PET bag of interbody fusion cage and preparation method of PET bag

Abstract

The invention discloses an interbody fusion cage PET bag and a preparation method thereof.The preparation method comprises the steps that an acid solution or an alkaline solution is adopted for treating the surface of the PET bag, then plasma treatment is conducted on the surface of the PET bag, and the surface-treated PET bag is obtained; placing the PET bag subjected to surface treatment in an NHS solution, carrying out ultrasonic treatment to obtain an activated PET bag, adding the activated PET bag and glycerin into a PBS solution, and carrying out a stirring reaction to obtain a pretreated PET bag; placing the pretreated PET bag and BMP in an NHS solution, and carrying out an ultrasonic reaction to obtain a BMP-fixed PET bag; placing the PET bag fixed with the BMP in a PBS solution for heat treatment; according to the preparation method disclosed by the invention, the biocompatibility and osteoinductivity of the PET capsule are improved, the growth and repair of bone tissues can be promoted, and the problem that the existing PET capsule material is insufficient in bone regeneration efficiency is effectively solved.

Description

Technical Field

[0001] The present invention relates to the technical field of PET materials, and particularly relates to an intervertebral fusion PET sac and a preparation method thereof. Background Art

[0002] Spinal endoscopy technology is at the forefront of the field of minimally invasive spine surgery. It provides a clear surgical field for spinal surgery with a revolutionary water medium, greatly reducing the trauma of surgery. Currently, through spinal endoscopy, procedures such as discectomy and laminectomy for spinal canal decompression can be carried out relatively maturely, achieving nerve decompression. In addition to decompression, fixation and spinal fusion are key technologies in spinal surgery to achieve temporary and long-term stability. Currently, pedicle screws can be minimally invasively implemented through percutaneous screw placement technology, but most current bone graft fusion devices are made of rigid structural materials such as titanium alloy and PEEK, with relatively high rigidity, which is likely to cause endplate damage and ultimately lead to the collapse of the fusion device and fusion failure.

[0003] In order to improve the fusion effect, in the prior art, a smaller working cannula is directly inserted into the intervertebral space, and then an expandable PET (polyethylene terephthalate) woven balloon device is placed. Then, bone grafting materials are filled into the balloon through the cannula, which greatly reduces the difficulty of bone graft fusion and can significantly reduce the probability of nerve injury, showing a certain degree of advancement. This is because PET material, as a polymer material, has excellent physical properties and chemical stability, enabling the balloon to maintain a stable shape and mechanical properties during expansion. However, traditional PET materials have no osteoinductive effect in biomedical applications, cannot promote osteogenesis, and are prone to bone fusion failure. Summary of the Invention

[0004] The purpose of the present invention is to provide an intervertebral fusion PET sac and a preparation method thereof. The preparation method forms a stable BMP (bone morphogenetic protein) layer on the surface of the PET sac to enhance the biocompatibility and osteoinductivity of the PET sac, thereby promoting bone tissue growth and repair and solving the problem of insufficient efficiency of existing PET sac materials in bone regeneration.

[0005] To achieve the above purpose of the present invention, the following technical solutions are specifically adopted:

[0006] The first aspect of the present invention provides a preparation method of an intervertebral fusion PET sac, and the preparation method includes the following steps:

[0007] (a) Surface treatment:

[0008] The surface of the PET sac is treated with an acidic solution or an alkaline solution, and then the surface of the PET sac is subjected to plasma treatment to obtain a surface-treated PET sac;

[0009] (b) Introduction of activation and linking molecules:

[0010] Place the surface-treated PET sachet in an NHS solution and sonicate to obtain an activated PET sachet. Then add the activated PET sachet and glycerol to a PBS solution and stir to react to obtain a pretreated PET sachet.

[0011] (c) Fixation of BMP:

[0012] Place the pretreated PET sachet and BMP in an NHS (N-hydroxysuccinimide) solution and perform a sonication reaction to obtain a PET sachet with BMP fixed thereon.

