A multi-material bionic structure tracheal stent and preparation method thereof

Abstract

The present invention discloses a multi-material bionic structure tracheal stent and a preparation method thereof. The tracheal stent includes a TPU mechanical metamaterial structure layer, a hydrogel cell-carrying layer, a silicone mesh main body layer and a TPU cartilage ring layer stacked in sequence from the inside to the outside. The method includes: preparing the TPU mechanical metamaterial structure layer by a fused deposition four-axis printing method; printing the hydrogel cell-carrying layer on the outer layer of the TPU by an ink direct writing four-axis printing method; printing the silicone mesh main body layer on the outside of the hydrogel layer by an ink direct writing four-axis printing method; and printing multiple TPU cartilage ring layers outside the silicone layer by a fused deposition four-axis printing method to obtain a tracheal stent. The present invention can provide sufficient radial support while providing nonlinear mechanical properties that match the original trachea, solve the problem of stent displacement, and reproduce the inner wall ciliary tissue to realize the mucus cleaning function, avoiding the problem of mucus retention after stent implantation.

Description

Technical Field

[0001] The invention relates to a tracheal stent, in particular to a multi-material bionic structure tracheal stent and a preparation method thereof. Background Art

[0002] Tracheal stenosis mainly refers to the stenosis of the trachea, bronchi, and lobar bronchi. Among them, various factors: primary and metastatic malignant tumors, granulomatous lesions, organic tracheal stenosis, etc. cause a large proportion of the mortality rate. Compared with traditional surgery, tracheal stent implantation has the advantages of definite efficacy, rapid symptom relief, suitability for tracheal stenosis due to various causes, and reduced patient pain. The human tracheal wall is composed of tracheal cartilage and tracheal mucosa. Tracheal cartilage provides mechanical support, the ciliary tissue on the tracheal mucosa clears sputum, and smooth muscle collagen provides nonlinear mechanical properties for the trachea.

[0003] Currently, silicone stents and metal stents are used clinically. Metal stents have superior radial support performance, but the difference between the metal stent and the original tissue modulus is too large, resulting in a strong foreign body sensation. Silicone stents have less foreign body sensation, but the radial support performance is weaker than that of metal stents. Due to the diversity and complexity of human body movements, stents are prone to displacement or dislocation in the trachea because they do not have nonlinear mechanical properties that match the original trachea. After the tracheal stent is implanted, the outer wall of the stent compresses the inner wall of the trachea, causing the ciliated cells of the airway epithelium to be compressed. However, the free swinging of cilia is the main means for the trachea to clear mucus. Therefore, the implantation of tracheal stents will destroy the biological functionality of the trachea and easily cause mucus retention. Therefore, it is urgent to design a tracheal stent that can provide nonlinear mechanical properties that match the original trachea and can achieve mucus clearance by ciliary tissue on the inner wall of the stent. Summary of the invention

[0004] In order to solve the problems existing in the background technology, the present invention provides a multi-material bionic structure tracheal stent and a preparation method thereof, which provides sufficient radial support, nonlinear mechanical properties matching the original trachea and avoids the problem of mucus retention after stent implantation.

[0005] The technical solution adopted by the present invention is:

[0006] 1. A multi-material bionic structure tracheal stent:

[0007] The tracheal stent includes a TPU mechanical metamaterial structure layer, a hydrogel cell-carrying layer, a silicone mesh main layer and a TPU cartilage ring layer which are stacked in sequence from the inside to the outside. The TPU mechanical metamaterial structure layer, the hydrogel cell-carrying layer and the silicone mesh main layer are all tubular. The TPU cartilage ring layer includes a plurality of TPU cartilage rings, and each TPU cartilage ring is fixed on the outer side of the silicone mesh main layer at uniform intervals in sequence along the tube length direction of the tracheal stent, and the central axis of each TPU cartilage ring is on the central axis of the tracheal stent.

