Femtosecond laser-based implant with neck controllable hierarchical microporous structure and preparation method thereof

Abstract

The invention discloses a femtosecond laser-based implant with a neck controllable hierarchical microporous structure and a preparation method thereof, and relates to the technical field of dental implant preparation. According to the method, aiming at the neck area of the implant, the processing characteristics of high precision and low heat influence of femtosecond laser are utilized, and a graded micropore structure with controllable aperture size and spatial distribution is constructed in the neck area by regulating and controlling the laser scanning times; the graded microporous structure comprises at least two stages of micropores with different pore diameters and is used for realizing graded loading of functional particles or bioactive components. Compared with an existing dental implant surface treatment mode, on the premise that the overall mechanical property of the implant is not damaged, precise regulation and control over the surface appearance of the neck area are achieved, the hydrophilicity, biological activity and antibacterial and anti-inflammatory performance of the surface are remarkably improved, the soft and hard tissue interface environment is improved, and the long-term stability of the implant is improved.

Description

Technical Field

[0001] This invention relates to a dental implant with a controllable hierarchical microporous structure based on femtosecond laser and its preparation method, belonging to the field of dental implant preparation technology. Background Technology

[0002] The success of dental implants depends on the formation of a strong osseointegration with the jawbone. The implant neck region, adjacent to the gingival soft tissue, has a crucial impact on early soft tissue closure, prevention of microbial invasion, and long-term stability. Currently, mainstream implant surface treatment techniques (such as sandblasting, acid etching, and micro-arc oxidation) mostly create random, uniform, rough surfaces, which cannot achieve precise biomimetic matching with the microstructure of dense cortical bone and gingival connective tissue in the neck region. These homogenized surfaces struggle to simultaneously optimize the behavior of osteocytes and fibroblasts, and have limited functionality in antibacterial, anti-inflammatory, and active healing promotion.

[0003] Femtosecond laser processing technology, with its ultrashort pulses and extremely high peak power, enables ultra-precision, "cold" processing of metallic materials, providing a revolutionary tool for constructing microstructures with controllable morphology and size on implant surfaces. Therefore, this technology can be used to design and manufacture gradient, intelligent surfaces with excellent osseointegration, soft tissue sealing, and active biological functions, specifically tailored to the unique physiological environment of the implant neck. Summary of the Invention

[0004] The purpose of this invention is to overcome the shortcomings of the prior art and provide a femtosecond laser-based implant with a controllable hierarchical microporous structure in the neck and its preparation method. This method achieves a synergistic enhancement of the implant neck's bone integration and soft tissue sealing ability by precisely constructing multi-level micropores in the implant neck and selectively loading functionalized substances, thereby endowing it with long-lasting antibacterial, anti-inflammatory and healing-promoting functions.

[0005] In a first aspect, the present invention provides a method for preparing a cervical implant with a controllable hierarchical microporous structure based on a femtosecond laser, comprising the following steps: The outer surface of the implant neck is processed using a femtosecond laser to form a biomimetic microstructure composed of regularly arranged micropores, resulting in a femtosecond laser-treated implant. The femtosecond laser's parameters include wavelength 500-540 nm, pulse width 100-500 fs, repetition frequency 10-500 kHz, pulse energy 10-250 μJ, scanning speed 10-1000 mm / s, and scanning spacing 5-50 μm. The implant is chemically post-treated after femtosecond laser treatment to introduce functional particles or bioactive components onto the surface of the microstructure, resulting in an implant with a controllable hierarchical microporous structure in the neck based on femtosecond laser.

[0006] Furthermore, the implant is a pure titanium implant or a titanium alloy implant, and the titanium alloy implant includes Ti15Zr implants and Ti6Al4V implants.

[0007] Furthermore, before processing the outer surface of the implant neck with a femtosecond laser, the implant is pretreated. The pretreatment includes ultrasonically cleaning the implant at 60-80°C for 10-30 minutes and then drying it at 80-100°C for 30-50 minutes.

