A self-expanding occlusive implant for annular disc defects and method of making same

Abstract

The application discloses a self-expanding blocking implant for annulus fibrosus defect of intervertebral disc and a preparation method thereof, and belongs to the technical field of biomedical materials. The implant is a solid porous body with a preformed three-dimensional shape in a dry state, and has an axisymmetric dumbbell structure as a whole, sequentially comprising an outer blocking section, a middle connecting body and an inner abutting section along the axial direction. The middle connecting body is in a cylindrical shape, and the outer blocking section and the inner abutting section abut on the outer wall and the inner wall of the annulus fibrosus respectively, forming a bidirectional clamping anti-extrusion limiting. The implant prepared by the application is delivered in the form of a solid dry body, and only needs to be placed in the defect during clinical implantation operation, without liquid injection, light curing or other energy input throughout the process, so that the surgical steps are greatly simplified, the operation time is shortened, the risk of operation failure is reduced, the learning curve is gentle, and the implant is suitable for in-surgery popularization and application.

Description

Technical Field

[0001] This invention belongs to the field of biomedical materials technology, specifically relating to a self-expanding occlusion implant for intervertebral disc annulus fibrosus defects and its preparation method. Background Technology

[0002] Lumbar disc herniation is a common clinical condition. Its main pathological mechanism involves the protrusion of the nucleus pulposus after the annulus fibrosus ruptures, compressing adjacent spinal nerve roots and causing symptoms such as lower back and leg pain and numbness. Minimally invasive decompression procedures such as percutaneous transforaminal endoscopic discectomy (PTED) and percutaneous endoscopic lumbar discectomy can effectively remove the herniated nucleus pulposus and relieve nerve compression. However, these procedures all require creating a surgical defect (usually no less than 4 mm) in the annulus fibrosus. Due to the extremely limited self-repair capacity of the annulus fibrosus, the re-protrusion rate of the nucleus pulposus is as high as 2% to 25%, with approximately 80% of re-protrusion occurring at the original surgical defect site. This poses a serious risk of secondary injury to patients and has become a major limiting factor in the long-term efficacy of minimally invasive disc surgery.

[0003] Existing methods for treating annulus fibrosus defects mainly fall into the following categories, all of which have significant shortcomings:

[0004] Category 1: Suture repair. For ruptures smaller than 4 mm, suturing can be used to close them. However, for surgical defects of 4 mm or more, suturing is not feasible under minimally invasive channels, and the tension after suturing is uneven, so the long-term maintenance effect is uncertain.

[0005] The second type is mechanical occluders, represented by the American Barricaid system. These occluders use a composite structure of polyester fiber mesh and titanium alloy bone anchors. Clinical follow-up over 5 years shows that they can reduce the risk of re-protrusion by about 15% to 20%. However, they carry the risk of serious complications such as endplate lesions, device migration and dislocation, bone anchor breakage, and foreign body reaction. In addition, they require additional manipulation of the vertebral body, which is highly invasive and not suitable for patients with osteoporosis.

[0006] The third type is injectable in-situ curing gel. A liquid gel precursor is injected into the defect via a delivery device, and in-situ curing is achieved through light, temperature, or chemical triggering. This method has the following main drawbacks: there is a risk of leakage of the liquid precursor during injection, which may trigger inflammatory reactions in surrounding tissues; the quality of in-situ curing is affected by factors such as surgical field lighting conditions and temperature uniformity, resulting in poor batch-to-batch consistency; the shape of the cured product is difficult to control precisely, and its fit to the defect contour is unstable; the delivery system is complex, with many steps and a long operation time.

[0007] The fourth category is pouch-filled devices, such as the solution disclosed in Chinese invention patent application CN119564383A. This involves a prefabricated biodegradable elastic pouch, incorporating liquid filler injected intraoperatively through a drainage channel, followed by curing via a trigger (light exposure). While this solution addresses some positioning issues, it still relies on the two-step process of intraoperative liquid injection and external light curing, failing to fundamentally resolve operational complexity. Furthermore, the long-term stability of the interface between the pouch and the filler poses a potential risk, and the product structure is relatively complex. The pouch structure also suffers from stress concentration at the interface between the pouch wall and the internal filler, making it prone to delamination or wall rupture under long-term dynamic loads on the spine, leading to occlusion failure.

[0008] Furthermore, all four existing solutions mentioned above aim solely at "physical blockage," failing to address the fundamental pathological problem of insufficient self-regenerative and repair capabilities of the annulus fibrosus tissue.

[0009] Therefore, the present invention provides a self-expanding occlusion implant for intervertebral disc annulus fibrosus defects and its preparation method, which solves the technical problem that the existing technology lacks annulus fibrosus that can be easily operated under minimally invasive channels, does not require intraoperative fluid injection or external energy triggering, can autonomously conform to the defect shape after implantation, provides continuous mechanical support, and is eventually completely degraded and absorbed. Summary of the Invention

[0010] The purpose of this invention is to provide a self-expanding occlusion implant for intervertebral disc annulus fibrosus defects and its preparation method, in order to solve the technical problem that the prior art lacks a simple operation under minimally invasive channels, does not require intraoperative fluid injection or external energy triggering, and achieves adaptive occlusion by self-absorbing tissue fluid swelling.