[0008] The TPU mechanical metamaterial structure layer adopts but is not limited to mechanical metamaterial structures such as chiral, concave or sinusoidal.

[0009] The TPU mechanical metamaterial structural layer is made of biocompatible medical silicone rubber material, specifically medical TPU material. In order to ensure that the aeroelastic modulus is close to that of the human body and to ensure compliance, medium hardness silicone is selected, and the Shore A hardness is 30°-50°; the layer thickness of the TPU mechanical metamaterial structural layer is less than or equal to 0.5mm to avoid the inner wall being too thick.

[0010] The hydrogel cell-carrying layer is made of porous methacrylated gelatin GelMA material; the thickness of the hydrogel cell-carrying layer is less than or equal to 0.5 mm to prevent the stent tube wall from being too thick; the pores of the hydrogel cell-carrying layer can provide space for cell growth.

[0011] The silicone mesh main body layer is made of biocompatible medical silicone rubber material. In order to ensure that the elastic modulus is close to that of the human body and to ensure compliance, low-hardness silicone is selected, and the Shore A hardness is 20°-40°; the thickness of the silicone mesh main body layer is less than or equal to 0.5mm. The silicone mesh main body layer adopts a bionic C-type mesh pore structure, which can provide a nutrient delivery channel for the hydrogel cell-carrying layer, allowing nutrients to pass through the inner wall of the stent to ensure the normal activity of cells.

[0012] Each TPU cartilage ring of the TPU cartilage ring layer is made of medical polyurethane TPU material, with a sufficiently large elastic modulus to provide radial support similar to that of tracheal cartilage, a Shore A hardness of the TPU cartilage ring greater than or equal to 95°, a Shore D hardness less than or equal to 65°, and a flexible and stretchable feature; the layer thickness of each TPU cartilage ring is 1.5-2.5 mm. The TPU cartilage ring can be specifically a bionic C-shaped TPU cartilage ring.

[0013] 2. A method for preparing a multi-material bionic structure tracheal stent:

[0014] The method comprises the following steps:

[0015] 1) The medical silicone rubber material is added to the fused deposition nozzle of the fused deposition four-axis printing platform, the external rotating shaft is heated to a constant temperature, and then the fused deposition nozzle prints the medical silicone rubber material on the outer peripheral surface of the external rotating shaft using the fused deposition four-axis printing method to form a tubular TPU mechanical metamaterial structure layer.

[0016] The fused deposition four-axis printing platform is a traditional three-axis printing platform with a linked heated rotating axis added. The medical TPU particles are prepared into filaments and added to the fused deposition nozzle. The wire is fed through the gears in the wire feeder. The nozzle head has a heating component, and the high-temperature molten metal is deposited on the rotating axis.

[0017] 2) Cool the external rotating shaft to room temperature, add the porous methacrylic gelatin GelMA material, i.e., hydrogel and silicone, to the ink direct writing nozzle of the ink direct writing four-axis printing platform, and then the ink direct writing nozzle uses the ink direct writing four-axis printing method to extrude the porous methacrylic gelatin GelMA material onto the outer peripheral surface of the TPU mechanical metamaterial structure layer by pneumatic extrusion or pressure rod extrusion to form a tubular hydrogel cell-carrying layer.

[0018] The ink direct writing four-axis printing platform is a fused deposition four-axis platform with an ink direct writing nozzle added.

[0019] 3) The medical silicone rubber material is added to the ink direct writing nozzle of the ink direct writing four-axis printing platform, and then the ink direct writing nozzle uses the ink direct writing four-axis printing method to extrude the medical silicone rubber material on the outer peripheral surface of the hydrogel cell-carrying layer by air pressure or pressure rod extrusion to form a tubular silicone mesh main body layer. After printing is completed, the external rotating shaft is heated to a constant temperature.