[0008] Furthermore, the process of using a femtosecond laser to process the outer surface of the implant neck includes: The neck of the implant is scanned for the first time using a femtosecond laser, which forms the first-level main micropores in the neck of the implant, resulting in the first scan-shaped structure. A femtosecond laser is used to perform a second scan on the structure formed in the first scan, which creates a second-level micropore in the neck of the implant, resulting in the structure formed in the second scan. A femtosecond laser is used to perform a third scan on the structure formed by the second scan, so that a third-level submicron structure is formed in the neck of the implant, resulting in the implant after femtosecond laser treatment; The average pore size of the first-level main micropore is 10~30μm, the average pore size of the second-level secondary micropore is 2~10μm, and the average pore size of the third-level submicron structure is 0.5~2μm.

[0009] Furthermore, the femtosecond laser condition parameters for the first scan include a pulse energy of 100~180μJ, a scanning speed of 100~300mm / s, and a scanning spacing of 20~30μm; The femtosecond laser conditions for the second scan include a pulse energy of 30-70 μJ, a scanning speed of 300-700 mm / s, and a scanning spacing of 8-15 μm. The femtosecond laser conditions for the third scan include a pulse energy of 10-30 μJ, a scanning speed of 700-1200 mm / s, and a scanning spacing of 3-8 μm.

[0010] Furthermore, the chemical post-treatment is a functionalized load, which is divided into primary load, secondary load and tertiary load.

[0011] Furthermore, the primary load includes: Prepare a cerium oxide suspension; The implants after femtosecond laser treatment are immersed in cerium oxide suspension and left to stand until the cerium oxide particles in the cerium oxide suspension completely fill the first-stage main micropores. After cooling, the implants are removed, cleaned, and dried to obtain the first-stage loaded implants. The secondary load includes: The primary loaded implant was immersed in a dispersion of polylactic acid-glycolic acid copolymer microspheres containing antibiotics and subjected to shaking treatment, so that the polylactic acid-glycolic acid copolymer microspheres containing antibiotics were selectively loaded into the secondary micropores. After washing and drying, the secondary loaded implant was obtained. The three-level load includes: The secondary loaded implant was immersed in a growth factor solution, allowing the growth factor to be adsorbed onto the tertiary submicron structure. The residual droplets on the surface were absorbed, and the implant was then freeze-dried under vacuum to obtain an implant with a controllable hierarchical microporous structure in the neck based on a femtosecond laser.

[0012] Furthermore, the concentration of the cerium oxide suspension is 10~50 mg / mL, and the particle size of the cerium oxide particles therein is in the range of 15~25 μm; The settling process includes placing the vessel in a Teflon-lined autoclave and treating it at 100-150°C for 1-3 hours. And / or, the antibiotic is at least one of minocycline and doxycycline; The concentration of antibiotic-containing polylactic acid-glycolic acid copolymer microspheres in the dispersion of antibiotic-containing polylactic acid-glycolic acid copolymer microspheres is 20~50 mg / mL; The polylactic acid-glycolic acid copolymer microspheres have an average particle size of 1.0~3.0 μm and a drug loading of 5~15 wt%. The oscillation treatment includes vibrating at a speed of 50-100 rpm for 4-8 hours within the range of 35-37°C; And / or, the growth factor is fibroblast growth factor-2; The concentration of the growth factor solution is 10~100 μg / mL; The soaking process involves immersing the secondary loaded implants in a growth factor solution at a temperature of 2–8°C for 2–6 hours under static, light-protected conditions.