[0013] (d) Stabilization and optimization:

[0014] Place the PET sachet with BMP fixed thereon in a PBS solution for heat treatment to obtain the PET sachet of the intervertebral fusion device.

[0015] In the preparation method of the present invention, by using plasma treatment on the surface of the PET sachet in (a), polar groups (such as hydroxyl and carboxyl groups) are formed and the surface roughness is increased to facilitate the binding of BMP; in (b), a surface activator is used to provide a stable covalent bond to link BMP; in (c), through a fixation technique, BMP forms a firm bond with the surface of the pretreated PET; finally, in (d), through heat treatment, BMP adheres more tightly to the PET surface while reducing the loss during application; the above preparation method can ensure the stable presence of BMP on the surface of the PET sachet, improve the biocompatibility and bone regeneration function of the PET sachet, and is suitable for wide applications in orthopedic implants and tissue engineering.

[0016] In addition, after treating the surface of the PET sachet with an acidic or alkaline solution in step (a) of the present invention, hydrophobic groups can be removed; subsequently, high-energy particles in the plasma generated by the gas physically bombard the PET surface through ion and free radical high-speed impacts, causing surface micro-etching, thereby increasing the surface roughness, which helps macromolecules such as BMP to adhere to the surface; at the same time, active free radicals and oxygen plasma in the plasma will react with carbon atoms on the PET molecular chain to introduce new functional groups. For oxygen plasma treatment, polar groups such as hydroxyl (-OH) and carboxyl (-COOH) will be generated, thereby enhancing the hydrophilicity and polarity of the PET surface and providing active sites for the binding of BMP; in addition, the plasma may also cause chain breakage or cross-linking of the PET chain, further changing the surface chemical properties and binding ability. In this step, the pressure in the plasma reaction chamber is 0.1 - 1 Pa, the high-frequency electric field power is 10 - 100 W, the treatment time of argon is 8 - 12 seconds, and the treatment time of oxygen is 50 - 70 seconds. This is because the higher the power, the stronger the surface etching effect, but too high power may damage the PET material. At the same time, the longer the time, the more functional groups are generated, but it may also lead to over-etching or material damage. As time increases, the polar groups and roughness on the PET surface gradually increase.

[0017] Preferably, in the step (a), the acidic solution is a dilute hydrochloric acid solution; the alkaline solution is a sodium hydroxide solution or a potassium hydroxide solution; the pH value of the acidic solution is 6.2 - 6.6; the pH value of the alkaline solution is 7.5 - 8.0; the treatment method is to immerse the PET sachet in the acidic solution or the alkaline solution for 1 - 2 min.

[0018] Preferably, in the step (a), the plasma treatment of the PET sachet surface includes: placing the PET sachet in a plasma reaction chamber, and then passing argon and oxygen through a high-frequency electric field in sequence to generate plasma to impact the PET sachet surface;

[0019] The pressure in the plasma reaction chamber is 0.1 - 1 Pa, and the high-frequency electric field power is 10 - 100 W;

[0020] The argon introduction time is 8 - 12 s; the oxygen introduction time is 50 - 70 s.

[0021] Preferably, in the step (b), the concentration of the NHS solution is 12 - 18 mmol / L, and the pH value is 7.1 - 7.5; the ultrasonic treatment temperature is 35 - 40 °C, and the time is 15 - 25 s.

[0022] Preferably, in the step (b), the pH value of the PBS solution is 6.2 - 6.5, the final added concentration of glycerol is 1% - 3%, the stirring reaction time is 25 - 35 s, and the stirring speed is 8 - 12 rpm.

[0023] Preferably, in the step (c), the concentration of the NHS solution is 12 - 18 mmol / L; the ultrasonic reaction time is 4 - 6 min.

[0024] Preferably, in the step (c), the final concentration of BMP is 4 - 8 mg / mL; the mass - to - volume ratio of the PET sachet to the NHS solution is 1∶(8 - 12).

