Self-healing bionic intervertebral disc capable of improving service stability and nucleus pulposus preparation method thereof

Abstract

The invention relates to a self-healing bionic intervertebral disc capable of improving service stability and a nucleus pulposus preparation method of the self-healing bionic intervertebral disc, and belongs to the field of bionic implant prostheses. The self-healing bionic intervertebral disc capable of improving the service stability is composed of an upper end plate, a bionic fibrous ring layer, a lower end plate and a bionic nucleus pulposus, the bionic nucleus pulposus adopts dynamic cross-linked hydrogel to simulate the viscoelasticity and moisture regulation function of a natural nucleus pulposus, and the buffering and self-healing characteristics of the bionic intervertebral disc are achieved; the bionic fiber ring layer achieves gradient mechanical properties through directionally-arranged composite materials, and three-dimensional physiological movement of the artificial intervertebral disc close to the lumbar vertebra of a human body is achieved. The bionic intervertebral disc provided by the invention is matched with viscoelasticity of a natural intervertebral disc, recovers natural matching with three-dimensional physiological movement of a human spine, can buffer dynamic load and maintain intervertebral height, can perform micro-injury self-repair through dynamic crosslinking of chemical bonds in bionic nucleus pulposus, and has a good application prospect. And the kinematic mechanical stability of long-term service in a human body is realized.

Description

Technical Field

[0001] The present invention relates to the field of bionic implant prostheses, and in particular to a self-healing bionic intervertebral disc capable of improving service stability and a method for preparing a nucleus pulposus thereof. Background Art

[0002] The human lumbar intervertebral disc is a cartilaginous tissue located between adjacent vertebrae, mainly composed of the nucleus pulposus, annulus fibrosus and endplates, which is responsible for supporting the spine and providing flexibility. With age, the human lumbar intervertebral disc will inevitably degenerate, with clinical manifestations such as nucleus pulposus dehydration and annulus fibrosus rupture, which in turn causes lower back pain and leads to abnormal movement of spinal segments and biomechanical instability. Lumbar disc degeneration can cause low back pain in patients, and in severe cases, it can cause lower limb movement disorders or disability, causing great pain and heavy economic burden to patients. Especially with the intensification of global aging, lumbar disc degeneration has become one of the world's major musculoskeletal diseases.

[0003] At present, one of the effective surgical methods for the clinical treatment of moderate and severe degenerative discs is to use artificial discs to replace degenerative discs. Literature research shows that artificial discs currently used or studied in clinical practice can be roughly divided into metal-metal type, ceramic-ceramic type, metal-polymer type and polymer-polymer type according to their material composition. Since these materials that constitute artificial discs are essentially continuous solid hard materials or harder materials, and most of them are homogeneous and isotropic stiffness designs, the current artificial discs cannot have both good buffering function and matching the three-dimensional physiological movement of the spine after implantation. In addition, most of these materials lack self-repairing ability. In clinical use, the accumulation of micro-damage can easily cause the artificial disc to fail in the patient's body and require secondary surgery, which in turn causes great pain to the patient.

[0004] Current artificial intervertebral disc prostheses have not yet achieved the ability to maintain intervertebral height while also having good cushioning functions, matching the three-dimensional physiological movement of the spine, and autonomously repairing micro-damages. This has seriously affected the kinematic mechanical stability of artificial intervertebral discs in long-term service in the human body and needs to be urgently addressed.

[0005] Biomechanical studies have shown that the intervertebral disc achieves its various biomechanical functions through the synergistic action of the nucleus pulposus and the annulus fibrosus: the nucleus pulposus, as a hydrophilic gel matrix, has excellent viscoelasticity and swelling properties. It generates internal pressure through water absorption and swelling, thereby forming a hydrostatic pressure system to cope with axial loads, which can effectively buffer the axial dynamic loads of the spine and maintain the intervertebral height effectively; the annulus fibrosus is composed of concentrically arranged parallel collagen fibers, and the collagen fibers in adjacent layers are cross-arranged. Each layer of collagen fibers has a certain inclination angle with the end plate, and this inclination angle gradually increases from the outside to the inside, supporting the realization of its anisotropic mechanical properties. This "liquid-solid" coupling mechanism enables the intervertebral disc to disperse stress through the deformation of the nucleus pulposus during compression, while the elastic retraction of the annulus fibrosus maintains structural stability. During spinal movement, the mechanical property differences in different regions of the annulus fibrosus and the deformation of the nucleus pulposus together achieve the three-dimensional natural physiological movement of the lumbar segment. Summary of the Invention