[0011] To achieve the above objectives, the present invention adopts the following technical solution:

[0012] A self-expanding occlusion implant for intervertebral disc annulus fibrosus defects, wherein the implant, in a dry state, is a solid porous body with a pre-formed three-dimensional shape, the solid porous body being adapted to the anatomical morphology of the annulus fibrosus defect site; the implant as a whole has an axisymmetric dumbbell-shaped structure, comprising, along its axial direction, an outer occlusion segment, a middle connector, and an inner abutment segment; wherein the cross-sectional area of ​​the middle connector is smaller than the cross-sectional areas of the outer occlusion segment and the inner abutment segment; the implant has an open communicating pore structure inside, and the implant is composed of a multi-network polymer material consisting of at least two cross-linked networks, having a first network and a second network.

[0013] Furthermore, the pore size of the connecting holes is 10 to 500 micrometers. This connecting hole structure provides a channel for tissue fluid infiltration into the implant, enabling the implant to rapidly absorb surrounding tissue fluid and reach swelling equilibrium, meeting the acceptable waiting time requirements during clinical procedures. The aforementioned connecting hole structure is prepared using a freeze-drying process, with the specific freezing procedure parameters determining the pore size distribution.

[0014] Preferably, the aperture of the connecting hole is 50 to 300 micrometers.

[0015] Furthermore, the mid-section connector is the main body of the implant, and is cylindrical. The diameter D of the mid-section connector is 4 to 6 mm, where the diameter D is an integer. The axial length L of the mid-section connector is 8 to 12 mm, where the axial length L is an integer. The diameter D of the mid-section connector is adapted to the diameter of the implanted annulus fibrosus defect, and the length L is adapted to the thickness of the annulus fibrosus.

[0016] Furthermore, the lateral occlusion segment is located at the outer end of the middle connector, that is, the end located on the outer side of the annulus fibrosus and adjacent to the spinal canal after implantation. It is disc-shaped with a diameter of D+1 mm and an axial thickness of 1 mm. After implantation, the lateral occlusion segment abuts against the outer wall of the annulus fibrosus, providing an outward anti-dislodgement limiting function.

[0017] Furthermore, the inner abutment segment is located at the inner end of the mid-segment connector, that is, the end located inside the annulus fibrosus and adjacent to the nucleus pulposus after implantation. It consists of two axially adjacent parts, a and b. Part a is a cylindrical base, coaxial with the mid-segment connector, with a diameter of D+2 mm and an axial thickness of 2 mm. Part b is a spherical cap, coaxial with part a and located above the inner end face of part a. The circumference of its bottom surface coincides with the circumference of the end face of part a, that is, the radius of its bottom surface is equal to (D+2 mm). The central angle of the spherical crown, i.e., the central angle of the sphere, is 20-40°. The height and radius of curvature of the spherical crown are uniquely determined by the base radius and the central angle. The inner abutment segment is located in the inner cavity of the annulus fibrosus after implantation. After swelling, it abuts against the inner wall of the annulus fibrosus and works with the outer sealing segment to form a bidirectional clamping effect on the inner and outer walls of the annulus fibrosus, providing a function of preventing dislodgement and limiting the position. No additional fixation mechanism is required, and no additional operation or damage is caused to the vertebral bone.

[0018] Furthermore, during implantation, the mid-section connector passes through the defective channel of the annulus fibrosus; after implantation, the outer blocking segment and the inner abutting segment abut against the outer and inner walls of the annulus fibrosus respectively under the elasticity of the material itself and the swelling effect driven by tissue fluid.

[0019] The present invention also provides a method for preparing the above-mentioned implant, which can be implemented through two preferred schemes:

[0020] M1, a dual-network system of polyethylene glycol / sodium alginate, is constructed by amino-succinimide ester reaction and ionic crosslinking. The first network is formed by covalent crosslinking of four-arm polyethylene glycol succinimide glutarate with an amine crosslinking agent, and the second network is formed by ionic crosslinking of sodium alginate with divalent calcium ions.

[0021] M2, a photocrosslinking system of hyaluronic acid methacrylate / o-nitrobenzyl glycol, constructs an interpenetrating network through UV-initiated free radical polymerization. The first and second networks are formed together through photo-initiated free radical polymerization and mercapto-olefin click chemistry.

[0022] Furthermore, the polyethylene glycol / sodium alginate dual-network system in M1 also contains hydroxyapatite (HAP), which is uniformly dispersed in the dual-network matrix as an inorganic reinforcing phase.

[0023] A method for preparing a self-expanding occlusion implant for intervertebral disc annulus fibrosus defects, wherein the polyethylene glycol / sodium alginate dual-network system in M1 specifically includes the following steps:

[0024] S1. Dissolve four-arm polyethylene glycol succinimide glutarate (4arm-PEG-SG), sodium alginate, and hydroxyapatite (HAP) together in phosphate buffer (PBS) and stir at 4°C until completely clear to obtain component A; dissolve the amine crosslinking agent in borate buffer to obtain component B;

[0025] S2. Mix components A and B in a volume ratio of 1:1 and immediately inject the mixture into a pre-shaped mold. Let it stand at room temperature to crosslink and obtain a wet gel, i.e., the first network.

[0026] S3. Remove the wet gel from the mold and immerse it in CaCl2 solution at room temperature to allow calcium ions to penetrate into the gel and crosslink with the carboxyl groups on the sodium alginate chain to form a second network.