[0013] Furthermore, the method for preparing the antibiotic-containing polylactic acid-glycolic acid copolymer microsphere dispersion includes: Dry polylactic acid-glycolic acid copolymer microspheres containing antibiotics were placed in a Tween-80 phosphate buffer solution and homogenized by ultrasonication, wherein the volume fraction of the Tween-80 phosphate buffer solution was 0.01~0.1%. And / or, the method for preparing the growth factor solution includes: The fibroblast growth factor-2 was obtained by adding phosphate buffer containing 0.1-1 wt% bovine serum albumin as a solvent. The pH range of the phosphate buffer solution is 7.2 to 7.4.

[0014] In a second aspect, the present invention also provides an implant with a controllable hierarchical microporous structure for the neck based on a femtosecond laser, which is prepared by the method for preparing an implant with a controllable hierarchical microporous structure for the neck based on a femtosecond laser as described in any one of the first aspects. The implant surface of the femtosecond laser-based controllable hierarchical microporous structure has a first-level main micropore, a second-level secondary micropore, and a third-level submicron structure. The first-level main micropore is loaded with large-particle-size sustained-release particles, the second-level secondary micropore is loaded with medium-particle-size controlled-release particles, and the third-level submicron structure is loaded with small-particle-size rapid-acting particles. The particle size range of the large-particle-size sustained-release particles is 10~30μm, the particle size range of the medium-particle-size controlled-release particles is 1.0~3.0μm, and the particle size range of the small-particle-size rapid-acting particles is 0.1~0.8μm.

[0015] Thirdly, the present invention also provides the application of the above-mentioned implant in the preparation of oral implantable medical devices for the restoration of missing or damaged teeth, and which have the functions of promoting osseointegration, accelerating soft tissue closure and anti-infection.

[0016] Compared with the prior art, the beneficial effects achieved by the present invention are as follows: This invention precisely loads three functional components—antioxidant / anti-inflammatory cerium oxide, antibiotics, and FGF-2, which promotes soft tissue healing—into porous structures of different sizes, achieving the orderly release and synergistic effect of these functional components. This composite surface possesses excellent hydrophilicity, high specific surface area, and bioactivity, significantly promoting protein adsorption, early cell adhesion and differentiation, enhancing the quality of soft tissue closure, and effectively reducing the risk of postoperative infection and inflammation. Attached Figure Description

[0017] Figure 1 This is a SEM image of the neck region of the implant in Embodiment 1 of the present invention; Figure 2 This is a SEM image of the neck region of the implant in Embodiment 2 of the present invention; Figure 3 This is a SEM diagram of the neck region of the implant in Embodiment 3 of the present invention. Detailed Implementation

[0018] The present invention will be further described below with reference to the accompanying drawings. The following embodiments are only used to more clearly illustrate the technical solution of the present invention, and should not be used to limit the scope of protection of the present invention. Example 1

[0019] This embodiment provides a method for preparing an implant with a first-level main micropore structure in the neck, including the following steps: (1) Implant pretreatment: Take pure titanium implants and place them in purified water at 70°C for ultrasonic cleaning for 20 minutes. Then, place the cleaned implants in a constant temperature oven at 90°C for drying for 40 minutes.

[0020] (2) Femtosecond laser processing: A femtosecond laser was used to scan the outer surface of the neck of the pretreated implant. The laser parameters were: wavelength 520 nm, pulse width 300 fs, repetition frequency 255 kHz, pulse energy 140 μJ, scanning speed 200 mm / s, and scanning spacing 25 μm. After processing, a regular microporous structure with an average pore size of approximately 20 μm was formed on the neck surface.

[0021] (3) Primary loading: Prepare an aqueous suspension of cerium oxide particles with a concentration of 30 mg / mL and a particle size of 20 μm. Completely immerse the implant treated in step (2) in this suspension and transfer it to a Teflon-lined autoclave. Let it stand at 125°C for 2 hours. After the reaction, remove the implant, ultrasonically clean it with purified water for 12.5 minutes at room temperature, and then dry it in a 70°C oven for 25 minutes to obtain an implant with a primary microporous structure at the neck. Figure 1 As can be seen, the neck surface treated by femtosecond laser exhibits a regular porous structure, and cerium oxide particles are uniformly loaded within these porous structures. Example 2

[0022] This embodiment provides a method for preparing an implant with a neck structure having a first-level main micropore and a second-level micropore structure, including the following steps: (1) Implant pretreatment: Same as step (1) in Example 1.

