WO2017100977A1

WO2017100977A1 - Individualized polymer stent and manufacturing method therefor and use thereof

Info

Publication number: WO2017100977A1
Application number: PCT/CN2015/097260
Authority: WO
Inventors: 赵庆洪; 石桂欣; 刘青; 赵清华; 崔淑君
Original assignee: 北京阿迈特医疗器械有限公司
Priority date: 2015-12-14
Filing date: 2015-12-14
Publication date: 2017-06-22
Also published as: CN108025108B; CN108025108A

Abstract

An individualized polymer stent and a manufacturing method and use thereof. The stent has a shape and size matching the shape and size of an inner cavity or a cavity outer profile of a part where the stent is to be used, and has a stent structure formed by deposition of polymer filaments according to a predesigned pattern, and the stent has at least one variable diameter along the length direction of the stent. Manufacture, according to the data of the inner cavity or the cavity outer profile scanned by the medical image of the part where the stent is to be used, a hollow or solid individualized stent mold matching the shape and size of the inner cavity or the cavity outer profile of the part where the stent is to be used; and sleeve the mold on a fourth shaft of a four-shaft rapid prototyping system or directly use the mold as the fourth shaft in order for receiving the polymer, so as to manufacture the individualized stent product. The shape and size of the stent match the part where the stent is to be used, the length, angle and curvature of the stent are more adapted to the construction form of the part where the stent is to be used, being able to meet the special requirements of the part where the stent is to be used, so that the wall adhering performance and the treatment effect of the stent is improved.

Description

Personalized polymer stent and preparation method and use thereof

Technical field

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.

Background technique

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). 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.

At present, in interventional medicine, 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. .

However, the types of stents currently sold at home and abroad have been standardized or standardized, and the size difference requirements of the patient's lesions have not been considered. For example, 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. Usually 3.5, 4.0, 4.5mm, 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.

Although 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. Injury, causing subsequent immune responses, such as excessive migration of smooth muscle Proliferation, intimal hyperplasia caused restenosis; at the same time, poor adherence will also cause blood cells to adhere to the surface of the stent, easily forming a stent thrombus.

In order to better solve the stenosis of blood vessels, a conical blood vessel stent has appeared on the domestic and international markets.

And RX

(Abbott, 2mm taper, length 30, 40mm, suitable for carotid diameter of 4 ~ 9mm),

RX (Medtronic, 2 & 3mm taper, length 30 & 40mm, suitable for carotid diameter of 4 ~ 9mm),

(Medtronic, 4mm taper, length 150mm, suitable for 22 to 46mm thoracic aortic diameter), HerculesTM (minimally invasive medical treatment: 4&6mm taper for thoracic aorta; 2mm taper for radial artery), variable diameter vascular stent Related patents are also being disclosed, WO 98/53759 (YADAV et al.) discloses a reduced-diameter carotid stent, US 2001/0010013 A1 (Daniel L et al.) discloses a self-expanding conical stent, WO 02/13727 A1 (LifeSciences) discloses a trumpet-shaped carotid stent, CN 201135516Y (Lepu Medical) discloses a metal or alloy variable diameter vascular stent, CN 203425071 U (Jiangsu University) discloses a metal or alloy For stents with conical vessels, CN 203388973 U (Zhou Yujie) discloses a conical metal stent, CN 202875544 U (Liaoning Biomedical Materials Research and Development Center Co., Ltd.) discloses a variable diameter stent adapted to the physiological characteristics of pulmonary arteries. . 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. The observation of blood pressure changes after carotid sinus conical stenting (Chongqing Medical, June 2009, Vol. 38, No. 11, 1299-1300.) and other domestic and international clinical studies have also proved that the variable diameter stent is straighter than The stent has a lower stent implantation complication.

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. Currently, 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.

At the same time, 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. Currently, the materials and manufacturing methods of stents and vascular stents are basically the same. Related patents, for example, 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, and 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.

In summary, 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.

The application of non-vascular stent products is 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. .

The development of clinical imaging medicine, such as angiography and optical coherence tomography (OCT), makes it possible to obtain 3D size information of the patient's lesion before surgery.

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, and 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. However, 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.

Summary of the invention

Accordingly, it is an object of 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.

To help understand the invention, some terms are defined below. The terms defined herein have the meaning commonly understood by one of ordinary skill in the art to which the invention pertains.

Unless otherwise stated, the term "solid or hollow personalized stent mold" as used herein 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. When it is desired to fit over the fourth shaft, 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.

The term "zigzag and/or woven structure" as used herein, unless otherwise indicated, refers to a form of stent structure formed using a "Z" shaped wire routing and/or a "latitude and longitude" braided wire routing.

The term "arc-shaped structure" as used herein, unless otherwise indicated, refers to the internal structure of the stent formed by a "smooth" curved wire routing.

Unless otherwise stated, the term "arc double-chamfer structure" as used herein 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.