[0006] The present invention designs a self-healing bionic intervertebral disc that can improve service stability by preparing a bionic nucleus pulposus with excellent viscoelasticity, swelling properties and self-healing properties, combined with the design of a bionic annulus fibrosus layer with gradient mechanical properties through fiber interweaving and annular layer structure, which can effectively buffer dynamic loads, maintain intervertebral height, and restore the normal three-dimensional physiological movement of the spine; in addition, the bionic nucleus pulposus prepared by the preparation method of its nucleus pulposus can also autonomously repair the micro-damage of the bionic intervertebral disc through the dynamic cross-linking of chemical bonds, significantly improving the kinematic and mechanical stability of the bionic intervertebral disc during long-term service in the body.

[0007] The self-healing bionic intervertebral disc that can improve service stability includes an upper end plate, a bionic annulus fibrosus layer, a lower end plate and a bionic nucleus pulposus. Among them, the bionic annulus fibrosus layer is sleeved outside the bionic nucleus pulposus, and the bionic annulus fibrosus layer and the bionic nucleus pulposus are clamped between the upper end plate and the lower end plate. Fixed teeth are respectively arranged on the outer sides of the upper end plate and the lower end plate.

[0008] The bionic annulus fibrosus layer described above includes a first annulus fibrosus layer, a second annulus fibrosus layer, a third annulus fibrosus layer and a fourth annulus fibrosus layer, and the first annulus fibrosus layer, the second annulus fibrosus layer, the third annulus fibrosus layer and the fourth annulus fibrosus layer are fixedly arranged in sequence from the outside to the inside; The first annulus fibrosus layer includes a first annulus fibrosus matrix layer and a first group of collagen fibers. The first group of collagen fibers is composed of a number of front-end first collagen fibers and a number of rear-end first collagen fibers; both the front-end first collagen fibers and the rear-end first collagen fibers are arranged on the outside of the first annulus fibrosus matrix layer. A number of front-end first collagen fibers are arranged obliquely and parallelly, and a number of rear-end first collagen fibers are arranged obliquely and parallelly. After the first annulus fibrosus matrix layer is unfolded, a number of front-end first collagen fibers and a number of rear-end first collagen fibers are all arranged parallelly on the same plane; The second annulus fibrosus layer includes a second annulus fibrosus matrix layer and a second collagen fiber group, and the second collagen fiber group is composed of a front-end second collagen fiber and a rear-end second collagen fiber; both the front-end second collagen fiber and the rear-end second collagen fiber are arranged outside the second annulus fibrosus matrix layer, a plurality of front-end second collagen fibers are arranged obliquely and parallelly, a plurality of rear-end second collagen fibers are arranged obliquely and parallelly, and after the second annulus fibrosus matrix layer is unfolded, a plurality of front-end second collagen fibers and a plurality of rear-end second collagen fibers are arranged parallelly in the same plane, and the inclination directions of the front-end second collagen fiber and the rear-end second collagen fiber are opposite to the inclination directions of the front-end first collagen fiber and the rear-end first collagen fiber; The third annulus fibrosus layer includes a third annulus fibrosus matrix layer and a third collagen fiber group, and the third collagen fiber group is composed of a front-end third collagen fiber and a rear-end third collagen fiber; both the front-end third collagen fiber and the rear-end third collagen fiber are arranged outside the third annulus fibrosus matrix layer, a plurality of front-end third collagen fibers are arranged obliquely and parallelly, a plurality of rear-end third collagen fibers are arranged obliquely and parallelly, and after the third annulus fibrosus matrix layer is unfolded, a plurality of front-end third collagen fibers and a plurality of rear-end third collagen fibers are arranged parallelly in the same plane, and the inclination directions of the front-end third collagen fiber and the rear-end third collagen fiber are the same as the inclination directions of the front-end first collagen fiber and the rear-end first collagen fiber; The fourth annulus fibrosus layer includes a fourth annulus fibrosus matrix layer and a fourth collagen fiber group, and the fourth collagen fiber group is composed of a front-end fourth collagen fiber and a rear-end fourth collagen fiber; both the front-end fourth collagen fiber and the rear-end fourth collagen fiber are arranged outside the fourth annulus fibrosus matrix layer, a plurality of front-end fourth collagen fibers are arranged obliquely and parallelly, a plurality of rear-end fourth collagen fibers are arranged obliquely and parallelly, and after the fourth annulus fibrosus matrix layer is unfolded, a plurality of front-end fourth collagen fibers and a plurality of rear-end fourth collagen fibers are arranged parallelly in the same plane, and the inclination directions of the front-end fourth collagen fiber and the rear-end fourth collagen fiber are the same as the inclination directions of the front-end second collagen fiber and the rear-end second collagen fiber.