[0025] Preferably, in the step (d), the heat treatment temperature is 40 - 50 °C and the time is 4 - 6 min.

[0026] The second aspect of the present invention provides an intervertebral fusion device PET sachet prepared by the above - mentioned preparation method.

[0027] Compared with the prior art, the beneficial effects of the present invention at least include:

[0028] By modifying the surface of the PET sachet to increase BMP, the present invention can effectively promote cell adhesion and proliferation, reduce inflammatory reactions, improve the biosafety of the material, and promote bone tissue regeneration: solving the problem of insufficient efficiency of existing PET sachets in bone regeneration; at the same time, it expands the application of PET materials in the medical field, and overcomes the limitations of traditional PET materials in the application of medical fields such as orthopedic implants, providing a new way for the application of PET materials in fields such as orthopedics and stomatology, and having high practical value.

[0029] In the prior art, most are rigid materials such as PEEK and titanium alloy, and expandable sachet intervertebral fusion devices are very scarce. Although PET materials have certain biocompatibility, they lack osteoinductive properties and are not conducive to bone tissue regeneration and repair; however, by coating a material with osteoinductive properties (bone morphogenetic protein BMP) on the surface of the PET sachet, the present invention significantly improves the biocompatibility and osteoinductive properties of the material; this is not only conducive to bone tissue regeneration and repair, but also can reduce complications of intervertebral fusion, such as wound infection, deep intervertebral space infection, non - union, etc. Detailed Embodiments

[0030] The following will describe in detail the embodiments of the technical solutions of the present invention in combination with the embodiments. The following embodiments are only used to more clearly illustrate the technical solutions of the present invention, so they are only examples and cannot be used to limit the protection scope of the present invention.

[0031] It should be noted that unless otherwise specified, the technical terms or scientific terms used in this application should have the ordinary meaning understood by those skilled in the art to which the present invention belongs.

[0032] Example 1

[0033] This embodiment is a preparation method of a PET sac for an intervertebral fusion device, and the preparation method includes the following steps:

[0034] (a) Surface treatment:

[0035] Immerse the PET sac in a hydrochloric acid solution with a pH value of 6.5 for 1 minute, drain, rinse, and dry it. Then place the PET sac in a plasma reaction chamber, and pass argon and oxygen through a high-frequency electric field in sequence to generate plasma to impact the surface of the PET sac, obtaining a surface-treated PET sac. Among them, the pressure in the plasma reaction chamber is 0.1 Pa, the power of the high-frequency electric field is 100 W; the argon introduction time is 8 s; the oxygen introduction time is 50 s;

[0036] (b) Activation and introduction of linking molecules:

[0037] Place the surface-treated PET sac in an NHS solution with a concentration of 12 mmol / L and a pH value of 7.1, and perform ultrasonic treatment for 15 s at 40 °C to obtain an activated PET sac. Then add the activated PET sac and glycerol to a PBS solution and stir to react, obtaining a pretreated PET sac. Among them, the pH value of the PBS solution is 6.2, the final concentration of glycerol added is 1%, the stirring reaction time is 25 s, and the stirring speed is 8 rpm;

[0038] (c) BMP fixation:

[0039] Place the pretreated PET sac and BMP in an NHS solution and perform ultrasonic reaction to obtain a PET sac with BMP fixed. Among them, the concentration of the NHS solution is 12 mmol / L; the ultrasonic reaction time is 6 min; the final concentration of BMP is 4 mg / mL; the mass-volume ratio of the PET sac to the NHS solution is 1:12;

[0040] (d) Stabilization and optimization:

[0041] Place the PET sac with BMP fixed in a PBS solution and perform heat treatment at 40 °C for 6 min to obtain the PET sac for the intervertebral fusion device.