[0027] S4. Rinse the wet gel soaked in step S3 with PBS to remove residual calcium ions from the surface, then freeze-dry to obtain a white porous solid dried body, sterilize it, and obtain implant 1.

[0028] Further, in S1, the molecular weight of the four-arm polyethylene glycol succinimide glutarate is 10 kDa or 20 kDa; the ratio of the four-arm polyethylene glycol succinimide glutarate, sodium alginate, hydroxyapatite, and phosphate buffer is 100 mg: (3-5) mg: (100-200) mg: 5 mL; the pH of the borate buffer is 8.2, and the pH of the phosphate buffer is 7.2-7.4;

[0029] Further, in S1, the amine crosslinking agent is one or both of ε-polylysine hydrochloride and trilysine; the ratio of the amine crosslinking agent to the borate buffer is 36 mg: 5 mL;

[0030] Preferably, the soaking time at room temperature in S3 is 60 min, the concentration of CaCl2 solution is 200 mmol / L, and the drying is either freeze-drying or air-drying. The freeze-drying is performed by cooling the temperature at a rate of 1℃ / min to -40℃ to -80℃, holding the temperature for at least 2 hours, and then sublimating the temperature under a vacuum of ≤10 Pa. The air-drying is performed by air-drying in an oven at 37℃ overnight to obtain a white porous solid dried body.

[0031] Preferably, the molecular weight of the four-armed polyethylene glycol succinimide glutarate is 10 kDa or 20 kDa; the molecular weight of the ε-polylysine hydrochloride is 2-5 kDa; and the viscosity of the sodium alginate is 150 mPa·s.

[0032] Furthermore, in S2, the NHS groups of the four-arm polyethylene glycol succinimide glutarate covalently crosslink with the primary amino groups of the amine crosslinking agent; wherein, the four-arm polyethylene glycol succinimide glutarate serves as a covalent backbone precursor; the amine crosslinking agent and the four-arm polyethylene glycol succinimide glutarate rapidly construct the first network through an aminosuccinimide ester reaction; sodium alginate and divalent calcium ions in the calcium chloride solution form a reversible ionic crosslinking network to construct the second network.

[0033] A method for preparing a self-expanding occlusion implant for intervertebral disc annulus fibrosus defects, wherein the M2 contains a hyaluronic acid methacrylate / o-nitrobenzyl alcohol-modified polyethylene glycol photocrosslinking system, specifically comprising the following steps:

[0034] Q1. Dissolve hyaluronic acid methacrylate (HAMA) powder in pre-cooled phosphate buffer and place it in a refrigerator at 0-4℃ overnight to completely dissolve it, thus obtaining HAMA stock solution; dissolve multi-arm o-nitrobenzyl alcohol-modified polyethylene glycol (PEG-NB) powder in pre-cooled phosphate buffer and mix it by shaking under light-protected conditions, thus obtaining PEG-NB stock solution.

[0035] Q2. Mix the HAMA mother liquor and PEG-NB mother liquor, add the photoinitiator, and obtain a mixed solution;

[0036] Q3. Inject the mixed solution into a pre-shaped mold and cure it under ultraviolet light to cause the methacrylate groups in hyaluronic acid methacrylate (HAMA) to undergo free radical polymerization. At the same time, multi-arm o-nitrobenzyl alcohol polyethylene glycol (PEG-NB) participates in cross-linking through mercapto-olefin click chemistry to form a hydrogel. Dry the hydrogel and sterilize it to obtain implant 2.

[0037] Furthermore, the temperature of the pre-cooled phosphate buffer in Q1 is 0-4°C, the pH of the phosphate buffer is 7.4, the molecular weight of the hyaluronic acid methacrylate in Q1 is 40 kDa, and the grafting degree of the hyaluronic acid methacrylate is 85% to 95%.

[0038] Furthermore, the photoinitiator in Q2 is lithium phenyl (2,4,6-trimethylbenzoyl)phosphate (LAP).

[0039] Furthermore, the concentrations of HAMA mother liquor, PEG-NB mother liquor and photoinitiator mother liquor in the mixed solution in Q2 are (6.7wt%-9wt%), (20wt%-45wt%) and (0.5wt%-1wt%), respectively.

[0040] Furthermore, the volume ratio of HAMA mother liquor and PEG-NB mother liquor in the mixed solution in Q2 is (1-2):(3-5).

[0041] Preferably, the concentrations of HAMA mother liquor, PEG-NB mother liquor and photoinitiator in the mixed solution in Q2 are 6.7wt%, 20wt% and 0.8wt%, respectively; the volume ratio of HAMA mother liquor to PEG-NB mother liquor is 1:3.

[0042] Furthermore, in Q3, UV curing involves irradiating both sides of the mold for 300 seconds each under UV light with a wavelength of 365 nm, with an UV light intensity of 280-320 milliwatts per square centimeter; drying is one of freeze drying and air drying, wherein freeze drying involves cooling to -40°C to -80°C at a programmed rate of 1°C / min, holding at that temperature for at least 2 hours, and then sublimating under a vacuum of ≤10 Pa; air drying is done overnight in an oven at 37°C.