The term "woven and bridge structure" as used herein, unless otherwise indicated, 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 object of the present invention is achieved by the following technical solutions:

In one aspect, 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 A stent structure constructed by depositing, wherein the stent has at least one varying diameter along the length of the stent.

Preferably, 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.

Preferably, 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.

Preferably, 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.

Preferably, 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.

Preferably, 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.

Preferably, 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.

In another aspect, 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:

(i) a pedestal;

(ii) a three-axis X-Y-Z positioning system coupled to the base, wherein the X-Y-Z positioning system defines X, Y, and Z directions, respectively;

(iii) a dispensing system mounted on the X-Y-Z positioning system and moving by the X-Y-Z positioning system, the dispensing system containing a nozzle;

(iv) 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;

(v) a computer control system that can accurately control the XYZ positioning system according to a set program to accurately control the movement of the nozzles of the distribution system in the X, Y, Z directions, and precisely control the rotation lever of the fourth axis system Rotation around the axis;

The method includes the following steps:

1) preparing a solid or hollow personalized stent mold matching the shape and size of the lumen or cavity contour of the portion to be used, according to the structural data of the lumen or the contour of the cavity to be used;

2) according to the personalized stent mold, using a computer to edit the program to set the shape, size and structure of the bracket;

3) According to the set shape, size and bracket structure, the bracket processing program is generated by automatic or manual method;

4) Set the operating parameters of the distribution system;

5) fixing the personalized bracket mold to the position of the rotating rod of the fourth axis system of the four-axis rapid prototyping system so that it can be forwarded with the fourth axis rotating rod under the control of the computer control system or Reverse rotation; and the polymer is added to the distribution system of the four-axis rapid prototyping system;

6) Control the XYZ positioning system and the fourth axis system by a computer control system, so that the dispensing system accurately extrudes the polymer filaments according to the set stent structure pattern, and deposits the specificity of the personalized stent mold that can be rotated on the fourth axis. The position to create a personalized stent of a particular shape, size and configuration.

Preferably, 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.

Preferably, the method further comprises the step of removing the fabricated stent from the fourth shaft.

Preferably, 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.

Preferably, in step 5), 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 dispensing system in the X, Y, Z directions, and to precisely control the rotation of the rotating shaft of the fourth shaft system about its axis.

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. At the position of the rotating rod of the four-axis 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. According to the mold model and the desired bracket structure editing program, 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. In a preferred embodiment, 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. For example, when the polymer melt is transported in a molten state, it can adhere well to other materials and maintain a certain shape, and the thermal fuse can adhere to the pre-extrusion wire that meets it, thereby eliminating the glue. usage of. For each given polymer material, 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.

When the stent is prepared by the extrusion molding apparatus, 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. According to the structural design of the stent, different polymer materials are sequentially extruded on a rotating rod or a mold on a rotating rod.

Another aspect of the invention also provides for the external morphological design of the prepared personalized in vivo polymeric scaffold. 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.

In still another aspect, 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. The use of a stent, gastric stent, or intestinal stent.

In still another aspect, the present invention provides a method of treating a stenosis caused by a lesion in a subject, comprising:

(1) scanning the configuration of the lumen of the stenosis caused by the lesion, obtaining structural data of the lumen or extraluminal contour of the stenotic lumen;

(2) preparing a personalized stent by using the method for preparing a personalized polymer stent according to the present invention;

(3) placing the stent in a snug manner outside the lumen or lumen of the narrow lumen to support the narrow lumen.

Preferably, in the method of the present invention for treating a stenosis caused by a lesion in a subject, 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.

BRIEF DESCRIPTION OF THE DRAWINGS

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);

2 is a schematic plan view showing the planar structure of another radial artery stent prepared in the first embodiment of the present invention;

3 is a schematic plan view showing another radial artery stent prepared in the longitudinal direction of the first embodiment of the present invention;

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 best way to implement the invention

The invention is further described in detail below with reference to the following examples, which are not intended to limit the invention.

Example 1

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:

1) Collecting local lumen data of the radial artery, obtaining a 3D model of the arterial cavity after 3D reconstruction in vitro, and then preparing a hollow personalized stent mold matching the inner surface of the radial artery with 3D printing technology or traditional CNC machine tool processing technology;

2) Using a computer program to design the structure of the bracket, and combining the shape and size of the mold, synchronously design the XYZ routing program and the fourth axis rotation program;

3) Automatically or manually generate a bracket processing program according to the designed bracket structure, shape and size;

4) 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;

5) 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.

Example 2

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:

1) Collect the local contour data of the trachea, obtain the 3D model of the trachea after 3D reconstruction in vitro, and then use the 3D printing technology or the traditional CNC machine tool processing technology to prepare a solid personalized stent mold matching the outer contour of the trachea;

4) replacing the rotating rod of the fourth-axis system of the four-axis rapid prototyping system with the solid personalized stent mold to receive the polymer and enable it to be forwarded according to the designed rotation program under the control of the computer control system Or reverse rotation; the polylactic acid pellets are added into the dispensing system of the apparatus, and the dispensing system sequentially extrudes the filaments on the personalized stent mold rotating on the fourth axis according to the routing path set in the control system, thereby preparing Degradable polymer tracheal stent;

5) The extruded stent is removed from the personalized stent mold for subsequent processing.

