tracheal stent, an esophageal stent, and a pancreatic duct.
  • a stent, gastric stent, or intestinal stent such as a vascular stent or a body cavity stent.
  • the present invention provides a method of treating a stenosis caused by a lesion in a subject, comprising:
  • the subject is a human or an animal.
  • the invention provides a more diverse variety of stents, and the specialized stent products for different physiological and pathological parts of the patient are prepared by using the rapid prototyping system and the polymer material by specially designing the parts to be used, so that the parts to be used are most matched.
  • the bracket, the length, angle and curvature of the bracket are more adapted to the configuration of the part to be used, and can meet the special requirements of the part to be used, and the adhering performance and the therapeutic effect can be improved.
  • the biodegradable material is used to prepare the stent, and the stent gradually disappears after the healing site is used, and no subsequent complications are generated; the biodegradable stent is prepared by the stent rapid prototyping system, and the material, the external shape of the stent, and the internal structure of the stent can be formed in one step.
  • the procedure is quick and easy, and improves the fit of the stent to the lesion.
  • the personalized polymer stent provided by the invention can meet the requirements of transportability, support and compliance.
  • the invention realizes the personalized bracket design and preparation method, improves the adaptability of the stent to be used, and solves the problem that the traditional bracket has poor passing ability for distorting the to-be-used part; and the method is simple in operation, easy to control, and program change It is convenient and fast, and it is easier to produce the ideal bracket, which has wider application range. It also provides a new technical research direction for the personalized design of the bracket.
  • FIG. 1 is a schematic plan view showing a planar structure of a radial artery stent prepared in the longitudinal direction of the stent (ie, the longitudinal direction of the stent);
  • FIG. 2 is a schematic plan view showing the planar structure of another radial artery stent prepared in the first embodiment of the present invention
  • FIG. 3 is a schematic plan view showing another radial artery stent prepared in the longitudinal direction of the first embodiment of the present invention
  • FIG. 4 is a schematic plan view showing a planar structure of an extratracheal stent prepared in the longitudinal direction according to Embodiment 2 of the present invention
  • FIG. 5 is a schematic plan view showing the planar structure of another tracheal outer stent prepared in the second embodiment of the present invention.
  • Figure 6 is a perspective view of the tracheal outer bracket shown in Figure 4.
  • Figure 7 is a perspective view of the tracheal outer stent shown in Figure 5;
  • Figure 8 is a view showing the internal structure of an esophageal stent prepared in Example 3 of the present invention.
  • Figure 9 shows a perspective side view of the esophageal stent shown in Figure 8.
  • the degradable polymer stent suitable for the radial artery uses polylactic acid as the raw material and adopts the same zigzag processing route.
  • the specific processing steps are as follows:
  • the hollow personalized stent mold is placed on the rotating rod of the fourth axis system of the four-axis rapid prototyping system, and is fixed so that it can be rotated with the fourth axis rotating rod under the control of the computer control system. Rotating in the opposite direction; adding the polylactic acid pellets to the dispensing system of the apparatus, the dispensing system sequentially extruding the individual filaments of the filaments on the fourth axis according to the routing path set in the control system, thereby Preparing the radial artery degradable polymer scaffold;
  • the extruded stent is removed from the personalized mold and used for subsequent operations, such as pressing onto the balloon.
  • the schematic diagrams of the three radial artery stents are shown in Figure 1, Figure 2 and Figure 3.
  • the body is composed of a connected mesh ring unit and a connecting unit, and the outer shape is tapered in the longitudinal direction.
  • the diameter of the mesh along the axial direction may be the same or different, and the density of the mesh ring along the axial direction is the same, in the radial direction.
  • the density of the supporting unit is also the same, and the prepared bracket has a uniform radial supporting force under the condition of the variable diameter.
  • Degradable polymer stent for tracheal lumen formation using polylactic acid as raw material, adopts "back" shape processing route, the specific processing steps are as follows:
  • the two tracheal stents prepared in the longitudinal direction are shown in Fig. 4 and Fig. 5.
  • the main body is composed of a connected "back" unit.
  • the diameter of the filaments in the "back” unit can be the same or different.
  • the filament density may be the same or different, and the blank portion of the "back" shaped unit may be sized to realize a tracheal stent having different radial supporting forces; the corresponding three-dimensional structures are respectively shown in FIG. 6 and FIG.
  • the shape structure when used, is buckled from the outside of the trachea to the trachea, and the stent is sutured on the trachea through surgical sutures.
  • the preparation material has a certain elasticity, so the inner diameter of the "C" shape is variable, and the flexibility of the stent is improved. .