[0020] 4) The medical polyurethane TPU material is added to the fused deposition nozzle of the fused deposition four-axis printing platform, and then the fused deposition nozzle prints the medical polyurethane TPU material on the outer peripheral surface of the silicone mesh main layer using the fused deposition four-axis printing method to form a number of TPU cartilage rings evenly spaced along the tube length direction of the tracheal stent, and each TPU cartilage ring constitutes a TPU cartilage ring layer; after printing is completed, the external rotating shaft is cooled to room temperature, and then the final tracheal stent is removed from the external rotating shaft to obtain the final tracheal stent.

[0021] In the step 1), the medical silicone rubber material is specifically TPU filaments prepared from medical polyurethane TPU particles; in the step 3), the medical silicone rubber material is specifically a final mixed material of silicone and nano-silicon dioxide.

[0022] The final mixed material of silicone and nano silicon dioxide is as follows:

[0023] Nano-silicon dioxide and silicone with a mass fraction ratio of 5-30% are mixed to form a first mixed material, nano-silicon dioxide and silicone with a mass fraction ratio of 5-30% are mixed to form a second mixed material, and the first mixed material and the second mixed material are mixed to obtain a final mixed material; the mass fraction ratio of silicone in the first mixed material and the second mixed material is 1:1 or 10:1.

[0024] The first mixed material and the second mixed material are both liquid, and the final mixed material is solid, which can obtain good printability.

[0025] In the step 1), the external rotating shaft is heated to a constant temperature of 50°C-80°C; in the step 3), the external rotating shaft is heated to a constant temperature of 60°C-100°C.

[0026] The TPU cartilage ring layer is printed on the silicone mesh main body layer by a molten deposition nozzle. Since silicone itself is viscous, the rotating shaft 10 does not need to be heated in this step.

[0027] The beneficial effects of the present invention are:

[0028] The multi-material bionic structure tracheal stent of the present invention has an inner layer TPU metamaterial structure that can provide nonlinear mechanical properties to prevent problems such as stent displacement caused by mismatched mechanical properties. The hydrogel layer provides both an adhesive for the connection between TPU and silicone and an environment for cell growth, thereby reproducing the mucus clearing function of the real tracheal inner wall. The silicone mesh body mimics the tracheal mucosal structure, providing the stent with good biocompatibility and compliance, and the mesh pore structure can construct a nutrient delivery channel for the inner wall cells. The outer layer TPU cartilage ring structure uses a TPU material with high hardness and flexibility to provide the stent with good radial support performance. BRIEF DESCRIPTION OF THE DRAWINGS

[0029] Figure 1 Schematic diagram of the structure of the multi-material bionic structure tracheal stent of the present invention;

[0030] Figure 2 This is a cross-sectional view of the tube wall of the multi-material bionic structure tracheal stent of the present invention;

[0031] Figure 3 It is a schematic diagram of a dual-nozzle four-axis printing platform of the present invention;

[0032] Figure 4 is a flow chart of the preparation method of the present invention;

[0033] In the figure: 1. TPU mechanical metamaterial structure layer, 2. Hydrogel cell carrier layer, 3. Silicone mesh main body layer, 4. TPU cartilage ring layer, 5. TPU wire material, 6. Wire feeder, 7. Heating copper block nozzle, 8. Piston syringe, 9. Medical silicone rubber material, 10. Rotating axis, 11. Heating rod, 12. Temperature sensor. DETAILED DESCRIPTION

[0034] The present invention is further described in detail below with reference to the accompanying drawings and specific embodiments.