[0043] In summary, due to the adoption of the above technical solution, the beneficial effects of the present invention are:

[0044] 1. The implant of this invention is delivered in solid, dry form. Clinical implantation only requires placing the implant into the defect site, eliminating the need for liquid injection, light curing, or other energy input. This significantly simplifies the surgical procedure, shortens the operation time, reduces the risk of operational errors, and is easy to perform without additional intraoperative intervention. The implant's porous internal structure allows for rapid liquid absorption and swelling, with pre-forming followed by swelling, eliminating the uncertainty of intraoperative curing. The swelling process itself is a volume expansion process, generating active expansion pressure on the defect edges. The resulting mechanical action applies uniform adhesion pressure to the annulus fibrosus tissue at the defect edges, effectively closing micro-cracks and preventing re-protrusion of the nucleus pulposus. Furthermore, it forms a dynamic mechanical anchoring effect, enhancing the interfacial stability between the implant and host tissue, preventing displacement or extrusion. In addition, it can simulate the circumferential tension of the natural annulus fibrosus, providing immediate mechanical support in the early stages of repair, maintaining intervertebral disc height and spinal segment stability, thereby improving the reliability, sealing durability, and biomechanical compatibility of annulus fibrosus defect closure.

[0045] 2. This invention utilizes a polyethylene glycol / sodium alginate dual-network system, in which high molecular weight PEG forms irreversible amide bond crosslinks with ε-polylysine / trilysine, providing a high-strength framework; sodium alginate forms ionic crosslinks with calcium ions, exhibiting energy dissipation capabilities. Under external force, the ionic bonds can break and recombine, absorbing impact energy and preventing brittle fracture; furthermore, HAP, as a natural bone mineral component, significantly enhances mechanical properties.

[0046] 3. This invention utilizes a photocrosslinking system of hyaluronic acid methacrylate / o-nitrobenzyl alcohol-modified polyethylene glycol. In this system, the methacrylate groups undergo free radical polymerization to form a rigid hyaluronic acid backbone network, providing bioadhesion and compressive strength. The o-nitrobenzyl alcohol generates active thiol groups under UV light, which undergo a highly efficient and orthogonal thiol-alkene click reaction with the double bonds of HAMA to form a second network. The two networks are entangled at the molecular scale without phase separation, synergistically enhancing the energy storage modulus. Furthermore, the structure remains intact after swelling, making it less prone to breakage and preventing implant collapse or extrusion. Attached Figure Description

[0047] The present invention will be further described below with reference to the accompanying drawings and embodiments.

[0048] Figure 1 This is a three-dimensional structural schematic diagram of the self-expanding occlusion implant for intervertebral disc annulus fibrosus defects according to the present invention;

[0049] Figure 2 This is a front view of the self-expanding occlusion implant for intervertebral disc annulus fibrosus defects according to the present invention;

[0050] Among them, 1 is the outer blocking section, 2 is the middle connecting body, 3 is the inner abutting section, 4 is part a, and 5 is part b. Detailed Implementation

[0051] The technical solutions in the embodiments of the present invention will be clearly and completely described below. Obviously, the described embodiments are only some embodiments of the present invention, and not all embodiments. Based on the embodiments of the present invention, all other embodiments obtained by those skilled in the art without creative effort are within the scope of protection of the present invention.

[0052] Example 1:

[0053] like Figure 1 As shown, this embodiment discloses a self-expanding occlusion implant for intervertebral disc annulus fibrosus defects. The implant, in its dry state, is a solid porous body with a pre-formed three-dimensional shape, which is adapted to the anatomical morphology of the annulus fibrosus defect site. The implant has an axially symmetrical dumbbell-shaped structure, which includes an outer occlusion segment 1, a middle connector 2, and an inner abutment segment 3 along its axial direction. The implant has an open and interconnected pore structure inside, and is composed of a multi-network polymer material consisting of at least two cross-linked networks, having a first network and a second network.

[0054] The pores inside the implant have a diameter of 100 micrometers. The pore structure provides a channel for tissue fluid to flow into the implant, enabling the implant to quickly absorb surrounding tissue fluid.

[0055] During implantation, the mid-section connector passes through the defective channel of the annulus fibrosus; after implantation, the outer sealing section and the inner abutting section abut against the outer and inner walls of the annulus fibrosus respectively under the elasticity of the material itself and the swelling driven by tissue fluid.

[0056] The mid-section connector 2 is the main body of the implant, and is cylindrical. The diameter D of the mid-section connector is 5 mm; the axial length L of the mid-section connector is 10 mm; the diameter D of the mid-section connector is adapted to the diameter of the implanted annulus fibrosus defect, and the length L is adapted to the thickness of the annulus fibrosus.

[0057] The outer sealing segment 1 is located at the outer end of the middle connector 2, that is, after implantation, it is located on the outer side of the annulus fibrosus and adjacent to the spinal canal. It is disc-shaped with a diameter of 6 mm and an axial thickness of 1 mm. After implantation, the outer sealing segment 1 abuts against the outer wall of the annulus fibrosus, providing an outward anti-dislodgement limiting function.