  • Degradable polymer stent for esophageal stenosis using polylactic acid as a raw material, using a braided processing route, the specific processing steps are as follows:
  • the hollow personalized stent mold is placed on the rotating rod of the fourth axis system of the four-axis rapid prototyping system, and is fixed so that it can be rotated with the fourth axis rotating rod under the control of the computer control system. Rotating in the opposite direction; adding the polylactic acid pellets to the dispensing system of the apparatus, the dispensing system sequentially extruding the individual filaments of the filaments on the fourth axis according to the routing path set in the control system, thereby Preparing the degradable polymer esophageal stent;
  • the internal structure of the prepared esophageal stent is shown in Fig. 8.
  • the main body is composed of a connected diamond-shaped unit.
  • the overall figure is shown in Fig. 9.
  • the diamond-shaped unit design and the curved contour can make the stent produce a gentle and gentle radial expansion. Obeying the peristalsis of the esophagus, thereby keeping the esophagus unobstructed and reducing the patient's foreign body sensation.
  • One end of the stent is conical and the other end is a cup-shaped design, which avoids the cutting effect of the stent on the esophageal mucosa.
  • the inner wall of the esophagus is damaged or even bleeding. Therefore, the stent prepared by the design has good adhesion to the esophageal wall and improves the stent implantation effect.

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Abstract

一种个性化聚合物支架及其制法和用途。支架具有与待使用部位内腔或腔外轮廓的形状和尺寸相匹配外形和尺寸，并且具有由聚合物细丝按照预先设计的图案沉积而构成的支架结构，支架沿支架的长度方向具有至少一种变化的直径。根据待使用部位的医学影像扫描的内腔或腔外轮廓的数据制备出与待使用部位内腔或腔外轮廓的形状和尺寸相匹配的空心或实心的个性化支架模具；将模具套在四轴快速成型***的第四轴上或直接作为第四轴用于接收聚合物，制备出个性化的支架产品。支架的形状和尺寸与待使用部位相匹配，支架的长度、角度和曲率更加适应待使用部位的构造形式，能够满足待使用部位的特殊要求，支架的贴壁性能和治疗效果得以改善。

Description

一种个性化聚合物支架及其制备方法和用途 技术领域
本发明属于医疗器械领域，具体涉及一种个性化聚合物支架及其制备方法和用途。
背景技术