[0035] The specific embodiments of the present invention are as follows:

[0036] like Figure 1 and Figure 2As shown, the multi-material bionic structure tracheal stent includes four layers from inside to outside, which are TPU mechanical metamaterial structure layer 1, hydrogel cell-carrying layer 2, silicone mesh main body layer 3 and TPU cartilage ring layer 4. Figure 2 As shown, it is a cross-sectional view of the wall of the multi-material bionic structure tracheal stent. The TPU mechanical metamaterial structure layer 1 adopts a negative Poisson's ratio structure, that is, a sinusoidal mechanical metamaterial structure. The TPU mechanical metamaterial structure layer 1 adopts a biocompatible medical silicone rubber material, specifically a medical TPU material. In order to ensure that the aeroelastic modulus is close to that of the human body and to ensure compliance, a medium-hardness silicone is selected, and the Shore A hardness is 40°; the layer thickness of the TPU mechanical metamaterial structure layer 1 is 0.3mm to avoid excessive thickness of the inner wall. The hydrogel cell-carrying layer 2 adopts a porous methacrylated gelatin GelMA material; the layer thickness of the hydrogel cell-carrying layer 2 is 0.2mm to avoid too thick a stent wall; the pores of the hydrogel cell-carrying layer 2 can provide space for cell growth. The silicone mesh main body layer 3 adopts a biocompatible medical silicone rubber material. In order to ensure that the aeroelastic modulus is close to that of the human body and to ensure compliance, a low-hardness silicone is selected, and the Shore A hardness is 30°; the layer thickness of the silicone mesh main body layer 3 is 1.5mm. The silicone mesh main body layer 3 adopts a bionic C-type mesh pore structure, which can provide a nutrient delivery channel for the hydrogel cell-carrying layer, allowing nutrients to pass through the inner wall of the stent to ensure the normal activity of cells. Each TPU cartilage ring of the TPU cartilage ring layer 4 specifically adopts medical polyurethane TPU material, with a sufficiently large elastic modulus to provide a radial support force similar to that of tracheal cartilage. The Shore A hardness of the TPU cartilage ring is 95°, and it is flexible and stretchable; the layer thickness of each TPU cartilage ring is 2mm. The TPU cartilage ring can specifically be a bionic C-type TPU cartilage ring.

[0037] In the preparation process of the multi-material bionic structure tracheal stent of the present invention, a dual-nozzle four-axis printing platform is required. Figure 3 As shown, the dual-nozzle four-axis printing platform consists of a molten deposition nozzle that moves with a three-axis moving platform, an ink direct writing nozzle, and a linked heated rotating shaft 10, in which a heating rod 11 and a temperature sensor 12 are installed, and the heating rod 11 and the temperature sensor 12 are electrically connected.

[0038] like Figure 4 As shown, the preparation method of the multi-material bionic structure tracheal stent of the present invention is as follows:

[0039] 1) The medical silicone rubber material 9 is added to the fused deposition nozzle of the fused deposition four-axis printing platform through the piston syringe 8, that is, the TPU filament 5 prepared from the medical polyurethane TPU particles is added to the fused deposition nozzle of the fused deposition four-axis printing platform, the external rotating shaft 10 is heated to a constant temperature of 55°C, and then the fused deposition nozzle prints the medical TPU material on the outer peripheral surface of the external rotating shaft 10 using the fused deposition four-axis printing method to form a tubular TPU mechanical metamaterial structure layer 1.

[0040] The fused deposition four-axis printing platform is a traditional three-axis printing platform with an interlocked heated rotating shaft 10 added. The rotating shaft 10 is heated by an internal heating rod 11, and the temperature is observed and controlled by a temperature sensor 12. The material is added to the fused deposition nozzle, and the wire is fed through the gears in the wire feeder 6. The nozzle 7 of the nozzle head for heating the copper block has a heating component, and the high-temperature molten material is deposited on the rotating shaft 10.

[0041] 2) The external rotating shaft 10 is cooled to room temperature, and the hydrogel and silicone are added to the ink direct writing nozzle of the ink direct writing four-axis printing platform. Then, the ink direct writing nozzle uses the ink direct writing four-axis printing method to pneumatically extrude the porous methacrylated gelatin GelMA material onto the outer peripheral surface of the TPU mechanical metamaterial structure layer 1 to form a tubular hydrogel cell-carrying layer 2.