[0058] The inner abutment segment 3 is located at the inner end of the middle connector 2, that is, the end located inside the annulus fibrosus and adjacent to the nucleus pulposus after implantation. It consists of axially adjacent parts a 4 and b 5. Part a is a cylindrical base, coaxial with the middle connector, with a diameter of 7 mm and an axial thickness of 2 mm. Part b is a spherical crown, coaxial with part a and located on the inner end face of part a. Its bottom circumference coincides with the end face circumference of part a, that is, the bottom radius is equal to 3.5 mm. The central angle corresponding to the spherical crown, that is, the central angle, is 30°. The height and radius of curvature of the spherical crown are uniquely determined by the bottom radius and the central angle. After implantation, the inner abutment segment is located in the inner cavity of the annulus fibrosus. After swelling, it abuts against the inner wall of the annulus fibrosus. Together with the outer sealing segment, it forms a bidirectional clamping effect on the inner and outer walls of the annulus fibrosus, providing an anti-dislodgement and limiting function. No additional fixation mechanism is required, and it does not cause any additional operation or damage to the vertebral bone.

[0059] Example 2:

[0060] This invention discloses a method for preparing a self-expanding occlusion implant for intervertebral disc annulus fibrosus defects, employing a polyethylene glycol / sodium alginate dual-network system, specifically including the following steps:

[0061] S1. Dissolve 10g of four-arm polyethylene glycol succinimide glutarate (4arm-PEG-SG), 0.5g of sodium alginate, and 20g of hydroxyapatite in 500mL of phosphate buffer (PBS) and stir at 4°C until completely clear to obtain component A; wherein the molecular weight of four-arm polyethylene glycol succinimide glutarate is 10 kDa. Then dissolve 3.6g of ε-polylysine hydrochloride in 500mL of borate buffer at pH 7.4 to obtain component B; wherein the molecular weight of ε-polylysine hydrochloride is 2 kDa.

[0062] S2. Mix components A and B in a volume ratio of 1:1 and immediately inject the mixture into a pre-shaped mold. Let it stand at room temperature to crosslink and obtain a wet gel, i.e., the first network.

[0063] S3. Remove the wet gel from the mold and immerse it in a 200 mmol / L CaCl2 solution at room temperature for 60 minutes to allow calcium ions to penetrate into the gel and undergo ionic cross-linking with the carboxyl groups on the sodium alginate chain to form a second network.

[0064] S4. Rinse the wet gel soaked in step S3 with PBS to remove residual calcium ions on the surface, then dry it in an oven at 37°C overnight to obtain a white porous solid dried body. Sterilize the dried body to obtain implant 1.

[0065] Example 3:

[0066] This invention discloses a method for preparing a self-expanding occlusion implant for intervertebral disc annulus fibrosus defects, employing a polyethylene glycol / sodium alginate dual-network system, specifically including the following steps:

[0067] S1. Dissolve 10g of four-arm polyethylene glycol succinimide glutarate (4arm-PEG-SG), 0.3g of sodium alginate, and 10g of hydroxyapatite in 500mL of phosphate buffer (PBS) and stir at 4°C until completely clear to obtain component A; wherein the molecular weight of four-arm polyethylene glycol succinimide glutarate is 10 kDa. Then dissolve 3.6g of ε-polylysine hydrochloride in 500mL of borate buffer at pH 7.4 to obtain component B; wherein the molecular weight of ε-polylysine hydrochloride is 2 kDa.

[0068] S2. Mix components A and B in a volume ratio of 1:1 and immediately inject the mixture into a pre-shaped mold. Let it stand at room temperature to crosslink and obtain a wet gel, i.e., the first network.

[0069] S3. Remove the wet gel from the mold and immerse it in a 200 mmol / L CaCl2 solution at room temperature for 60 minutes to allow calcium ions to penetrate into the gel and undergo ionic cross-linking with the carboxyl groups on the sodium alginate chain to form a second network.

[0070] S4. Rinse the wet gel soaked in step S3 with PBS to remove residual calcium ions on the surface, then dry it in an oven at 37°C overnight to obtain a white porous solid dried body. Sterilize the dried body to obtain implant 1.

[0071] Example 4:

[0072] A method for preparing a self-expanding occlusion implant for intervertebral disc annulus fibrosus defects, using a hyaluronic acid methacrylate / o-nitrobenzyl alcohol-modified polyethylene glycol photocrosslinking system, specifically includes the following steps:

[0073] Q1. Dissolve 6.7g of hyaluronic acid methacrylate (HAMA) powder in 100mL of pre-cooled phosphate buffer at 4℃ and pH 7.4, and place it in a 4℃ refrigerator overnight to allow it to completely dissolve, thus obtaining HAMA stock solution; wherein, the molecular weight of hyaluronic acid methacrylate is 40kDa and the grafting degree of hyaluronic acid methacrylate is 95%; Dissolve 200g of multi-arm o-nitrobenzyl alcohol-modified polyethylene glycol (PEG-NB) powder in 1L of pre-cooled phosphate buffer at 4℃ and pH 7.4, and shake to mix well under light-protected conditions, thus obtaining PEG-NB stock solution;

[0074] Q2. Mix 100 mL of HAMA stock solution and 300 mL of PEG-NB stock solution, add 3.2 g of photoinitiator LAP, and obtain a mixed solution;

[0075] Q3. Inject the mixed solution into a pre-shaped mold and cure it with ultraviolet light. Ultraviolet curing is performed by irradiating both sides of the mold with ultraviolet light at a wavelength of 365 nm for 300 seconds each, with an intensity of 300 milliwatts per square centimeter. This causes the methacrylate groups in hyaluronic acid methacrylate (HAMA) to undergo free radical polymerization, while multi-arm o-nitrobenzyl glycol (PEG-NB) participates in cross-linking through mercapto-olefin click chemistry to form a hydrogel. The hydrogel is then dried in an oven at 37°C overnight. After the process, it is sterilized to obtain implant 2.