[0042] Example 2

[0043] This embodiment is a preparation method of a PET sac for an intervertebral fusion device, and the preparation method includes the following steps:

[0044] (a) Surface treatment:

[0045] The PET sachet was immersed in a sodium hydroxide solution with a pH value of 7.8 for 2 min, drained, rinsed, and air-dried. Then the PET sachet was placed in a plasma reaction chamber, and argon and oxygen were successively passed through a high-frequency electric field to generate plasma to impact the surface of the PET sachet, obtaining a surface-treated PET sachet. Among them, the pressure in the plasma reaction chamber was 1 Pa, the power of the high-frequency electric field was 10 W; the argon introduction time was 12 s; the oxygen introduction time was 70 s;

[0046] (b) Activation and introduction of linking molecules:

[0047] The surface-treated PET sachet was placed in an NHS solution with a concentration of 18 mmol / L and a pH value of 7.5 and ultrasonically treated at 35 °C for 25 s to obtain an activated PET sachet. Then the activated PET sachet and glycerol were added to a PBS solution and stirred for reaction to obtain a pretreated PET sachet. Among them, the pH value of the PBS solution was 6.5, the final concentration of glycerol added was 3%, the stirring reaction time was 35 s, and the stirring speed was 12 rpm;

[0048] (c) BMP immobilization:

[0049] The pretreated PET sachet and BMP were placed in an NHS solution and ultrasonically oscillated to obtain a PET sachet with immobilized BMP. Among them, the concentration of the NHS solution was 18 mmol / L; the ultrasonic reaction time was 4 min; the final concentration of BMP was 8 mg / mL; the mass-volume ratio of the PET sachet to the NHS solution was 1:8;

[0050] (d) Stabilization and optimization:

[0051] The PET sachet with immobilized BMP was heat-treated in a PBS solution at 50 °C for 4 min to obtain the PET sachet of the intervertebral fusion device.

[0052] Example 3

[0053] This example is a preparation method of a PET sachet of an intervertebral fusion device, and the preparation method includes the following steps:

[0054] (a) Surface treatment:

[0055] The PET sachet was immersed in a hydrochloric acid solution with a pH value of 6.5 for 1.5 min, drained, rinsed, and air-dried. Then the PET sachet was placed in a plasma reaction chamber, and argon and oxygen were successively passed through a high-frequency electric field to generate plasma to impact the surface of the PET sachet, obtaining a surface-treated PET sachet. Among them, the pressure in the plasma reaction chamber was 0.5 Pa, the power of the high-frequency electric field was 50 W; the argon introduction time was 10 s; the oxygen introduction time was 60 s;

[0056] (b) Activation and introduction of linking molecules:

[0057] The surface-treated PET sac is placed in an NHS solution with a concentration of 15 mmol / L and a pH value of 7.2 and ultrasonically treated at 40 °C for 20 s to obtain an activated PET sac. Then, the activated PET sac and glycerol are added to a PBS solution for stirring reaction to obtain a pretreated PET sac, where the pH value of the PBS solution is 6.3, the final concentration of glycerol added is 2%, the stirring reaction time is 30 s, and the stirring speed is 10 rpm;

[0058] (c) BMP immobilization:

[0059] The pretreated PET sac and BMP are placed in an NHS solution for ultrasonic reaction to obtain a PET sac with immobilized BMP, where the concentration of the NHS solution is 15 mmol / L; the ultrasonic reaction time is 5 min; the final concentration of BMP is 6 mg / mL; the mass-volume ratio of the PET sac to the NHS solution is 1:10;

[0060] (d) Stabilization and optimization:

[0061] The PET sac with immobilized BMP is heat-treated in a PBS solution at 45 °C for 5 min to obtain the PET sac of the intervertebral fusion device.