[0023] (2) Femtosecond laser processing: (2a) First scan: The outer surface of the implant neck is scanned for the first time using a femtosecond laser. The laser parameters are the same as in step (2) of Example 1.

[0024] (2b) Second scan: In the same area where step (2a) was completed, a second scan was performed using a femtosecond laser. The laser parameters were: wavelength 520 nm, pulse width 300 fs, repetition rate 255 kHz, pulse energy 50 μJ, scan speed 500 mm / s, and scan spacing 11.5 μm. After processing, a bilevel structure containing a first-level primary micropore (average pore size approximately 20 μm) and a second-level secondary micropore (average pore size approximately 6 μm) was formed on the neck surface.

[0025] (3) Level 1 load: The operation is the same as step (3) in Example 1.

[0026] (4) Secondary loading: The implant obtained in step (3) was immersed in a drug-loaded PLGA microsphere dispersion. The concentration of PLGA microspheres in the dispersion was 35 mg / mL, the average particle size of the PLGA microspheres was 2.0 μm, the drug loading was 10% (w / w), the loaded antibiotic was minocycline, and the dispersion medium was PBS buffer (pH 7.3) containing 0.055% (v / v) Tween-80. The immersion conditions were: 36℃, shaking at 75 rpm for 6 hours. After immersion, the implant surface was rinsed with PBS buffer and dried at 70℃ to obtain an implant with a primary micropore and secondary micropore structure at the neck. Figure 2 As can be seen, after the femtosecond laser scanning, a submicroporous structure has been formed on the surface, with an average pore size of 6μm. Example 3

[0027] This embodiment provides a method for preparing a cervical implant with a controllable hierarchical microporous structure based on femtosecond laser, including the following steps: (1) Implant pretreatment: Same as step (1) in Example 1.

[0028] (2) Femtosecond laser processing: (2a) First scan: Same as step (2a) in Example 2.

[0029] (2b) Second scan: Same as step (2b) in Example 2.

[0030] (2c) Third scan: In the same area where step (2b) was completed, a third scan was performed using a femtosecond laser. The laser parameters were: wavelength 520 nm, pulse width 300 fs, repetition rate 255 kHz, pulse energy 20 μJ, scan speed 950 mm / s, and scan spacing 5.5 μm. After processing, a multi-level structure was formed on the neck surface, including a first-level main micropore, a second-level secondary micropore, and a third-level submicron structure (average pore size of approximately 1.25 μm).

[0031] (3) Level 1 load: The operation is the same as step (3) in Example 1.

[0032] (4) Secondary load: The operation is the same as step (4) in Example 2.

[0033] (5) Tertiary loading: The implant obtained in step (4) was immersed in a fibroblast growth factor-2 solution. The solution was a PBS buffer (pH 7.3) containing 0.55% (w / v) bovine serum albumin, with a recombinant human fibroblast growth factor-2 concentration of 55 μg / mL. The immersion conditions were: static immersion at 5°C in the dark for 4 hours. After immersion, the surface droplets were blotted dry with sterile filter paper, followed by vacuum freeze-drying to obtain an implant with a femtosecond laser-based controllable hierarchical microporous structure in the neck region. Figure 3 It can be seen that after the third femtosecond laser scan, a submicron-scale pore structure was formed on the surface of the implant neck.

[0034] Comparative Example 1: The difference between this comparative example and Example 1 is that no subsequent processing was performed.

[0035] Comparative Example 2: The surface treatment method used in this comparative example is SLA, which is commonly used in commercially available implants. The specific steps are as follows: Take pure titanium implants and ultrasonically clean them in purified water at 70℃ for 20 minutes. Place the cleaned implants in a constant temperature oven at 90℃ for 40 minutes before use.

