Intervertebral disc nucleus pulposus stent and preparation method thereof

Abstract

The invention discloses an intervertebral disc nucleus pulposus stent and a preparation method thereof, and belongs to the technical field of medical instruments.The preparation method comprises the steps that PLLA, TMC and GA are dissolved in a solvent, and a polymer solution is prepared; the preparation method comprises the following steps: printing a polymer solution on a cooling platform layer by layer through a 3D printer to prepare an octagonal prism with a pore structure inside, and then drying the octagonal prism to prepare a precursor; and performing plasma treatment on the precursor to obtain the composite material. The stent has the mechanical property similar to that of the intervertebral disc of a human body, and mechanical fatigue can be relieved; meanwhile, the material of the stent has good biocompatibility, the inflammation risk generated by degradation products is small, and the problems existing in an existing stent can be effectively solved.

Description

Technical Field

[0001] The present invention belongs to the technical field of medical devices, and in particular relates to an intervertebral disc nucleus pulposus scaffold and a preparation method thereof. Background Art

[0002] At present, common solutions for intervertebral disc nucleus pulposus replacement include the following categories: polymer hydrogel materials: such as polyethylene glycol (PEG) and polyvinyl alcohol (PVA) hydrogels, which are often used to repair and fill the nucleus pulposus due to their excellent elasticity and water absorption. However, these materials have poor mechanical strength and cannot reach the mechanical strength of natural nucleus pulposus. They also degrade too quickly and cannot provide good mechanical support while repairing.

[0003] Bioceramic and metal stents: such as titanium alloy stents, although they have high mechanical strength, lack elastic matching with soft tissue and are prone to cause stress shielding effect on surrounding vertebrae.

[0004] Thermoplastic polymer scaffolds: For example, pure PLLA (poly-L-lactic acid) scaffolds have high rigidity and their degradation products are acidic, which can easily cause osteolysis.

[0005] In summary, the main shortcomings of the existing technology are:

[0006] 1. Single material properties: Existing materials are difficult to simultaneously take into account mechanical properties, biocompatibility and degradation behavior, which often leads to tissue repair failure or inflammatory response.

[0007] 2. Inadequate structural design: Bracket designs are mostly regular shapes, such as cylinders or honeycombs, which cannot effectively disperse the load or simulate the complex deformation behavior of the intervertebral disc.

[0008] 3. The implantation method cannot be minimally invasive: Traditional preparation methods are limited to fixed shapes, so a larger incision is required to implant the corresponding material. This material can achieve shape memory, be compressed at room temperature, and can automatically recover into a customized structure after entering the body. Summary of the Invention

[0009] In response to the above-mentioned deficiencies in the prior art, the present invention provides an intervertebral disc nucleus pulposus scaffold and a preparation method thereof. The scaffold has mechanical properties similar to those of the human body's own intervertebral disc and can reduce mechanical fatigue. At the same time, the material of the scaffold has good biocompatibility, and the risk of inflammation caused by degradation products is relatively low, which can effectively solve the problems existing in existing scaffolds.

[0010] To achieve the above-mentioned purpose, the technical solution adopted by the present invention to solve the technical problem is:

[0011] A method for preparing an intervertebral disc nucleus pulposus scaffold comprises the following steps:

[0012] (1) dissolving PLLA, TMC and GA in a solvent to prepare a polymer solution;

[0013] (2) The polymer solution is printed layer by layer on a cooling platform by a 3D printer to obtain an octagonal prism precursor with a porous structure inside, which is then dried to obtain the product.

[0014] Furthermore, in step (1), the mass ratio of PLLA, TMC and GA is 45-60:20-30:20-30.

[0015] Furthermore, the mass fraction of the polymer solution in step (1) is 10% to 30%.

[0016] Furthermore, in step (1), the solvent is 1,4-dioxane.

[0017] Furthermore, in step (2), the printing temperature is -10°C to 25°C, the nozzle diameter is 0.2 to 0.4 mm, the cooling platform temperature is -4°C to -50°C, the layer thickness is 0.1 to 0.4 mm, and the printing speed is 10 to 30 mm / s.

[0018] Furthermore, the octagonal prism precursor with a porous structure in step (2) is made by stacking several layers of base layers, wherein the base layers are made of octagonal rings with different side lengths and straight lines connecting the octagonal rings diagonally.

[0019] Furthermore, there are at least four octagonal rings.

[0020] An intervertebral disc nucleus pulposus scaffold is manufactured by adopting the above method.

[0021] The beneficial effects produced by the present invention are:

[0022] 1. The present invention uses poly-L-lactic acid (PLLA), trimethylene carbonate (TMC) and glycerol (GA) as raw materials. The three raw materials are polymerized in a specific ratio to form a polymer. The polymer has both rigidity and flexibility, and its mechanical properties are closer to those of a natural intervertebral disc, which can effectively improve the patient's use effect. Among them, PLLA provides mechanical strength for the stent, TMC can increase the flexibility of the stent and reduce mechanical fatigue, and GA can regulate the degradation rate of the stent and promote tissue repair on the stent. The degradation rate of the stent can be controlled within 12 to 24 months, and the pH value of the degradation product changes little, which significantly reduces the risk of inflammation.