[0076] Example 5:

[0077] A method for preparing a self-expanding occlusion implant for intervertebral disc annulus fibrosus defects, using a hyaluronic acid methacrylate / o-nitrobenzyl alcohol-modified polyethylene glycol photocrosslinking system, specifically includes the following steps:

[0078] Q1. Dissolve 10g of hyaluronic acid methacrylate (HAMA) powder in 100mL of pre-cooled phosphate buffer at 2℃ and pH 7.4, and place it in a refrigerator at 2℃ overnight to allow it to completely dissolve, thus obtaining HAMA stock solution; wherein, the molecular weight of hyaluronic acid methacrylate is 40kDa and the grafting degree of hyaluronic acid methacrylate is 85%; Dissolve 200g of multi-arm o-nitrobenzyl alcohol-modified polyethylene glycol (PEG-NB) powder in 1L of pre-cooled phosphate buffer at 2℃ and pH 7.4, and shake to mix well under light-protected conditions, thus obtaining PEG-NB stock solution;

[0079] Q2. Mix 100 mL of HAMA stock solution and 200 mL of PEG-NB stock solution, add 2.4 g of photoinitiator LAP, and obtain a mixed solution;

[0080] Q3. Inject the mixed solution into a pre-shaped mold and cure it with ultraviolet light. Ultraviolet curing is performed by irradiating both sides of the mold with ultraviolet light at a wavelength of 365 nm for 300 seconds each, with an intensity of 280 milliwatts per square centimeter. This causes the methacrylate groups in hyaluronic acid methacrylate (HAMA) to undergo free radical polymerization, while multi-arm o-nitrobenzyl glycol (PEG-NB) participates in cross-linking through mercapto-olefin click chemistry to form a hydrogel. The hydrogel is then dried in an oven at 37°C overnight. After the process, it is sterilized to obtain implant 2.

[0081] Example 6:

[0082] A method for preparing a self-expanding occlusion implant for intervertebral disc annulus fibrosus defects, using a hyaluronic acid methacrylate / o-nitrobenzyl alcohol-modified polyethylene glycol photocrosslinking system, specifically includes the following steps:

[0083] Q1. Dissolve 10g of hyaluronic acid methacrylate (HAMA) powder in 100mL of pre-cooled phosphate buffer at 4℃ and pH 7.4, and place it in a 4℃ refrigerator overnight to allow it to completely dissolve, thus obtaining HAMA stock solution; wherein, the molecular weight of hyaluronic acid methacrylate is 40kDa and the grafting degree of hyaluronic acid methacrylate is 90%; dissolve 200g of multi-arm o-nitrobenzyl alcohol-modified polyethylene glycol (PEG-NB) powder in 1L of pre-cooled phosphate buffer at 4℃ and pH 7.4, and shake to mix well under light-protected conditions, thus obtaining PEG-NB stock solution;

[0084] Q2. Mix 100 mL of HAMA stock solution and 250 mL of PEG-NB stock solution, add 2.8 g of photoinitiator LAP, and obtain a mixed solution;

[0085] Q3. Inject the mixed solution into a pre-shaped mold and cure it with ultraviolet light. Ultraviolet curing is performed by irradiating both sides of the mold with ultraviolet light at a wavelength of 365 nm for 300 seconds each, with an intensity of 320 milliwatts per square centimeter. This causes the methacrylate groups in hyaluronic acid methacrylate (HAMA) to undergo free radical polymerization, while multi-arm o-nitrobenzyl glycol (PEG-NB) participates in cross-linking through mercapto-olefin click chemistry to form a hydrogel. The hydrogel is then dried in an oven at 37°C overnight. After the process, it is sterilized to obtain implant 2.

[0086] Comparative Example 1:

[0087] Compared with Example 3, Comparative Example 1 did not add hydroxyapatite during the preparation of the self-expanding occlusion implant for intervertebral disc annulus fibrosus defects, while all other conditions remained unchanged.

[0088] Comparative Example 2:

[0089] Compared with Example 3, the amount of hydroxyapatite added in Comparative Example 2 was reduced to 5 wt% during the preparation of the self-expanding occlusion implant for intervertebral disc annulus fibrosus defects, while other conditions remained unchanged.

[0090] Comparative Example 3:

[0091] Compared with Example 3, Comparative Example 3 changed the drying method from air drying to freeze drying in the preparation process of the self-expanding occlusion implant for intervertebral disc annulus fibrosus defects, while keeping all other conditions unchanged.

[0092] Comparative Example 4:

[0093] Compared with Example 4, Comparative Example 4 changed the drying method from air drying to freeze drying in the preparation process of the self-expanding occlusion implant for intervertebral disc annulus fibrosus defects, while keeping all other conditions unchanged.

[0094] Comparative Example 5:

[0095] Compared with Example 4, Comparative Example 5 had an addition amount of 0.8 wt% of photoinitiator LAP in the preparation of a self-expanding occlusion implant for intervertebral disc annulus fibrosus defects, a volume ratio of HAMA mother liquor to PEG-NB mother liquor in the mixed solution of 1:5, and other conditions remained unchanged.