[0062] Comparative Example 1

[0063] This comparative example is a preparation method of a PET sac of an intervertebral fusion device, and the preparation method includes the following steps:

[0064] (a) Surface treatment:

[0065] The PET sac is immersed in a hydrochloric acid solution with a pH value of 6.5 for 1.5 min, drained, rinsed, and dried. Then, the PET sac is placed in a plasma reaction chamber, and argon is passed through a high-frequency electric field to generate plasma to impact the surface of the PET sac to obtain a surface-treated PET sac, where the pressure in the plasma reaction chamber is 0.5 Pa, the power of the high-frequency electric field is 50 W; the argon introduction time is 70 s;

[0066] (b) Activation and introduction of linking molecules:

[0067] The surface-treated PET sac is placed in an NHS solution with a concentration of 15 mmol / L and a pH value of 7.2 and ultrasonically treated at 40 °C for 20 s to obtain an activated PET sac. Then, the activated PET sac and glycerol are added to a PBS solution for stirring reaction to obtain a pretreated PET sac, where the pH value of the PBS solution is 6.3, the final concentration of glycerol added is 2%, the stirring reaction time is 30 s, and the stirring speed is 10 rpm;

[0068] (c) BMP immobilization:

[0069] The pretreated PET pouch and BMP were placed in an NHS solution and subjected to ultrasonic reaction to obtain a PET pouch with immobilized BMP. Among them, the concentration of the NHS solution was 15 mmol / L; the ultrasonic reaction time was 5 min; the final concentration of BMP was 6 mg / mL; the mass-volume ratio of the PET pouch to the NHS solution was 1:10;

[0070] (d) Stabilization and optimization:

[0071] The PET pouch with immobilized BMP was placed in a PBS solution and heat-treated at 45 °C for 5 min to obtain the PET pouch of the intervertebral fusion device.

[0072] Comparative Example 2

[0073] This comparative example is a preparation method of a PET pouch for an intervertebral fusion device. The preparation method includes the following steps:

[0074] (a) Surface treatment:

[0075] The PET pouch was immersed in a hydrochloric acid solution with a pH value of 6.5 for 1.5 min, drained, rinsed, and dried. Then the PET pouch was placed in a plasma reaction chamber, and argon and oxygen were successively passed through a high-frequency electric field to generate plasma to impact the surface of the PET pouch. Among them, the pressure in the plasma reaction chamber was 0.5 Pa, and the power of the high-frequency electric field was 50 W; the argon introduction time was 10 s; the oxygen introduction time was 60 s to obtain a surface-treated PET pouch;

[0076] (b) Activation and introduction of linking molecules:

[0077] The surface-treated PET pouch was placed in an NHS solution with a concentration of 15 mmol / L and a pH value of 7.2 and ultrasonically treated at 40 °C for 20 s to obtain an activated PET pouch. Then the activated PET pouch was added to a PBS solution for stirring reaction to obtain a pretreated PET pouch. Among them, the pH value of the PBS solution was 6.3, the stirring reaction time was 30 s, and the stirring speed was 10 rpm;

[0078] (c) BMP immobilization:

[0079] The pretreated PET pouch and BMP were placed in an NHS solution and subjected to ultrasonic reaction to obtain a PET pouch with immobilized BMP. Among them, the concentration of the NHS solution was 15 mmol / L; the ultrasonic reaction time was 5 min; the final concentration of BMP was 6 mg / mL; the mass-volume ratio of the PET pouch to the NHS solution was 1:10;

[0080] (d) Stabilization and optimization:

[0081] The PET sachet for the intervertebral fusion device is obtained by placing the PET sachet with fixed BMP in PBS solution and performing heat treatment at 45 °C for 5 min.

[0082] Experimental examples

[0083] The PET sachets for the intervertebral fusion device are prepared according to the preparation methods of Example 3 and Comparative Examples 1-2 respectively;

[0084] The surface contact angles of the pretreated PET sachets obtained in step (b) are detected respectively, and the detection results are shown in Table 1;

[0085] The content of BMP protein (the remaining amount in the solution) in the remaining solution after ultrasonic reaction in step (c) is detected respectively, and the BMP loading rate of different preparation methods is calculated. The BMP loading rate = (BMP addition amount - remaining amount in the solution) / BMP addition amount × 100%; the calculation results are shown in Table 1;

[0086] Table 1

[0087] Group Contact angle BMP loading rate Example 3 79.35±21.4° 76.3％ Comparative Example 1 85.17±26.1° 52.8％ Comparative Example 2 82.61±18.7° 61.3％

[0088] As can be seen from Table 1:

[0089] Compared with the comparative examples, the PET sachet for the intervertebral fusion device prepared by the present invention can better load BMP, and thus can better improve the biological safety of the material and promote bone tissue regeneration.