[0023] 2. The present invention adopts a 3D printer to print and prepare the intervertebral disc scaffold structure, so that the prepared intervertebral disc scaffold structure is closer to the human body's own intervertebral disc structure, with smaller dimensional error, and can be customized according to the individual to adapt to the needs of different patients; at the same time, by adjusting the printing speed, temperature and solvent evaporation rate, etc., the internal structural stability of the intervertebral disc scaffold can be improved to avoid the collapse of the scaffold.

[0024] 3. The scaffold prepared in the present invention is an octagonal prism, and the internal symmetrical distribution of the structure can reduce stress concentration and improve the overall mechanical stability of the scaffold; the scaffold has a uniformly distributed pore structure inside, which can promote cell proliferation and nutrient penetration. BRIEF DESCRIPTION OF THE DRAWINGS

[0025] Figure 1 This is a physical picture of the intervertebral disc nucleus pulposus scaffold;

[0026] Figure 2 This is the state diagram of the intervertebral disc nucleus pulposus scaffold changing with temperature;

[0027] Figure 3 A is a schematic diagram of printing condition screening, A is a schematic diagram of printing conditions, and B is a schematic diagram of printing status;

[0028] Figure 4 This is an electron microscopic image of the interior of the intervertebral disc nucleus pulposus;

[0029] Figure 5 This is a diagram of the metabolic results in animals. DETAILED DESCRIPTION

[0030] In order to make the purpose, technical solutions and advantages of the present invention more clearly understood, the present invention is further described in detail below in conjunction with the embodiments. It should be understood that the specific embodiments described herein are only used to explain the present invention and are not intended to limit the present invention. That is, the embodiments described are only part of the embodiments of the present invention, rather than all embodiments.

[0031] Therefore, the detailed description of the embodiments of the present invention provided below is not intended to limit the scope of the invention as claimed, but is merely intended to represent selected embodiments of the present invention. All other embodiments obtained by those skilled in the art based on the embodiments of the present invention without creative work are within the scope of protection of the present invention.

[0032] It should be noted that relational terms such as "first" and "second" are used only to distinguish one entity or operation from another entity or operation, and do not necessarily require or imply any actual relationship or order between these entities or operations. Moreover, the terms "comprises," "comprising," or any other variations thereof are intended to cover non-exclusive inclusion, such that a process, method, article, or apparatus comprising a series of elements includes not only those elements, but also other elements not explicitly listed, or elements inherent to such process, method, article, or apparatus. In the absence of further limitations, an element defined by the phrase "comprising a ..." does not exclude the presence of other identical elements in the process, method, article, or apparatus comprising the element.

[0033] The features and performance of the present invention are further described in detail below with reference to the embodiments and drawings.

[0034] Example 1

[0035] A method for preparing an intervertebral disc nucleus pulposus scaffold comprises the following steps:

[0036] (1) PLLA, TMC, and GA were dissolved in 1,4-dioxane solvent at 40°C in a mass ratio of 56:24:20 to prepare a polymer solution (PLTG) with a GA mass fraction of 20%, wherein the mass volume ratio of PLTG to 1,4-dioxane solvent was 1:5;

[0037] (2) The polymer solution was printed into five octagonal rings from the inside out or from the outside in on a cooling platform at -4°C using a 3D printer. The overlapping octagonal rings were then connected diagonally to form a spider web structure. The structure was printed layer by layer to obtain an octagonal prism with a porous structure inside. The octagonal prism was then placed under -4°C for vacuum drying to obtain an intervertebral disc nucleus pulposus scaffold. The specific printing parameters were: printing temperature of -10°C, nozzle diameter of 0.2 mm, layer thickness of 0.1 mm, and printing speed of 10 mm / s.

[0038] Example 2

[0039] A method for preparing an intervertebral disc nucleus pulposus scaffold comprises the following steps:

[0040] (1) PLLA, TMC, and GA were dissolved in 1,4-dioxane solvent at 50°C in a mass ratio of 63:27:10 to prepare a polymer solution (PLTG) with a GA mass fraction of 10%, wherein the mass volume ratio of PLTG to 1,4-dioxane solvent was 1:4;

[0041] (2) The polymer solution was printed into multiple octagonal rings from the inside out or from the outside in on a cooling platform at -4°C using a 3D printer. The diagonals of the overlapping octagonal rings were then connected to form a spider web structure. The structure was printed layer by layer to obtain an octagonal prism with a porous structure inside. The octagonal prism was then placed under -4°C for vacuum drying to obtain an intervertebral disc nucleus pulposus scaffold. The specific printing parameters were: printing temperature of 15°C, nozzle diameter of 0.4 mm, layer thickness of 0.4 mm, and printing speed of 30 mm / s.