[0096] Experimental example:

[0097] The performance of the self-expanding occlusion implants prepared in Examples 2-6 and Comparative Examples 1-7 was determined:

[0098] I. Performance testing of implants using a polyethylene glycol / sodium alginate dual-network system:

[0099] First, the swelling properties were determined according to ASTM F2064-99 in phosphate-buffered saline (PBS) at 37±1°C with pH 7.4. Samples were removed periodically, and the surface liquid was gently absorbed with filter paper before weighing. The compressive strength and modulus were determined according to a modified method of ASTM D695: the swollen equilibrium sample was placed in a PBS immersion environment and compressed to 20% strain at a rate of 1 mm / min. The stress-strain curve was recorded, and the compressive modulus was calculated from the slope of the 10-30% strain range.

[0100] The results of the swelling test and mechanical test are shown in Table 1:

[0101] Table 1 Results of swelling and mechanical tests of M1

[0102]

[0103] According to the measurement results in Table 1, it can be seen that when the HAP addition amount increased from 0% (Comparative Example 1) to 20% (Example 2), the compressive strength of the material significantly increased from 0.67 MPa to 4.24 MPa, an increase of more than 6 times, fully demonstrating that hydroxyapatite (HAP) is a key component for achieving mechanical enhancement of the implant. Meanwhile, the drying process has a decisive impact on the material properties: although freeze-drying can improve the compressive strength to some extent (e.g., up to 2.60 MPa in Comparative Example 3), it leads to a significant decrease in the swelling rate and cannot complete effective expansion within the acceptable time window during surgery; in contrast, the 37°C low-temperature air-drying process retains the porous structure while taking into account both rapid water absorption and mechanical integrity, making it the preferred preparation method of this invention.

[0104] II. Performance testing of implants using the hyaluronic acid methacrylate / o-nitrobenzyl alcohol-based polyethylene glycol photocrosslinking system: The results of swelling and mechanical tests are shown in Table 2.

[0105] Table 2 Results of swelling and mechanical tests of M2

[0106]

[0107] According to the measurement results in Table 2, it can be seen that Example 4 (HAMA 6.7%, PEGoNB 20%, LAP 0.8%, ratio 1:3, pre-dried) achieved a swelling rate of 178% within 10 minutes and an equilibrium swelling rate of 189% within 15 minutes. At the same time, the compressive strength was 2.98 MPa and the compressive modulus was 4.44 MPa, thus satisfying the requirements of "rapid swelling" and "high mechanical properties". Therefore, Example 4 represents the core technical solution of this invention and is suitable for most clinical repair scenarios of intervertebral disc annulus fibrosus tears.

[0108] Comparative analysis of drying methods revealed that Comparative Example 4 (freeze-dried instead of Example 4), while maintaining the same formulation, showed a swelling rate of 155% after 10 minutes. Although the compressive strength slightly increased to 2.77 MPa, the swelling kinetics were significantly limited, indicating that while freeze-drying enhances structural density, it reduces the hydrogel's rapid water absorption capacity. Comparative Example 5, deviating from the optimal formulation and falling far below the clinically required threshold, represents the weakest control group.

[0109] III. Fatigue Testing

[0110] Fatigue testing of the implant was conducted under the following conditions: 1 Hz, ±1.17°, 10,000 cycles of torsion; the instrument used was a FT5000D tension-torsion combined fatigue tester. The results are shown in Table 3.

[0111] Table 3 Results of fatigue tests

[0112]

[0113] Based on the test results in Table 3, the present invention conducted a fatigue durability test of key embodiments 4 and 3 for 10,000 cycles, simulating the dynamic load environment (1 Hz, ±1.17° torsion) of the intervertebral disc during daily physiological activities. The test results showed that the initial compressive strength of embodiment 4 was 3.11 MPa and the compressive modulus was 4.64 MPa; after 10,000 fatigue cycles, its compressive strength increased to 3.24 MPa, and the modulus slightly decreased to 4.41 MPa. The sample showed no cracks, deformation, or structural damage, indicating that the implant not only maintained structural integrity under long-term dynamic stress, but also tended to stabilize or even slightly enhance its mechanical properties.

[0114] Meanwhile, the initial compressive strength of Example 3 (M1 system) was 1.61 MPa and the modulus was 1.43 MPa. The initial values ​​of the fatigue test were different from the results of the above mechanical test, which was due to different test batches. After fatigue, the strength dropped to 1.52 MPa and the modulus dropped to 1.29 MPa, with reductions of 5.6% and 9.1% respectively. However, these values ​​were still within the range of the original tissue mechanics, and the sample surface showed no damage or deformation, proving that it has sufficient anti-fatigue ability to cope with the daily movement load of the spine.

[0115] The above description is only a preferred embodiment of the present invention, but the scope of protection of the present invention is not limited thereto. Any equivalent substitutions or modifications made by those skilled in the art within the scope of the technology disclosed in the present invention, based on the technical solution and inventive concept of the present invention, should be covered within the scope of protection of the present invention.