[0009] The described bionic annulus fibrosus layer is 3D printed integrally, and the first annulus fibrosus matrix layer, the second annulus fibrosus matrix layer, the third annulus fibrosus matrix layer and the fourth annulus fibrosus matrix layer are 3D printed with polyurethane polymer materials with gradually decreasing hardness, and the first collagen fiber group, the second collagen fiber group, the third collagen fiber group and the fourth collagen fiber group are 3D printed with polyurethane resin.

[0010] The included angles formed by the first collagen fiber group, the second collagen fiber group, the third collagen fiber group and the fourth collagen fiber group with the upper endplate surface increase in a gradient from the outside to the inside, and the gradient of the included angle is 5 degrees.

[0011] The included angle formed by the first group of collagen fibers and the upper endplate surface is 30 degrees, the included angle formed by the second group of collagen fibers and the upper endplate surface is 35 degrees, the included angle formed by the third group of collagen fibers and the upper endplate surface is 40 degrees, and the included angle formed by the fourth group of collagen fibers and the upper endplate surface is 45 degrees.

[0012] The cross-sections of the upper endplate, the bionic fiber annulus layer, the lower endplate, and the bionic nucleus pulposus are "D"-shaped; the materials of the upper endplate and the lower endplate are polyetheretherketone, and the outer surfaces of the upper endplate and the lower endplate are plated with a hydroxyapatite layer.

[0013] A preparation method of a self-healing bionic intervertebral disc nucleus pulposus that can improve service stability includes the following steps: Step 1: Under room temperature conditions, modify hyaluronic acid with sodium periodate to prepare sodium periodate-modified hyaluronic acid: Dissolve 2 g of sodium hyaluronate in 200 mL of distilled water, stir under the condition of 200 revolutions per minute of a magnetic stirrer to fully dissolve sodium hyaluronate, and obtain solution A; Then add sodium periodate to solution A so that the molar ratio of sodium periodate to sodium hyaluronate is 1:1, and stir for 24 hours under dark conditions to obtain solution B; Add 2 mL of ethylene glycol to solution B, react for 1 - 2 h to remove unreacted sodium periodate, and obtain solution C; Put the obtained solution C into a dialysis bag with a molecular weight cut-off of 10,000 - 16,000 and dialyze for 3 - 7 days, and then freeze-dry the dialyzed solution C to obtain sodium periodate-modified hyaluronic acid, that is, OHA. Among them, the molar ratio of hyaluronic acid to sodium periodate is 1:1, and the molecular weight of hyaluronic acid is 150,000 - 250,000; Step 2: Prepare a hydrogel polymer: Heat gelatin to 37 °C to successfully dissolve it into a gelatin solution; Take the OHA obtained in Step 1 and the above-mentioned gelatin solution and dissolve them simultaneously in a 0.1 mol / L borax aqueous solution so that the mass concentration of OHA in the unit volume solution is 10% and the mass concentration of gelatin is 4%; Ultrasonically stir the above mixture for 2 minutes and then magnetically stir for 30 minutes to obtain a hydrogel polymer; Step 3: Finally, inject the above hydrogel polymer into a nucleus pulposus mold, and let it stand and cure at room temperature for 16 - 28 hours. After the hydrogel in-situ polymerizes and forms, an artificial nucleus pulposus prosthesis is obtained.