[0036] The cleaned implants were then sandblasted using Al2O3 abrasive with a particle size of 300μm. The nozzle-to-product distance was adjusted to 25mm, and the sandblasting time was 15s. The sandblasting pressure for the neck, body, and roots was 3.5bar.

[0037] A mixed aqueous solution consisting of 35.8% sulfuric acid and 8.75% hydrochloric acid (by volume) was prepared, heated to 80°C and held for 5 minutes, and then the implants were placed in the solution for reaction for 30 minutes. After acid etching, the implants were ultrasonically cleaned in purified water at 80°C for 30 minutes. They were then dried in an oven at 80°C for 30 minutes.

[0038] The contact angle of Examples 1-3 and Comparative Examples 1-2 was tested below. The test method is as follows: Using a contact angle measuring instrument, a drop of deionized water (about 2-5 µL) was dropped onto the surface of the sample to be tested using the seat drop method. The side profile image was photographed, and the static contact angle was obtained by software fitting analysis. Five samples were tested for each example and comparative example. The neck of each sample was measured. The results are shown in Table 1.

[0039] Table 1: Contact angle test results of Examples 1-3 and Comparative Examples 1-2

[0040] Test results show that the technical solution of this invention has a systematic advantage in improving the wettability of the implant neck surface. The smooth titanium surface of Comparative Example 1 exhibits typical hydrophobic properties (94°), while the contact angle of Comparative Example 2, after conventional sandblasting and acid etching treatment, decreased to 72°, showing limited improvement from roughness, but still within the hydrophobic range. In contrast, all embodiments of this invention achieve a significant improvement in hydrophilicity: the single-level micropores combined with cerium oxide filling in Example 1 reduced the contact angle to 26°, achieving a hydrophilic state; Example 2, by introducing a second-level micropore and PLGA loading, further increased the contact angle to 13°; and Example 3 had a contact angle of 4°.

[0041] The decreasing contact angle trend indicates that the porous surface structure and functionalization treatment can effectively improve the wettability of the material. The superhydrophilic state achieved in Example 3 is mainly due to the capillary action generated by the micro-nano composite structure and the hydrophilic groups introduced by surface modification. This surface property helps the implant to be wetted by tissue fluid more quickly in vivo, thus providing favorable conditions for subsequent protein adsorption and cell attachment, which is of positive significance for the early stability of the implant.

[0042] The implant surface of the femtosecond laser-based controllable hierarchical microporous structure for the neck provided by this invention has a first-level main micropore, a second-level secondary micropore, and a third-level submicron structure. The first-level main micropore, the second-level secondary micropore, and the third-level submicron structure are respectively loaded with functional particles of different particle size ranges. These functional particles include large-particle-size sustained-release particles, medium-particle-size controlled-release particles, and small-particle-size rapid-acting particles, to achieve a staged, sequential, sustained-release targeted effect. Specifically: The first-stage main micropores are loaded with large-particle sustained-release particles with a particle size range of 10~30μm, the second-stage secondary micropores are loaded with medium-particle controlled-release particles with a particle size range of 10~30μm, and the third-stage submicron structure is loaded with small-particle fast-acting particles with a particle size range of 0.1~0.8μm.

[0043] The ingredients of large-particle-size sustained-release granules, medium-particle-size controlled-release granules, and small-particle-size fast-acting granules can be the same or different. Large-particle-size sustained-release granules are used for long-term sustained release and long-term antibacterial effects, medium-particle-size controlled-release granules are used for medium-term controlled release and bone integration promotion, and small-particle-size fast-acting granules are used for medium-term controlled release and bone integration promotion.