[0090] Finally, it should be noted that the above embodiments are only used to illustrate the technical solutions of the present invention, rather than to limit them; although the present invention has been described in detail with reference to the foregoing embodiments, those of ordinary skill in the art should understand that they can still modify the technical solutions described in the foregoing embodiments, or perform equivalent replacements on some or all of the technical features; and these modifications or replacements do not make the essence of the corresponding technical solutions deviate from the scope of the technical solutions of the embodiments of the present invention, and they should all be covered by the scope of the claims and the description of the present invention.

Claims

1. A method for preparing a PET bag for an intervertebral fusion device, characterized in that: The preparation method comprises the following steps: (a) Surface treatment: The surface of the PET bag is treated with an acidic solution or an alkaline solution, and then the surface of the PET bag is treated with plasma to obtain a surface-treated PET bag; (b) Activation and introduction of linker molecules: The surface-treated PET capsule is placed in an NHS solution and subjected to ultrasonic treatment to obtain an activated PET capsule, and then the activated PET capsule and glycerol are added to a PBS solution for stirring reaction to obtain a pretreated PET capsule; (c) BMP fixation: The pretreated PET capsule and BMP are placed in an NHS solution and subjected to ultrasonic reaction to obtain a BMP-fixed PET capsule; (d) Stable optimization: The BMP-fixed PET capsule is placed in a PBS solution for heat treatment to obtain the intervertebral fusion cage PET capsule.

2. The preparation method according to claim 1, characterized in that: In the step (a), the acidic solution is a dilute hydrochloric acid solution; the alkaline solution is a sodium hydroxide solution or a potassium hydroxide solution; the pH value of the acidic solution is 6.2-6.6; the pH value of the alkaline solution is 7.5-8.0; and the treatment method is to soak the PET bag in the acidic solution or the alkaline solution for 1-2 minutes.

3. The preparation method according to claim 1, characterized in that: In the step (a), the plasma treatment of the surface of the PET bag comprises: placing the PET bag in a plasma reaction chamber, and then sequentially passing argon gas and oxygen gas through a high-frequency electric field to generate plasma to impact the surface of the PET bag.

4. The preparation method according to claim 3, characterized in that: The pressure in the plasma reaction chamber is 0.1-1 Pa, and the high-frequency electric field power is 10-100 W; The argon gas introduction time is 8 to 12 seconds; the oxygen introduction time is 50 to 70 seconds.

5. The preparation method according to claim 1, characterized in that: In the step (b), the concentration of the NHS solution is 12 to 18 mmol / L, the pH value is 7.1 to 7.5, the ultrasonic treatment temperature is 35 to 40° C., and the time is 15 to 25 seconds.

6. The preparation method according to claim 1, characterized in that: In the step (b), the pH value of the PBS solution is 6.2-6.5, the final concentration of glycerol added is 1%-3%, the stirring reaction time is 25-35s, and the stirring speed is 8-12rpm.

7. The preparation method according to claim 1, characterized in that: In the step (c), the concentration of the NHS solution is 12 to 18 mmol / L, and the ultrasonic time is 4 to 6 minutes.

8. The preparation method according to claim 1, characterized in that: In the step (c), the final concentration of BMP is 4-8 mg / mL; the mass volume ratio of the PET capsule to the NHS solution is 1:(8-12).

9. The preparation method according to claim 1, characterized in that: In the step (d), the heat treatment temperature is 40 to 50° C. and the time is 4 to 6 minutes.

10. The PET bag of intervertebral fusion cage prepared by the preparation method according to any one of claims 1 to 9.