[0014] In Step 1, the dialysis time of solution C in the dialysis bag is 5 days, and the molecular weight cut-off of the used dialysis bag is 14,000.

[0015] In the second step, the conditions for ultrasonic stirring are a power ratio of 100%, a closed temperature of 37 °C, and a probe of 3 mm. The conditions for magnetic stirring are a magnetic stirrer speed of 200 revolutions per minute.

[0016] In the third step, the curing time of the hydrogel polymer in the nucleus pulposus mold is 24 hours.

[0017] The working principle and process of the present invention: Inspired by the functional structure and material properties of the biological intervertebral disc, the self-healing bionic intervertebral disc capable of improving service stability includes an upper endplate and a lower endplate, a bionic nucleus pulposus, and a bionic annulus fibrosus layer. The upper end of the bionic annulus fibrosus layer is fixed to the lower surface of the upper endplate, and the lower end is fixed to the upper surface of the lower endplate. Fixed teeth are provided on the surfaces of the upper and lower endplates, and the fixed teeth play an initial fixing role after the bionic intervertebral disc is implanted.

[0018] The bionic nucleus pulposus prepared by the preparation method of the self-healing bionic intervertebral disc nucleus pulposus capable of improving service stability according to the present invention has excellent viscoelasticity, swelling property, and self-healing property. Periodate is used to modify HA (hyaluronic acid) to make it have highly reactive dialdehyde groups, and then complexation reactions are carried out with borax and gelatin respectively, and Schiff base reactions form dynamic imine bonds and reversible borate bonds. When subjected to external impact, the weaker reversible bonds inside it will absorb energy to protect the main covalent bonds. Once the external force is removed, these chemical bonds can self-repair, enabling the damaged bionic intervertebral disc to restore its shape and function. Excellent viscoelasticity enables it to respond quickly and release stress when deformed, dissipate energy in large physiological deformations at high load frequencies, and make its internal fluidity at low frequencies. In addition, the rapid swelling ability helps to maintain sufficient moisture in the material and restore the elasticity and buffering ability of the intervertebral disc.

[0019] The inclination directions of the first collagen fiber group, the second collagen fiber group, the third collagen fiber group, and the fourth collagen fiber group of the bionic annulus fibrosus layer are arranged in a cross pattern in sequence. When the spine is subjected to external loads, the bionic nucleus pulposus transfers the vertical pressure to the bionic annulus fibrosus layer through its own deformation and converts it into a radial force that expands around, and then the bionic annulus fibrosus layer gradually transfers the load to disperse the stress, thereby avoiding stress concentration. The cross arrangement between different layers of collagen fiber groups can prevent the bionic nucleus pulposus from bulging excessively in a certain direction under pressure, reduce the relative sliding between layers, and avoid delamination and rupture under the action of external forces.

[0020] The inclination angles formed by the first collagen fiber group, the second collagen fiber group, the third collagen fiber group, and the fourth collagen fiber group with the endplate surface increase in a gradient from the outside to the inside. Among them, the angle between the first collagen fiber group of the outermost first annulus fibrosus layer and the upper surfaces of the front parts of the upper and lower endplates is the smallest. The outer fibers of the bionic intervertebral disc are mainly used to resist the tensile forces generated by loads such as bending and torsion. For example, when the body twists, the outermost fibers of the bionic intervertebral disc, that is, the front-end first collagen fibers and the rear-end first collagen fibers, are stretched, which can effectively counteract this tensile force and avoid fiber tearing. The fiber orientation of the fourth collagen fiber group in the innermost fourth annulus fibrosus layer acts synergistically with the gel-like structure of the bionic nucleus pulposus, and can effectively bear the compressive load and maintain the height of the bionic intervertebral disc.

[0021] The hardness of the first annulus fibrosus matrix layer, the second annulus fibrosus matrix layer, the third annulus fibrosus matrix layer, and the fourth annulus fibrosus matrix layer decreases in turn. The outermost first annulus fibrosus matrix layer has the greatest hardness, which can limit the excessive movement of the intervertebral disc and prevent the intervertebral disc from prolapsing or tearing. The fourth annulus fibrosus matrix layer close to the bionic nucleus pulposus inside has the lowest hardness.