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. .

Example 3

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:

1) Collecting the local lumen data of the esophagus and obtaining a 3D model of the esophagus after 3D reconstruction in vitro. Then, using 3D printing technology or traditional CNC machine tool processing technology, a hollow personalized stent mold matching the inner contour of the esophagus is prepared;

4) 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;

5) The extruded stent is removed from the personalized mold for subsequent processing.

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.

Claims

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 stent structure constructed from polymer filaments deposited in a pre-designed pattern. Wherein the stent has at least one varying diameter along the length of the stent.
The stent according to claim 1, wherein the stent has a regular or irregular shape, preferably selected from the group consisting of tapered cones, dumbbells, and irregular curved shapes.
The stent according to claim 1, wherein the polymer is a degradable polymer selected from one or more of the group consisting of polylactic acid (PLA), L-polylactic acid (PLLA), and right. Polylactic acid (PDLA), polyethylene glycol-polyglycolic acid (PGA), polycaprolactone (PCL), polyethylene glycol (PEG), polyanhydride, polyhydroxyalkanoate (PHA), polypair Dioxanone, polyiminocarbonate, polyfumaric acid, degradable polyurethane, copolymer or mixture of the above materials, and mixtures of one or more of the above materials with other polymer materials which are degradable.
The stent of claim 1 wherein said polymer is a non-biodegradable polymer selected from one or more of the group consisting of polyesters such as polyethylene terephthalate. , polybutylene terephthalate; nylon, such as nylon 6, nylon 66; polyethylene, polytetrafluoroethylene, polypropylene, polyurethane, silicone rubber, and copolymers or mixtures of the above materials.
The stent according to any one of claims 1 to 4, wherein 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 duct stent, a gastric stent or an intestinal stent; preferably, the stent surface is sprayed with a drug that inhibits cell growth.
A method of preparing the stent of any one of claims 1 to 5, wherein the method is performed using a four-axis rapid prototyping system as a manufacturing apparatus, the four-axis rapid prototyping system comprising:

(i) a pedestal;

(ii) a three-axis X-Y-Z positioning system coupled to the base, wherein the X-Y-Z positioning system defines X, Y, and Z directions, respectively;

(iii) a dispensing system mounted on the X-Y-Z positioning system and moving by the X-Y-Z positioning system, the dispensing system containing a nozzle;

(iv) 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;

(v) a computer control system that can accurately control the XYZ positioning system according to a set program to accurately control the movement of the nozzles of the distribution system in the X, Y, Z directions, and precisely control the rotation lever of the fourth axis system Rotation around the axis;

The method includes the following steps:

1) preparing a solid or hollow personalized stent mold matching the shape and size of the lumen or cavity contour of the portion to be used, according to the structural data of the lumen or the contour of the cavity to be used;

2) according to the personalized stent mold, using a computer to edit the program to set the shape, size and structure of the bracket;

3) generating a bracket processing program according to the set shape, size and bracket structure of the bracket;

4) Set the operating parameters of the distribution system;

5) fixing the personalized bracket mold to the position of the rotating rod of the fourth axis system of the four-axis rapid prototyping system so that it can be forwarded with the fourth axis rotating rod under the control of the computer control system or Reverse rotation; and the polymer is added to the distribution system of the four-axis rapid prototyping system;

6) Control the XYZ positioning system and the fourth axis system by a computer control system, so that the dispensing system accurately extrudes the polymer filaments according to the set stent structure pattern, and deposits the specificity of the personalized stent mold that can be rotated on the fourth axis. The position to create a personalized stent of a particular shape, size and configuration.
The method according to claim 6, wherein said preparing in step 1) is carried out using a 3D printing technique or a numerically controlled machine tool processing method.
The method according to claim 6, wherein the fixing is performed using a jig in step 5) or by sleeving a hollow personalized stent mold on a rotating rod of the fourth shaft system.
The method of claim 6 wherein in step 5) the individualized stent mold is used in place of the rotating shaft of the fourth shaft system to receive the polymer, which is secured to the fourth shaft system and enabled to be in the computer Rotate in the forward or reverse direction under the control of the control system.
The use of the personalized polymer stent according to any one of claims 1 to 5 as a blood vessel stent or a body cavity stent, for example, as a cardio-cerebral stent, a peripheral vascular stent, a biliary stent, a urinary stent, a tracheal stent, an esophageal stent, Use of pancreatic duct stents, gastric stents, or intestinal stents.
A method of treating a stenosis caused by a lesion in a subject, comprising:

(1) scanning the configuration of the lumen of the stenosis caused by the lesion, obtaining structural data of the lumen or extraluminal contour of the stenotic lumen;

(2) preparing a personalized stent using the method of any one of claims 6 to 9;

(3) placing the stent in a snug manner outside the lumen or lumen of the narrow lumen to support the narrow lumen.