[0042] The ink direct writing four-axis printing platform is a fused deposition four-axis platform with an ink direct writing nozzle added.

[0043] 3) The piston syringe 8 of the medical silicone rubber material 9 is loaded into the ink direct writing nozzle of the ink direct writing four-axis printing platform, that is, the final mixed material of silicone and nano-silicon dioxide is loaded into the ink direct writing nozzle of the ink direct writing four-axis printing platform, and then the ink direct writing nozzle uses the ink direct writing four-axis printing method to extrude the medical silicone rubber material on the outer peripheral surface of the hydrogel cell carrier layer 2 to form a tubular silicone mesh main body layer 3. After printing is completed, the external rotating shaft 10 is heated to a constant temperature of 80°C.

[0044] 4) Add the medical polyurethane TPU material to the fused deposition nozzle of the fused deposition four-axis printing platform, and then the fused deposition nozzle prints the medical polyurethane TPU material on the outer peripheral surface of the silicone mesh main layer 3 using the fused deposition four-axis printing method to form a number of TPU cartilage rings evenly spaced along the tube length direction of the tracheal stent, and each TPU cartilage ring constitutes a TPU cartilage ring layer 4; after printing is completed, the external rotating shaft 10 is cooled to room temperature, and then the final tracheal stent is removed from the external rotating shaft 10 to obtain the final tracheal stent.

[0045] The final mixed material of silicone and nano-silicon dioxide is specifically, nano-silicon dioxide and silicone with a mass fraction ratio of 5% are mixed into a first mixed material, nano-silicon dioxide and silicone with a mass fraction ratio of 8% are mixed into a second mixed material, and the first mixed material and the second mixed material are mixed to obtain the final mixed material; the mass fraction ratio of silicone in the first mixed material and the second mixed material is 1:1. The first mixed material and the second mixed material are both liquids, and the final mixed material is solid, which can obtain good printability. The TPU cartilage ring layer 4 is printed on the silicone mesh main body layer 3 by a molten deposition nozzle. Since silicone itself is viscous, the rotating shaft 10 can also be heated in this step.

[0046] The embodiments described above provide a detailed description of the technical solutions and beneficial effects of the present invention. It should be understood that the above are only specific embodiments of the present invention and are not intended to limit the present invention. Any modifications, supplements and equivalent substitutions made within the scope of the principles of the present invention should be included in the protection scope of the present invention.

Claims

1. A multi-material bionic structure tracheal stent, characterized in that: The invention comprises a TPU mechanical metamaterial structure layer (1), a hydrogel cell-carrying layer (2), a silicone mesh main body layer (3) and a TPU cartilage ring layer (4) which are stacked in sequence from the inside to the outside. The TPU mechanical metamaterial structure layer (1), the hydrogel cell-carrying layer (2) and the silicone mesh main body layer (3) are all tubular. The TPU cartilage ring layer (4) comprises a plurality of TPU cartilage rings. Each TPU cartilage ring is fixed on the outer side surface of the silicone mesh main body layer (3) at uniform intervals in sequence along the tube length direction of the tracheal stent. The central axis of each TPU cartilage ring is on the central axis of the tracheal stent. The TPU mechanical metamaterial structure layer (1) adopts a chiral, concave or sinusoidal mechanical metamaterial structure.

2. The multi-material bionic structure tracheal stent according to claim 1, characterized in that: The TPU mechanical metamaterial structure layer (1) is made of TPU filaments (5) with a Shore A hardness of 30°-50°; the thickness of the TPU mechanical metamaterial structure layer (1) is less than or equal to 0.5 mm.

3. The multi-material bionic structure tracheal stent according to claim 1, characterized in that: The hydrogel cell-carrying layer (2) is made of porous methacrylated gelatin GelMA material; the thickness of the hydrogel cell-carrying layer (2) is less than or equal to 0.5 mm.