支架是一种网管状器械，被放置在人体具有管腔结构的器官内，用于治疗由于病变而导致的管腔内狭窄。支架可以起到支撑管腔，使管腔保持通畅的作用。一些支架还具有预防管腔再狭窄的作用。
支架通常以经皮穿刺，或经人体原有的管道的方式，在影像设备(如血管造影机、透视机、CT、MR、B超)的引导下被放置在病变部位，该过程即所谓的介入支架医学。由于其微创性和高效性，自1964年美国Dotter采用同轴导管技术为病人进行血管成形术以来，得到了迅速发展和应用。
目前，在介入医学中，需要植入支架的部位有：血管、胆道、尿路、气管、食管、胰腺管、胃、肠等，其中血管用量最大。由于这些不同的待使用部位本身具有不同的形状、管腔直径和病变长度等，因而需要针对待使用部位的内腔或腔外轮廓的形状和尺寸提供能与其更好地匹配的多样化的支架。
然而，目前国内外销售的支架型号已经标准化或规格化，并没有考虑到患者病变部位的尺寸差异需求。例如，心血管支架和外周血管支架形态上几乎均是直网管状，心血管支架直径通常为2.5、3.0、4.0mm，常用长度为13、18、23、29、33、38mm，脑血管支架直径通常为3.5、4.0、4.5mm，常用长度为7、10、13、16mm，外周支架直径通常为5～10mm、12～18mm、24～42mm，常用长度为20～80mm、60～100mm、140～160mm，相比于人体血管粗细不一以及病变血管的长度情况、狭窄长度因人而异等情况，支架型号显的比较单一。支架规格固定，不能满足临床患者病变部位长度和直径变化的需求。
虽然介入支架治疗是目前针对血管疾病最为有效的治疗手段，但支架植入后的血管内再狭窄、支架内血栓形成限制了这一技术的应用。其中支架外形是影响再狭窄、形成血栓的主要成因之一，临床显示直筒状血管支架在植入后扩张过程中对血管壁不同贴合部位会造成不同的应力，导致血管壁不同程度的撕裂损伤，从而引起后续免疫反应，比如平滑肌过度迁移 增殖，内膜增生致再狭窄；同时，不良的贴壁亦会使血细胞在支架表面粘附聚集，容易形成支架内血栓。
为了更好地解决血管的狭窄病变，国内外市场上出现了锥形血管支架，
Figure PCTCN2015097260-appb-000001
和RX
Figure PCTCN2015097260-appb-000002
(Abbott，2mm锥度，长度30、40mm，适用于4～9mm的颈动脉径)、
Figure PCTCN2015097260-appb-000003
RX(Medtronic，2&3mm锥度，长度30&40mm，适用于4～9mm的颈动脉径)、
Figure PCTCN2015097260-appb-000004
(Medtronic，4mm锥度，长度150mm，适用于22～46mm的胸主动脉径)、HerculesTM(微创医疗：4&6mm锥度，适用于胸主动脉；2mm锥度，适用于髂动脉)，变径血管支架的相关专利也逐渐公开，WO 98/53759(YADAV等人)公开了变径的颈动脉支架，US 2001/0010013 A1(Daniel L等人)公开了一种自膨的锥形支架，WO 02/13727 A1(LifeSciences)公开了一种喇叭形的颈动脉支架，CN 201135516Y(乐普医疗)公开了一种金属或合金的变径血管支架，CN 203425071 U(江苏大学)公开了一种金属或合金的适用于锥形血管的支架，CN 203388973 U(周玉杰)公开了一种锥形金属血管支架，CN 202875544 U(辽宁生物医学材料研发中心有限公司)公开了一种适应肺动脉血管生理特点的变径支架。Carotid stenting using tapered and nontapered stents:associated neurological complications and restenosis rates.(Ann Vasc Surg.2009 Jul-Aug；23(4):439-45.doi:10.1016/j.avsg.2008.11.007.Epub 2009 Jan 6.)、Radial force measurements in carotid stents:influence of stent design and length of the lesion.(J Vasc Interv Radiol.2011 May；22(5):661-6.doi:10.1016/j.jvir.2011.01.450.)、颈动脉窦部锥形支架成形术后血压变化的观察(重庆医学2009年6月第38卷第11期，1299-1300.)等国内外的临床研究也证明了变径支架比直型支架有更低的支架植入并发症。