[0042] Example 3

[0043] A method for preparing an intervertebral disc nucleus pulposus scaffold comprises the following steps:

[0044] (1) PLLA, TMC, and GA were dissolved in 1,4-dioxane solvent at 40°C in a mass ratio of 49:21:30 to prepare a polymer solution (PLTG) with a GA mass fraction of 30%, wherein the mass volume ratio of PLTG to 1,4-dioxane solvent was 1:6;

[0045] (2) The polymer solution was printed into multiple octagonal rings from the inside out or from the outside in on a cooling platform at -4°C using a 3D printer. The diagonals of the overlapping octagonal rings were then connected to form a spider web structure. The structure was printed layer by layer to obtain an octagonal prism with a porous structure inside. The octagonal prism was then placed under -4°C for vacuum drying to obtain an intervertebral disc nucleus pulposus scaffold. The specific printing parameters were: printing temperature of 25°C, nozzle diameter of 0.3 mm, layer thickness of 0.3 mm, and printing speed of 20 mm / s.

[0046] Test example

[0047] Taking the stent in Example 1 as an example, the mechanical properties of different stents were measured. The specific results are shown in Table 1.

[0048] Table 1: Mechanical properties test results

[0049] Material Type Elastic modulus (MPa) Pure PLLA material ≥10MPa Example 1 3MPa Natural intervertebral disc nucleus pulposus 1-4MPa

[0050] It can be seen from the test results in the above table that the intervertebral disc scaffold prepared in Example 1 of the present application has a mechanical strength closer to that of a natural intervertebral disc.

[0051] Figure 1 This is a real-life picture of an intervertebral disc nucleus pulposus scaffold. It is a three-dimensional octagonal prism with multiple pore structures inside.

[0052] Figure 2 This is a state diagram of the intervertebral disc nucleus pulposus scaffold changing with temperature. It can be seen that after the scaffold is folded and frozen at low temperature, the shape of the scaffold can automatically recover at 37℃.

[0053] Figure 3 This is a schematic diagram of printing condition screening. It can be seen that PLTG solutions with different mass concentrations have different printing states at 15, 25, and 35°C.

[0054] Figure 4 This is an electron microscope image of the interior of the intervertebral disc nucleus pulposus. It can be seen that the interior of the scaffold has a porous structure, which is more conducive to cell growth.

[0055] Figure 5 Figure 3 is the result of animal volume metabolism. A: The PLTG scaffold was co-cultured with nucleus pulposus cells, and live-dead cell staining was performed on the 1st, 3rd, and 5th days after culture. The results showed that the PLTG scaffold had good biocompatibility and the nucleus pulposus cells survived well after co-culture. B: The PLTG scaffold was co-cultured with nucleus pulposus cells, and cytoskeleton staining was performed on the 1st and 3rd days after culture. The results showed that the scaffold had no effect on the cytoskeleton of nucleus pulposus cells after co-culture. C: The PLTG scaffold was stained and implanted subcutaneously in rats, and in vivo imaging was performed at 2 weeks and 4 weeks, indicating that the scaffold had good biocompatibility and slow degradation. D: The PLTG immersion solution was co-cultured with nucleus pulposus cells, and CCK test was performed on the 1st, 2nd, and 3rd days, respectively. The results showed that the scaffold had no effect on cell viability. In summary, the PLTG scaffold has good biocompatibility, no cytotoxicity, and high biosafety.

Claims

1. A method for preparing an intervertebral disc nucleus pulposus scaffold, characterized in that: The following steps are involved: (1) dissolving PLLA, TMC and GA in a solvent to prepare a polymer solution; (2) The polymer solution is printed layer by layer on a cooling platform by a 3D printer to obtain an octagonal prism precursor with a porous structure inside, which is then dried to obtain the product.

2. The method for preparing an intervertebral disc nucleus pulposus scaffold according to claim 1, wherein: The mass ratio of PLLA, TMC and GA in step (1) is 49-63:21-27:10-30.

3. The method for preparing the intervertebral disc nucleus pulposus scaffold according to claim 1, wherein: The mass fraction of the polymer solution in step (1) is 10% to 30%.

4. The method for preparing an intervertebral disc nucleus pulposus scaffold according to claim 1, wherein: The solvent in step (1) is 1,4-dioxane.

5. The method for preparing an intervertebral disc nucleus pulposus scaffold according to claim 1, wherein: In step (2), the printing temperature is -10°C to 25°C, the nozzle diameter is 0.2 to 0.4 mm, the cooling platform temperature is -4°C to -50°C, the layer thickness is 0.1 to 0.4 mm, and the printing speed is 10 to 30 mm / s.

6. The method for preparing an intervertebral disc nucleus pulposus scaffold according to claim 1, wherein: The octagonal prism precursor with a porous structure in step (2) is made by stacking several layers of base layers, wherein the base layers are made of octagonal rings with different side lengths and straight lines connecting the octagonal rings diagonally.

7. The method for preparing an intervertebral disc nucleus pulposus scaffold according to claim 6, wherein: There are at least four octagonal rings.

8. An intervertebral disc nucleus pulposus scaffold, characterized in that: The method according to any one of claims 1 to 7 is used.

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