[0044] Functional particles include, but are not limited to, one or more of the following: oxides, ceramic particles, drug-loaded microspheres, bioactive glass, metal-organic framework materials, protein factor complexes, or bioactive peptide nanoparticles. Particle carriers include, but are not limited to, polylactic-co-glycolic acid copolymer (PLGA), polycaprolactone (PCL), chitosan, hyaluronic acid, peptide gels, mesoporous silica (MSN), and surface-modified nanoparticles rich in carboxyl or amino groups.

[0045] This invention utilizes the synergistic effect of a functional particle system with ordered size distribution and the morphology of the neck microstructure to achieve the temporal release of different biological functions.

[0046] The above description is only a preferred embodiment of the present invention. It should be noted that for those skilled in the art, several improvements and modifications can be made without departing from the technical principles of the present invention, and these improvements and modifications should also be considered within the scope of protection of the present invention.

Claims

1. A method for preparing a cervical implant with a controllable hierarchical microporous structure based on femtosecond laser, characterized in that, Includes the following steps: The outer surface of the implant neck is processed using a femtosecond laser to form a biomimetic microstructure composed of regularly arranged micropores, resulting in a femtosecond laser-treated implant. The femtosecond laser's parameters include wavelength 500-540 nm, pulse width 100-500 fs, repetition frequency 10-500 kHz, pulse energy 10-250 μJ, scanning speed 10-1000 mm / s, and scanning spacing 5-50 μm. The implant is chemically post-treated after femtosecond laser treatment to introduce functional particles or bioactive components onto the surface of the microstructure, resulting in an implant with a controllable hierarchical microporous structure in the neck based on femtosecond laser.

2. The method for preparing a cervical implant with a controllable hierarchical microporous structure based on femtosecond laser according to claim 1, characterized in that, The implant is a pure titanium implant or a titanium alloy implant, and the titanium alloy implant includes Ti15Zr implants and Ti6Al4V implants.

3. The method for preparing a cervical implant with a controllable hierarchical microporous structure based on a femtosecond laser according to claim 1, characterized in that, Before processing the outer surface of the implant neck with a femtosecond laser, the implant is pretreated, which includes ultrasonically cleaning the implant at 60-80°C for 10-30 minutes and then drying it at 80-100°C for 30-50 minutes.

4. The method for preparing a cervical implant with a controllable hierarchical microporous structure based on a femtosecond laser according to claim 1, characterized in that, The process of using a femtosecond laser to process the outer surface of the implant neck includes: The neck of the implant is scanned for the first time using a femtosecond laser, which forms the first-level main micropores in the neck of the implant, resulting in the first scan-shaped structure. A femtosecond laser is used to perform a second scan on the structure formed in the first scan, which creates a second-level micropore in the neck of the implant, resulting in the structure formed in the second scan. A femtosecond laser is used to perform a third scan on the structure formed by the second scan, so that a third-level submicron structure is formed in the neck of the implant, resulting in the implant after femtosecond laser treatment; The average pore size of the first-level main micropore is 10~30μm, the average pore size of the second-level secondary micropore is 2~10μm, and the average pore size of the third-level submicron structure is 0.5~2μm.

5. The method for preparing an implant with a controllable hierarchical microporous structure based on a femtosecond laser in the neck according to claim 4, characterized in that, The femtosecond laser condition parameters for the first scan include a pulse energy of 100~180μJ, a scanning speed of 100~300mm / s, and a scanning spacing of 20~30μm; The femtosecond laser conditions for the second scan include a pulse energy of 30-70 μJ, a scanning speed of 300-700 mm / s, and a scanning spacing of 8-15 μm. The femtosecond laser conditions for the third scan include a pulse energy of 10-30 μJ, a scanning speed of 700-1200 mm / s, and a scanning spacing of 3-8 μm.

6. The method for preparing a cervical implant with a controllable hierarchical microporous structure based on a femtosecond laser according to claim 1, characterized in that, The chemical post-treatment is a functionalized load, which is divided into primary load, secondary load and tertiary load.