上述血管支架均采用医用金属或合金材质，加工方法一般采用编织、激光雕刻、蚀刻、微电荷加工、电成型及模铸等，目前多采用激光雕刻，此类支架体系的主要缺陷为：1、激光雕刻法制备传统直筒状支架产品，过程较长，需要先制备雕刻管材，再经切割，70～80％的材料被浪费掉；2、激光雕刻法制备变径支架，同样需要先制备直筒状的管材，切割，后期用变径球囊膨胀或者在锥形模具上热处理，该过程更加复杂；3、激光雕刻无法制备不规则形状的或形状比较复杂的支架产品，仍然不能满足临床病理及生理的需要。
与此同时，介入支架技术在非血管体腔，比如胆道、尿道、气管、食 管、胰腺管、胃、肠等部位疏通狭窄、开通引流通道和闭塞异常通路等方面也是一种有效的治疗方法，目前临床上使用的支架与血管支架的材质和制造方法基本相同。相关专利如，CN 2424786 Y公开了一种采用金属丝材编制的高造影胆道支架，CN 203852712 U公开了一种聚氨酯或聚乙烯材料的单凤尾胆道支架，CN 2220875 Y公开了镍钛丝编制的尿道支架，CN 101480506 A公开了可降解的气管支架，由聚对二氧环己酮或聚乙交酯单丝编制而成，CN 103607975 A公开了一种镍钛合金激光切割成的食管支架，CN 102202605 A公开了一种预防胰腺病症的支架，采用高分子聚合物制备。这些方法都没有解决患者个体化支架的需求问题。
综上，目前临床上的血管支架产品仍然是规格化的产品。支架的结构多为直网管状，部分支架，如颈动脉支架、髂动脉支架、胸主动脉支架有锥形的外部形式，但相对于病变血管的多样化仍显的比较单一。因此仍然不能满足临床上患者的个性化需求。
非血管支架产品的应用也越来越广泛，但由于传统支架的永久存在性及形状单一性导致的再狭窄率高的现状，使得临床上迫切需要新型的针对患者的病变部位的个性化支架出现。
临床影像医学的发展，例如血管造影术，光学相干断层扫描技术(Optical Coherence Tomography，OCT)，使得术前获取患者病变部位的3D尺寸信息成为可能。
中国发明专利申请(申请号：201080002569.1)公开了一种四轴快速成型***及制备三维多孔管状支架的方法，中国发明专利申请(CN 104274867 A)公开了可降解聚合物支架以及用四轴快速成型***制备聚合物支架的方法。但是上述专利申请仍然没有解决支架外部形态单一的缺陷，不能很好地满足待使用部位的特殊要求。本发明针对上述现有技术中存在的缺陷，进行了进一步研究和开发，得到了一种新的个性化聚合物支架。
发明内容
因此，本发明的一个目的是提供一种个性化聚合物支架。所述支架与待使用部位的内腔或腔外轮廓的形状和尺寸更加匹配，能够满足待使用部位的特殊要求。同时，还能够解决支架的后续并发症问题，提高支架的安全性和有效性。
本发明的另一个目的是提供一种制备所述个性化聚合物支架的方法。
本发明的又一个目的是提供所述个性化聚合物支架的用途。
为有助于理解本发明，下面定义了一些术语。本文定义的术语具有本发明相关领域的普通技术人员通常理解的含义。
除非另外说明，本文所用的术语“实心或空心的个性化支架模具”是指外部轮廓与患者病变部位内腔或腔外轮廓相匹配的制件，在采用四轴快速成型***制作支架时，套在第四轴上或者直接作为第四轴用于接收聚合物实现支架外形的加工。当需要套在第四轴上时，制件具有特定的空心内腔形状。个性化支架模具是根据患者病变部位的3D尺寸信息制备的。可以采用数控机床加工方式制备个性化模具，也可以采用3D打印方法等制备个性化模具。
除非另外说明，本文所用的术语“Z字形和/或编织形结构”是指采用“Z”字形走丝路线和/或“经纬”编织形走丝路线形成的支架结构形式。
除非另外说明，本文所用的术语“圆弧形结构”是指采用“圆滑”的曲线走丝路线形成的支架内部结构。
除非另外说明，本文所用的术语“圆弧双倒角结构”是指类似“正弦、余弦”的具有“峰-谷”的曲线走丝路线，而相隔一个峰或谷又被平均分成两部分的峰或谷，类似一种双倒角，形成圆弧双倒角的支架内部结构。
除非另外说明，本文所用的术语“编织并桥结构”是指丝与丝之间采用“平行”的两条丝，类似河流中两座毗邻的“桥”，而独立的丝被设计成编织结构，形成编织并桥的支架内部结构。
本发明的目的是通过以下技术方案来实现的：
一方面，本发明提供一种个性化聚合物支架，其具有与待使用部位的内腔或腔外轮廓的形状和尺寸相匹配的外形和尺寸，并且具有由聚合物细丝按照预先设计的图案沉积而构成的支架结构，其中，所述支架沿支架的长度方向具有至少一种变化的直径。
优选地，所述待使用部位为血管或体腔，例如心脑血管、外周血管、胆道、尿路、气管、食管、胰腺管、胃、肠等。
优选地，所述支架的外形为规则或不规则形状，包括但不限于渐细的锥形、哑铃形、不规则曲面形状等。
优选地，所述支架结构为Z字形和/或编织形结构、圆弧形结构、圆弧双倒角结构、和/或编织并桥结构。