4. The multi-material bionic structure tracheal stent according to claim 1, characterized in that: The silicone mesh main body layer (3) is made of medical silicone rubber material with a Shore A hardness of 20°-40°; the thickness of the silicone mesh main body layer (3) is less than or equal to 0.5 mm.

5. The multi-material bionic structure tracheal stent according to claim 1, characterized in that: Each TPU cartilage ring of the TPU cartilage ring layer (4) is made of medical polyurethane TPU material, the Shore A hardness of the TPU cartilage ring is greater than or equal to 95°, and the Shore D hardness is less than or equal to 65°; the layer thickness of each TPU cartilage ring is 1.5-2.5 mm.

6. A method for preparing a multi-material bionic structure tracheal stent according to any one of claims 1 to 5, characterized in that: The method comprises the following steps: 1) The TPU filament (5) is added to the fused deposition nozzle of the fused deposition four-axis printing platform, the external rotating shaft (10) is heated to a constant temperature, and then the fused deposition nozzle prints the TPU filament (5) on the outer peripheral surface of the external rotating shaft (10) using the fused deposition four-axis printing method to form a tubular TPU mechanical metamaterial structure layer (1); 2) Cooling the external rotating shaft (10) to room temperature, adding the porous methacrylic gelatin GelMA material to the ink direct writing nozzle of the ink direct writing four-axis printing platform, and then the ink direct writing nozzle uses the ink direct writing four-axis printing method to extrude the porous methacrylic gelatin GelMA material on the outer peripheral surface of the TPU mechanical metamaterial structure layer (1) by air pressure or pressure rod extrusion to form a tubular hydrogel cell carrier layer (2); 3) adding the medical silicone rubber material to the ink direct writing nozzle of the ink direct writing four-axis printing platform, and then the ink direct writing nozzle uses the ink direct writing four-axis printing method to extrude the medical silicone rubber material by air pressure or pressure rod extrusion to print on the outer peripheral surface of the hydrogel cell-carrying layer (2) to form a tubular silicone mesh main body layer (3), and after printing is completed, the external rotating shaft (10) is heated to a constant temperature; 4) Adding medical polyurethane TPU material to the fused deposition nozzle of the fused deposition four-axis printing platform, and then the fused deposition nozzle prints the medical polyurethane TPU material on the outer peripheral surface of the silicone mesh main layer (3) using the fused deposition four-axis printing method to form a plurality of TPU cartilage rings evenly spaced along the tube length direction of the tracheal stent, each TPU cartilage ring constituting a TPU cartilage ring layer (4); after printing is completed, the external rotating shaft (10) is cooled to room temperature, and then the final tracheal stent is removed from the external rotating shaft (10) to obtain the final tracheal stent.

7. The method for preparing a multi-material bionic structure tracheal stent according to claim 6, characterized in that: In the step 1), the TPU filament (5) is specifically prepared from medical polyurethane TPU particles; in the step 3), the medical silicone rubber material is specifically a final mixed material of silicone and nano-silicon dioxide.

8. The method for preparing a multi-material bionic structure tracheal stent according to claim 7, characterized in that: The final mixed material of silicone and nano silicon dioxide is as follows: Nano-silicon dioxide and silicone with a mass fraction ratio of 5-30% are mixed to form a first mixed material, nano-silicon dioxide and silicone with a mass fraction ratio of 5-30% are mixed to form a second mixed material, and the first mixed material and the second mixed material are mixed to obtain a final mixed material; the mass fraction ratio of silicone in the first mixed material and the second mixed material is 1:1 or 10:

1.

9. The method for preparing a multi-material bionic structure tracheal stent according to claim 6, characterized in that: In the step 1), the external rotating shaft (10) is heated to a constant temperature of 50°C-80°C; in the step 3), the external rotating shaft (10) is heated to a constant temperature of 60°C-100°C.

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