[0022] The materials of the upper endplate and the lower endplate are polyetheretherketone, and the outer surfaces of the upper endplate and the lower endplate are plated with a hydroxyapatite layer, which can promote biocompatibility after implantation.

[0023] Advantages of the present invention: (1) The present invention realizes the self-healing property of the bionic intervertebral disc through the dynamic cross-linking of the chemical bonds of the bionic nucleus pulposus. The HA modified by periodate undergoes complexation reactions with borax and gelatin respectively, and Schiff base reactions form dynamic imine bonds and reversible borate ester bonds. When micro-damage occurs due to external impact, these dynamic chemical bonds can self-repair, enabling the damaged bionic intervertebral disc to restore its shape and function, reducing the frequency of artificial maintenance or replacement of the bionic intervertebral disc, and extending its service life.

[0024] (2) The present invention constructs a buffer mechanism for the bionic intervertebral disc through the synergistic action of the bionic nucleus pulposus and the bionic annulus fibrosus layer. The bionic nucleus pulposus provides hydraulic buffering, while the bionic annulus fibrosus layer provides structural restraint. The load is transmitted to the bionic annulus fibrosus layer through the deformation of the bionic nucleus pulposus itself to disperse stress. At the same time, the bionic annulus fibrosus layer restricts the excessive expansion and deformation of the bionic nucleus pulposus through elastic restraint, enabling the bionic intervertebral disc to maintain its structural integrity and functionality after high-impact loads.

[0025] (3) By regulating the inclination angle of collagen fibers and the matrix layer hardness in different annulus fibrosus layers, the present invention realizes the mechanical properties of the bionic intervertebral disc in different regions, restores the anisotropic functional characteristics of the biological intervertebral disc, and further enables the bionic intervertebral disc to better match the three-dimensional physiological movement of the spine after implantation. At the same time, the gradient change of the inclination angle of collagen fibers from the outside to the inside enables the internal annulus fibrosus layers to effectively bear the compression load in cooperation with the bionic nucleus pulposus and maintain the height of the bionic intervertebral disc, while the external annulus fibrosus layer can prevent fiber tearing caused by tensile forces generated by loads such as torsion, thus achieving structural stability. Brief Description of the Drawings

[0026] Figure 1 It is a three-dimensional schematic diagram of the bionic intervertebral disc according to Embodiment 1 of the present invention.

[0027] Figure 2 It is an exploded view of the structure of the bionic intervertebral disc according to Embodiment 1 of the present invention.

[0028] Figure 3 It is a schematic diagram of the structure of the annulus fibrosus layer of the bionic intervertebral disc according to Embodiment 1 of the present invention.

[0029] Figure 4 It is a rear view of the bionic intervertebral disc according to Embodiment 1 of the present invention.

[0030] Figure 5 It is an unfolded schematic diagram of the first annulus fibrosus layer of the bionic intervertebral disc according to Embodiment 1 of the present invention.

[0031] Figure 6 It is an unfolded schematic diagram of the second annulus fibrosus layer of the bionic intervertebral disc according to Embodiment 1 of the present invention.

[0032] Figure 7 It is an unfolded schematic diagram of the third annulus fibrosus layer of the bionic intervertebral disc according to Embodiment 1 of the present invention.

[0033] Figure 8 It is an unfolded schematic diagram of the fourth annulus fibrosus layer of the bionic intervertebral disc according to Embodiment 1 of the present invention.

[0034] Figure 9 It is a schematic diagram of the preparation process of the bionic nucleus pulposus according to Embodiment 2 of the present invention.

[0035] Figure 10 It is a dynamic cyclic load experimental diagram and a front-back shape comparison diagram of the hydrogel polymer under 50% strain in the preparation of the bionic nucleus pulposus according to the embodiment of the present invention.

[0036] Figure 11 It is a dynamic frequency scanning curve diagram according to the embodiment of the present invention.

[0037] Figure 12 It is a picture of the swelling performance test of the hydrogel polymer according to the embodiment of the present invention.

[0038] Figure 13This is the swelling performance curve of the hydrogel polymer in the embodiment of the present invention.

[0039] Figure 14 This is the test picture of the self-healing performance of the hydrogel polymer in the embodiment of the present invention.