优选地，所述聚合物是可降解聚合物，其中所述可降解聚合物选自以下的一种或多种：聚乳酸(PLA)、左旋聚乳酸(PLLA)、右旋聚乳酸 (PDLA)、聚乙二醇-聚羟基乙酸(PGA)、聚己酸内酯(PCL)、聚乙二醇(PEG)、聚酸酐、聚羟基脂肪酸酯(PHA)、聚对二氧环己酮、聚亚氨基碳酸酯、聚富马酸，可降解聚氨酯、上述材料的共聚物或混合物，以及上述材料中的一种或多种与可降解的其它高分子材料的混合物。
优选地，所述聚合物是非生物降解聚合物，其中所述非生物降解聚合物选自以下的一种或多种：聚酯，包括但不限于，聚对苯二甲酸乙二醇酯，聚对苯二甲酸丁二醇酯；尼龙，包括但不限于，尼龙6，尼龙66；聚乙烯，聚四氟乙烯、聚丙烯，聚氨酯，硅橡胶，以及上述材料的共聚物或混合物。
优选地，所述支架为血管支架或体腔支架，如心脑血管支架、外周血管支架、胆道支架、尿路支架、气管支架、食管支架、胰腺管支架、胃支架、或肠支架；优选地，所述支架表面喷涂有抑制细胞生长的药物。
另一方面，本发明提供一种制备本发明所述的支架的方法，其中，所述方法使用四轴快速成型***作为制造设备来进行，所述四轴快速成型***包括：
(i)基座；
(ii)连接于所述基座的三轴X-Y-Z定位***，其中所述X-Y-Z定位***分别限定X、Y、Z方向；
(iii)安装在所述X-Y-Z定位***上，并通过所述X-Y-Z定位***移动的分配***，所述分配***含有一个喷嘴；
(iv)连接于所述基座的第四轴***，其包含在所述喷嘴下方连接于所述基座的旋转杆，其中，所述旋转杆可以围绕其中轴作正向或反向转动；所述旋转杆的中轴平行于Y轴；以及
(v)计算机控制***，其可以根据设定的程序精确地控制X-Y-Z定位***从而精确地控制分配***的喷嘴在X、Y、Z方向上的运动，并且精确地控制第四轴***的旋转杆围绕其中轴的转动；
所述方法包括以下步骤：
1)根据待使用部位的内腔或腔外轮廓的结构数据，制备出与待使用部位内腔或腔外轮廓的形状和尺寸相匹配的实心或空心的个性化支架模具；
2)根据所述个性化支架模具，采用计算机编辑设定支架外形、尺寸以及支架结构的程序；
3)根据设定的支架外形、尺寸以及支架结构，采用自动或手动的方法生成支架加工程序；
4)设定分配***运行参数；
5)将所述个性化支架模具固定到所述四轴快速成型***的第四轴***的旋转杆的位置处，使其能够在计算机控制***的控制下随第四轴旋转杆作正向或反向转动；并将聚合物加入四轴快速成型***的分配***内；
6)通过计算机控制***控制X-Y-Z定位***和第四轴***，使分配***精确地按照设定的支架结构图案挤出聚合物细丝，沉积在第四轴上可以旋转的个性化支架模具的特定位置，从而制备出所设计的具有特定外形、尺寸和结构的个性化支架。
优选地，步骤1)中所述个性化支架模具的制备是根据患者病变部位的医学成像技术(如CT,MRI,血管造影数据或OCT数据)，经体外3D重建后得到患者病变部位的3D模型，然后采用3D打印技术或者数控机床加工方法来制备的。
优选地，所述方法还包括将制得的支架从第四轴上取下的步骤。
优选地，步骤5)中使用夹具进行固定，或者通过将空心的个性化支架模具套在第四轴***的旋转杆上进行固定。
优选地，步骤5)中用所述个性化支架模具替代第四轴***的旋转杆来接收聚合物，将其固定在第四轴***上，并使其能够在计算机控制***的控制下作正向或反向转动。
制备本发明的个性化聚合物支架可采用一种四轴快速成型***，例如在申请号为201080002569.1的中国发明专利申请中所公开的四轴快速成型***。所述四轴快速成型***包括：(i)基座；(ii)连接于所述基座的三轴X-Y-Z定位***，其中所述X-Y-Z定位***分别限定X、Y、Z方向；(iii)安装在所述X-Y-Z定位***上，并通过所述X-Y-Z定位***移动的分配***，所述分配***含有一个喷嘴；(iv)连接于所述基座的第四轴***，其包含在所述喷嘴下方连接于所述基座的旋转杆，其中，所述旋转杆可以围绕其中轴作正向或反向转动；所述旋转杆的中轴平行于Y轴；以及(v)计算机控制***，其可以根据设定的程序精确地控制X-Y-Z定位***从而精确地控制分配***的喷嘴在X、Y、Z方向上的运动，并且精确地控制第四轴***的旋转杆围绕其中轴的转动。