[0116] The preferred embodiments of the present invention disclosed above are merely illustrative of the invention. These preferred embodiments do not exhaustively describe all details, nor do they limit the invention to specific implementations. Clearly, many modifications and variations can be made based on the content of this specification. This specification selects and specifically describes these embodiments to better explain the principles and practical applications of the invention, thereby enabling those skilled in the art to better understand and utilize the invention. The invention is limited only by the claims and their full scope and equivalents.

Claims

1. A self-expanding occlusion implant for intervertebral disc annulus fibrosus defects, characterized in that, The implant, in its dry state, is a solid porous body with a pre-formed three-dimensional shape, exhibiting an axially symmetrical dumbbell-shaped structure. Along its axial direction, it sequentially comprises an outer sealing section, a middle connecting section, and an inner abutting section. The middle connecting section is cylindrical. The outer sealing section and the inner abutting section abut against the outer and inner walls of the annulus fibrosus, respectively, forming a bidirectional clamping and anti-dislodgement limiting mechanism. The inner abutting section consists of coaxial parts a and b: part a is a disc-shaped base; part b is a spherical cap, with the circumference of the bottom surface of part b coinciding with the circumference of the inner end face of part a, and the central angle corresponding to the spherical cap being 20-40°. The implant has an open, interconnected pore structure and is composed of a multi-network polymer material consisting of at least two cross-linked networks, including a first network and a second network.

2. The self-expanding occlusion implant for intervertebral disc annulus fibrosus defects according to claim 1, characterized in that, The middle connecting body is disc-shaped with a diameter D of 4 to 6 mm and an axial length L of 8 to 12 mm; the outer sealing section is disc-shaped with a diameter of D+1 mm and an axial thickness of 1 mm; the a part has a diameter of D+2 mm and an axial thickness of 2 mm.

3. The self-expanding occlusion implant for intervertebral disc annulus fibrosus defects according to claim 1, characterized in that, The open connecting hole structure has a pore diameter ranging from 10 to 500 micrometers.

4. A self-expanding occlusion implant for intervertebral disc annulus fibrosus defects according to any one of claims 1-3, characterized in that, The multi-network polymer material is any of the following systems: M1, polyethylene glycol / sodium alginate dual network system; M2, a photocrosslinking system of hyaluronic acid methacrylate / o-nitrobenzyl alcohol-modified polyethylene glycol.

5. A method for preparing a self-expanding occlusion implant for intervertebral disc annulus fibrosus defects according to any one of claims 1-4, characterized in that, The M1 includes the following steps: S1. Dissolve four-armed polyethylene glycol succinimide glutarate, sodium alginate, and hydroxyapatite together in phosphate buffer and stir until clear to obtain component A; dissolve the amine crosslinking agent in borate buffer to obtain component B; S2. Mix components A and B in a volume ratio of 1:1 and inject the mixture into a dumbbell-shaped mold. Let it stand at room temperature for in vitro cross-linking and curing to form a wet gel, i.e., the first network. S3. Remove the wet gel from the mold and immerse it in CaCl2 solution at room temperature to allow calcium ions to penetrate into the gel and crosslink with the carboxyl groups on the sodium alginate chain to form a second network. S4. Rinse the wet gel soaked in step S3 with phosphate buffer to remove residual calcium ions from the surface, dry it to obtain a white porous solid dry body, sterilize it, and obtain implant 1.

6. The method for preparing a self-expanding occlusion implant for intervertebral disc annulus fibrosus defects according to claim 5, characterized in that, In S1, the amine crosslinking agent is one or both of ε-polylysine hydrochloride and trilysine.

7. The method for preparing a self-expanding occlusion implant for intervertebral disc annulus fibrosus defects according to claim 5, characterized in that, In S1, the ratio of the four-arm polyethylene glycol succinimide glutarate, sodium alginate, hydroxyapatite, and phosphate buffer is 100 mg: (3-5) mg: (100-200) mg: 5 mL; the ratio of the amine crosslinking agent to borate buffer is 36 mg: 5 mL.

8. A method for preparing a self-expanding occlusion implant for intervertebral disc annulus fibrosus defects according to any one of claims 1-4, characterized in that, The M2 includes the following steps: Q1. Dissolve hyaluronic acid methacrylate powder in pre-cooled phosphate buffer at 0-4℃ to obtain HAMA stock solution; dissolve multi-arm o-nitrobenzyl alcohol-modified polyethylene glycol powder in pre-cooled phosphate buffer and mix by shaking under light-protected conditions to obtain PEG-NB stock solution. Q2. Mix the HAMA mother liquor and PEG-NB mother liquor, add the photoinitiator, and obtain a mixed solution; Q3. Inject the mixed solution into the mold and cure it under ultraviolet light to form a hydrogel; dry and sterilize the hydrogel in sequence to obtain implant 2.

9. A method for preparing a self-expanding occlusion implant for intervertebral disc annulus fibrosus defects according to claim 8, characterized in that, The concentrations of HAMA mother liquor, PEG-NB mother liquor and photoinitiator mother liquor in the mixed solution in Q2 are (6.7wt%-9wt%), (20wt%-45wt%) and (0.5wt%-1wt%), respectively.

10. A method for preparing a self-expanding occlusion implant for intervertebral disc annulus fibrosus defects according to claim 8, characterized in that, The volume ratio of HAMA mother liquor to PEG-NB mother liquor in the mixed solution of Q2 is (1-2):(3-5).

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