7. The method for preparing a cervical implant with a controllable hierarchical microporous structure based on a femtosecond laser according to claim 6, characterized in that, The primary load includes: Prepare a cerium oxide suspension; The implants after femtosecond laser treatment are immersed in cerium oxide suspension and left to stand until the cerium oxide particles in the cerium oxide suspension completely fill the first-stage main micropores. After cooling, the implants are removed, cleaned, and dried to obtain the first-stage loaded implants. The secondary load includes: The primary loaded implant was immersed in a dispersion of polylactic acid-glycolic acid copolymer microspheres containing antibiotics and subjected to shaking treatment, so that the polylactic acid-glycolic acid copolymer microspheres containing antibiotics were selectively loaded into the secondary micropores. After washing and drying, the secondary loaded implant was obtained. The three-level load includes: The secondary loaded implant was immersed in a growth factor solution, allowing the growth factor to be adsorbed onto the tertiary submicron structure. The residual droplets on the surface were absorbed, and the implant was then freeze-dried under vacuum to obtain an implant with a controllable hierarchical microporous structure in the neck based on a femtosecond laser.

8. The method for preparing an implant with a controllable hierarchical microporous structure based on a femtosecond laser in the neck according to claim 7, characterized in that, The concentration of the cerium oxide suspension is 10~50 mg / mL, and the particle size of the cerium oxide particles therein is 15~25 μm; The settling process includes placing the vessel in a Teflon-lined autoclave and treating it at 100-150°C for 1-3 hours. And / or, the antibiotic is at least one of minocycline and doxycycline; The concentration of antibiotic-containing polylactic acid-glycolic acid copolymer microspheres in the dispersion of antibiotic-containing polylactic acid-glycolic acid copolymer microspheres is 20~50 mg / mL; The polylactic acid-glycolic acid copolymer microspheres have an average particle size of 1.0~3.0 μm and a drug loading of 5~15 wt%. The oscillation treatment includes vibrating at a speed of 50-100 rpm for 4-8 hours within the range of 35-37°C; And / or, the growth factor is fibroblast growth factor-2; The concentration of the growth factor solution is 10~100 μg / mL; The soaking process involves immersing the secondary loaded implants in a growth factor solution at a temperature of 2–8°C for 2–6 hours under static, light-protected conditions.

9. The method for preparing an implant with a controllable hierarchical microporous structure based on a femtosecond laser according to claim 7, characterized in that, The preparation method of the antibiotic-containing polylactic acid-glycolic acid copolymer microsphere dispersion includes: Dry polylactic acid-glycolic acid copolymer microspheres containing antibiotics were placed in a Tween-80 phosphate buffer solution and homogenized by ultrasonication, wherein the volume fraction of the Tween-80 phosphate buffer solution was 0.01~0.1%. And / or, the method for preparing the growth factor solution includes: The fibroblast growth factor-2 was obtained by adding phosphate buffer containing 0.1-1 wt% bovine serum albumin as a solvent. The pH range of the phosphate buffer solution is 7.2 to 7.

4.

10. A cervical implant with a controllable hierarchical microporous structure based on femtosecond laser, characterized in that, The implant was prepared by the method for preparing a femtosecond laser-based cervical controllable hierarchical microporous structure as described in any one of claims 1 to 9. The implant surface of the femtosecond laser-based controllable hierarchical microporous structure has a first-level main micropore, a second-level secondary micropore, and a third-level submicron structure. The first-level main micropore is loaded with large-particle-size sustained-release particles, the second-level secondary micropore is loaded with medium-particle-size controlled-release particles, and the third-level submicron structure is loaded with small-particle-size rapid-acting particles. The particle size range of the large-particle-size sustained-release particles is 10~30μm, the particle size range of the medium-particle-size controlled-release particles is 1.0~3.0μm, and the particle size range of the small-particle-size rapid-acting particles is 0.1~0.8μm.

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