本发明采用新的个性化支架加工工艺，提供了一种个性化生产体内支架的方法。制备所述支架需要个性化的支架模型以实现个性化的支架外部形态，支架模型可通过3D医学成像技术扫描待使用部位的构造得到，经体外3D重建后得到待使用部位的3D模型，然后采用3D打印方法或者数 控机床加工方法等传统技术制备出相应的与待使用部位内腔或腔外轮廓的形状和尺寸相匹配的实心或空心的个性化支架模具，将其固定到所述四轴快速成型***的第四轴***的旋转杆的位置处，例如通过夹具将所述个性化支架模具直接固定到第四轴***的旋转杆上或者通过将空心的个性化支架模具套在第四轴***的旋转杆上进行固定，或者也可以用所述个性化支架模具替代第四轴***的旋转杆来接收聚合物，将其固定在第四轴***上，并使其能够在计算机控制***的控制下作正向或反向转动。根据模具模型及期望的支架结构编辑程序之后输入计算机，通过计算机控制***达到对X、Y、Z轴和旋转杆的同步控制，依照所述支架的理想的结构设计出合理的X、Y和Z轴走线路径，将物料送入挤出设备的分配***内之后，使物料分配***精确地按照设定的图案挤出细丝，并沉积在个性化模具上特定的位置处，从而制成所需的形状、尺寸及结构的支架。
本发明所采用的四轴快速成型***可以包括一个物料挤出或输送设备以及一套控制物料输送条件的操作***。更具体地说，所述成型***可包含有一套进料***和挤出***，四轴定位***，温度控制***。在优选的实施例中，物料输送***是一个高分子熔融挤出***，可以直接挤出高分子材料的热熔丝。四轴定位***是指由计算机控制的空间X、Y、Z轴和旋转的第四轴旋转杆，该旋转杆由步进电机或伺服电机驱动，它可以精确地根据需要按一定的速度旋转，停止，向前或者向后旋转。旋转杆可以装备加热器或者在温控环境下操作，以便控制所接收物料的柔软度和黏性，从而发挥材料的最优性能。例如，高分子熔体在熔融状态下输送时可以跟其它材料有很好的粘附力并且保持一定形状，热熔丝能粘附到与它相遇的前期挤出丝上，因此可以省去胶水的使用。对于每一个给定的高分子材料，需要建立一套理想的组合参数来保证相遇的高分子挤出物之间有足够的粘附力。这套组合参数包括挤出速率、物料挤出***移动速率和熔融腔温度等。
采用所述挤出成型设备制备支架时，XYZ轴和旋转杆同时受计算机控制***编辑的一套程序控制，从而同步制备出设定内部结构和外部形态的支架。
所述***同样适用于制备混合型材料的高分子支架，根据支架的结构设计，依次将不同的高分子材料挤在旋转杆上或旋转杆上的模具上。
本发明另一方面还提供了对制备的个性化生物体内聚合物支架的外部形态设计。支架本体外形沿长度方向具有至少一种变化的直径，包括但 不限于渐细的锥形、哑铃型、不规则曲面等形状。
又一方面，本发明提供所述的个性化聚合物支架作为血管支架或体腔支架的用途，如作为心脑血管支架、外周血管支架、胆道支架、尿路支架、气管支架、食管支架、胰腺管支架、胃支架、或肠支架的用途。
还有一方面，本发明提供了一种治疗受试者因病变导致的管腔狭窄的方法，包括：
(1)扫描受试者因病变导致狭窄的管腔的构造，获得所述狭窄的管腔的内腔或腔外轮廓的结构数据；
(2)使用本发明所述的制备个性化聚合物支架的方法制备个性化支架；
(3)将所述支架以贴合的方式放置在所述狭窄的管腔的内腔或腔外以支撑所述狭窄的管腔。
优选地，在本发明治疗受试者因病变导致的管腔狭窄的方法中，所述受试者是人或动物体。
本发明提供了更加多样化的支架种类，通过针对待使用部位进行专门设计，利用快速成型***和聚合物材料制备出针对患者不同生理病理部位的个性化的支架产品，使得待使用部位得到最匹配的支架，支架的长度、角度和曲率更加适应待使用部位的构造形式，能够满足待使用部位的特殊要求，贴壁性能和治疗效果得以改善。采用生物可降解材料制备支架，待使用部位愈合后支架逐渐消失，不会产生后续并发症；通过支架快速成型***制备生物可降解支架，材料、支架外部形态、支架内部结构可以实现一步成型，制备过程方便快速，并且改进了支架与病变部位的贴合性能。本发明提供的个性化聚合物支架能够满足输送性、支撑性、顺应性的要求。
本发明实现了个性化的支架设计及制备方法，提升了支架对待使用部位的适应性，解决了传统支架对于迂曲待使用部位通过能力差的问题；且该方法操作简单，易于控制，同时程序更改方便快速，更易制出理想的支架，适用范围更广；也为支架的个性化设计提供了新的技术研究方向。
附图的简要说明
图1示出了本发明实施例1制备得到的一种髂动脉支架沿纵向(即支架的长度方向)展开的平面结构示意图；
图2示出了本发明实施例1制备得到的另一种髂动脉支架沿纵向展开的平面结构示意图；
图3示出了本发明实施例1制备得到的又一种髂动脉支架沿纵向展开的平面结构示意图；
图4示出了本发明实施例2制备得到的一种气管外支架沿纵向展开的平面结构示意图；
图5示出了本发明实施例2制备得到的另一种气管外支架沿纵向展开的平面结构示意图；
图6示出了图4所示的气管外支架立体图；
图7示出了图5所示的气管外支架立体图；
图8示出了本发明实施例3制备得到的一种食管支架内部结构图；
图9示出了图8所示的食管支架的立体侧视图。
实施发明的最佳方式
下面结合如下实施例对本发明做更进一步的详细说明，其并不意味着限制本发明。
实施例1
适用于髂动脉的可降解聚合物支架，用聚乳酸作为原材料，采用同向Z字形加工路线，具体加工步骤如下：
1)采集髂动脉局部内腔数据，经体外3D重建后得到动脉腔的3D模型，然后用3D打印技术或传统数控机床加工技术制备与髂动脉内腔面匹配的空心的个性化支架模具；
2)采用计算机程序设计支架的结构，并结合模具的外形、尺寸，同步设计XYZ走线程序以及第四轴旋转程序；
3)根据设计的支架结构和外形、尺寸，自动或手动生成支架加工程序；
4)将所述空心的个性化支架模具套在四轴快速成型***的第四轴***的旋转杆上，将其固定，使其能够在计算机控制***的控制下随第四轴旋转杆作正向或反向转动；将聚乳酸粒料加入设备的分配***内，分配***依据所述控制***中设定的走线路径依次挤出细丝在第四轴旋转的个性化支架模具上，从而制备出所述的髂动脉可降解聚合物支架；
5)将挤出的支架从个性化模具上取下后用于后续工序，如压握到球囊上的工序。
制备得到的三种髂动脉支架展开结构示意图如图1、图2、图3所示， 其本体是由连体的网环单元和连接单元构成，外形沿长度方向整体呈锥形，沿轴向的网丝直径可以相同，也可以不同，沿轴向网环密度相同，沿径向，支撑单元密度也相同，实现了制备的支架在变径的条件下，具有均匀的径向支撑力。
实施例2
用于气管管腔成型的可降解聚合物支架，用聚乳酸作为原材料，采用“回”字形加工路线，具体加工步骤如下：
1)采集气管局部腔外轮廓数据，经体外3D重建后得到气管的3D模型，然后用3D打印技术或传统数控机床加工技术制备与气管外部轮廓匹配的实心的个性化支架模具；
2)采用计算机程序设计支架的结构，并结合模具的外形、尺寸，同步设计XYZ走线程序以及第四轴旋转程序；
3)根据设计的支架结构和外形、尺寸，自动或手动生成支架加工程序；
4)用所述实心的个性化支架模具替代四轴快速成型***的第四轴***的旋转杆来接收聚合物，并使其能够在计算机控制***的控制下按照设计好的旋转程序作正向或反向转动；将聚乳酸粒料加入设备的分配***内，分配***依据所述控制***中设定的走线路径依次挤出细丝在第四轴旋转的个性化支架模具上，从而制备出所述的可降解聚合物气管支架；
5)将挤出的支架从个性化支架模具上取下后用于后续工序。
制备得到的两种气管支架沿纵向展开结构如图4、图5所示，其本体是由连体的“回”形单元构成，“回”形单元中的细丝直径可以相同，也可以不同，细丝密度可以相同，也可以不同，“回”形单元中空白部分尺寸可调，可以实现具有不同径向支撑力的气管支架；相应的立体结构分别如图6、图7所示“C”字形结构，使用时，从气管外部扣到气管上，通过手术缝合线将支架缝合在气管上，制备用原材料有一定的弹性，因此“C”字形内径可变，提高支架使用时的灵活性。
实施例3
用于食管狭窄的可降解聚合物支架，用聚乳酸作为原材料，采用编织形加工路线，具体加工步骤如下：
1)采集食管局部内腔数据，经体外3D重建后得到食管的3D模型， 然后用3D打印技术或传统数控机床加工技术制备与食管内部轮廓匹配的空心的个性化支架模具；
2)采用计算机程序设计支架的结构，并结合模具的外形、尺寸，同步设计XYZ走线程序以及第四轴旋转程序；
3)根据设计的支架结构和外形、尺寸，自动或手动生成支架加工程序；
4)将所述空心的个性化支架模具套在四轴快速成型***的第四轴***的旋转杆上，将其固定，使其能够在计算机控制***的控制下随第四轴旋转杆作正向或反向转动；将聚乳酸粒料加入设备的分配***内，分配***依据所述控制***中设定的走线路径依次挤出细丝在第四轴旋转的个性化支架模具上，从而制备出所述的可降解聚合物食管支架；
5)将挤出的支架从个性化模具上取下后用于后续工序。
制备得到的食管支架内部结构如图8所示，其本体是由连体的菱形单元构成，整体图如图9所示，菱形单元设计以及曲面轮廓能够使支架产生持续柔和的径向扩张，能顺从食道的蠕动，从而既保持食道通畅又降低了患者的异物感，支架的一端是圆锥形设计，另一端是杯口形设计，该种口部设计规避了由于支架对食道粘膜的切割效应而导致的食道内壁损伤甚至出血，因此该设计制备的支架与食管壁贴壁性良好，提高支架植入效果。

Claims (11)

  1. 一种个性化聚合物支架，其具有与待使用部位的内腔或腔外轮廓的形状和尺寸相匹配的外形和尺寸，并且具有由聚合物细丝按照预先设计的图案沉积而构成的支架结构，其中，所述支架沿支架的长度方向具有至少一种变化的直径。
  2. 根据权利要求1所述的支架，其中，所述支架的外形为规则或不规则形状，优选选自渐细的锥形、哑铃形和不规则曲面形状。
  3. 根据权利要求1所述的支架，其中所述聚合物是可降解聚合物，所述可降解聚合物选自以下的一种或多种：聚乳酸(PLA)、左旋聚乳酸(PLLA)、右旋聚乳酸(PDLA)、聚乙二醇-聚羟基乙酸(PGA)、聚己酸内酯(PCL)、聚乙二醇(PEG)、聚酸酐、聚羟基脂肪酸酯(PHA)、聚对二氧环己酮、聚亚氨基碳酸酯、聚富马酸、可降解聚氨酯，上述材料的共聚物或混合物，以及上述材料中的一种或多种与可降解的其它高分子材料的混合物。
  4. 根据权利要求1所述的支架，其中所述聚合物是非生物降解聚合物，所述非生物降解聚合物选自以下的一种或多种：聚酯，如聚对苯二甲酸乙二醇酯、聚对苯二甲酸丁二醇酯；尼龙，如尼龙6、尼龙66；聚乙烯，聚四氟乙烯，聚丙烯，聚氨酯，硅橡胶，以及上述材料的共聚物或混合物。
  5. 根据权利要求1至4中任一项所述的支架，其中，所述支架为血管支架或体腔支架，例如心脑血管支架、外周血管支架、胆道支架、尿路支架、气管支架、食管支架、胰腺管支架、胃支架或肠支架；优选地，所述支架表面喷涂有抑制细胞生长的药物。
  6. 一种制备权利要求1至5中任一项所述的支架的方法，其中，所述方法使用四轴快速成型***作为制造设备来进行，所述四轴快速成型***包括：
    (i)基座；
    (ii)连接于所述基座的三轴X-Y-Z定位***，其中所述X-Y-Z定位***分别限定X、Y、Z方向；
    (iii)安装在所述X-Y-Z定位***上，并通过所述X-Y-Z定位***移动的分配***，所述分配***含有一个喷嘴；
    (iv)连接于所述基座的第四轴***，其包含在所述喷嘴下方连接于所述基座的旋转杆，其中，所述旋转杆可以围绕其中轴作正向或反向转动； 所述旋转杆的中轴平行于Y轴；以及
    (v)计算机控制***，其可以根据设定的程序精确地控制X-Y-Z定位***从而精确地控制分配***的喷嘴在X、Y、Z方向上的运动，并且精确地控制第四轴***的旋转杆围绕其中轴的转动；
    所述方法包括以下步骤：
    1)根据待使用部位的内腔或腔外轮廓的结构数据，制备出与待使用部位内腔或腔外轮廓的形状和尺寸相匹配的实心或空心的个性化支架模具；
    2)根据所述个性化支架模具，采用计算机编辑设定支架外形、尺寸以及支架结构的程序；
    3)根据设定的支架外形、尺寸以及支架结构生成支架加工程序；
    4)设定分配***运行参数；
    5)将所述个性化支架模具固定到所述四轴快速成型***的第四轴***的旋转杆的位置处，使其能够在计算机控制***的控制下随第四轴旋转杆作正向或反向转动；并将聚合物加入四轴快速成型***的分配***内；
    6)通过计算机控制***控制X-Y-Z定位***和第四轴***，使分配***精确地按照设定的支架结构图案挤出聚合物细丝，沉积在第四轴上可以旋转的个性化支架模具的特定位置，从而制备出所设计的具有特定外形、尺寸和结构的个性化支架。
  7. 根据权利要求6所述的方法，其中，步骤1)中所述制备是采用3D打印技术或者数控机床加工方法来进行的。
  8. 根据权利要求6所述的方法，其中，步骤5)中使用夹具进行固定，或者通过将空心的个性化支架模具套在第四轴***的旋转杆上进行固定。
  9. 根据权利要求6所述的方法，其中步骤5)中用所述个性化支架模具替代第四轴***的旋转杆来接收聚合物，将其固定在第四轴***上，并使其能够在计算机控制***的控制下作正向或反向转动。
  10. 权利要求1至5中任一项所述的个性化聚合物支架作为血管支架或体腔支架的用途，例如作为心脑血管支架、外周血管支架、胆道支架、尿路支架、气管支架、食管支架、胰腺管支架、胃支架、或肠支架的用途。
  11. 一种治疗受试者因病变导致的管腔狭窄的方法，包括：
    (1)扫描受试者因病变导致狭窄的管腔的构造，获得所述狭窄的管腔的内腔或腔外轮廓的结构数据；
    (2)使用权利要求6至9中任一项所述的方法制备个性化支架；
    (3)将所述支架以贴合的方式放置在所述狭窄的管腔的内腔或腔外以支撑所述狭窄的管腔。
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CN110314024A (zh) * 2019-06-26 2019-10-11 北京工业大学 一种适形贴壁血管内支架
CN110314024B (zh) * 2019-06-26 2021-11-05 北京工业大学 一种适形贴壁血管内支架
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CN115317664A (zh) * 2022-06-09 2022-11-11 北京大学口腔医学院 哑铃型或米字型电活性钛支架增强复合膜及其制备方法
CN115464882A (zh) * 2022-10-09 2022-12-13 上海交通大学医学院附属新华医院 一种3d打印滑扣婴幼儿生物可吸收血管支架的制备方法

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