[0040] In the figure: 1. Upper endplate, 21. First annulus fibrosus layer, 211. First annulus fibrosus matrix layer, 2121. Front-end first collagen fiber, 2122. Rear-end first collagen fiber, 22. Second annulus fibrosus layer, 221. Second annulus fibrosus matrix layer, 2221. Front-end second collagen fiber, 2222. Rear-end second collagen fiber, 23. Third annulus fibrosus layer, 231. Third annulus fibrosus matrix layer, 2321. Front-end third collagen fiber, 2322. Rear-end third collagen fiber, 24. Fourth annulus fibrosus layer, 241. Fourth annulus fibrosus matrix layer, 2421. Front-end fourth collagen fiber, 2422. Rear-end fourth collagen fiber, 3. Lower endplate, 4. Bionic nucleus pulposus, 5. Fixing teeth. Detailed implementation manners

[0041] Please refer to Figures 1 to 8 shown in the figure, which is Embodiment 1 of the present invention.

[0042] The self-healing bionic intervertebral disc that can improve service stability includes an upper endplate 1, a bionic annulus fibrosus layer, a lower endplate 3 and a bionic nucleus pulposus 4, wherein the bionic annulus fibrosus layer is sleeved outside the bionic nucleus pulposus 4, and the bionic annulus fibrosus layer and the bionic nucleus pulposus 4 are clamped between the upper endplate 1 and the lower endplate 3, and fixing teeth 5 are respectively arranged on the outer sides of the upper endplate 1 and the lower endplate 3.

[0043] The bionic annulus fibrosus layer includes a first annulus fibrosus layer 21, a second annulus fibrosus layer 22, a third annulus fibrosus layer 23 and a fourth annulus fibrosus layer 24, and the first annulus fibrosus layer 21, the second annulus fibrosus layer 22, the third annulus fibrosus layer 23 and the fourth annulus fibrosus layer 24 are fixedly arranged in sequence from outside to inside; The first annulus fibrosus layer 21 includes a first annulus fibrosus matrix layer 211 and a first group of collagen fibers. The first group of collagen fibers is composed of a number of front-end first collagen fibers 2121 and a number of rear-end first collagen fibers 2122; both the front-end first collagen fibers 2121 and the rear-end first collagen fibers 2122 are arranged outside the first annulus fibrosus matrix layer 211. A number of front-end first collagen fibers 2121 are arranged obliquely and parallelly, and a number of rear-end first collagen fibers 2122 are arranged obliquely and parallelly. After the first annulus fibrosus matrix layer 211 is unfolded, a number of front-end first collagen fibers 2121 and a number of rear-end first collagen fibers 2122 are all arranged parallelly on the same plane; The second annulus fibrosus layer 22 includes a second annulus fibrosus matrix layer 221 and a second collagen fiber group, and the second collagen fiber group consists of a front-end second collagen fiber 2221 and a rear-end second collagen fiber 2222; both the front-end second collagen fiber 2221 and the rear-end second collagen fiber 2222 are disposed outside the second annulus fibrosus matrix layer 221, a plurality of front-end second collagen fibers 2221 are arranged obliquely and parallelly, a plurality of rear-end second collagen fibers 2222 are arranged obliquely and parallelly, and after the second annulus fibrosus matrix layer 221 is unfolded, a plurality of front-end second collagen fibers 2221 and a plurality of rear-end second collagen fibers 2222 are parallelly arranged in the same plane, and the inclination directions of the front-end second collagen fiber 2221 and the rear-end second collagen fiber 2222 are opposite to the inclination directions of the front-end first collagen fiber 2121 and the rear-end first collagen fiber 2122; The third annulus fibrosus layer 23 includes a third annulus fibrosus matrix layer 231 and a third collagen fiber group, and the third collagen fiber group consists of a front-end third collagen fiber 2321 and a rear-end third collagen fiber 2322; both the front-end third collagen fiber 2321 and the rear-end third collagen fiber 2322 are disposed outside the third annulus fibrosus matrix layer 231, a plurality of front-end third collagen fibers 2321 are arranged obliquely and parallelly, a plurality of rear-end third collagen fibers 2322 are arranged obliquely and parallelly, and after the third annulus fibrosus matrix layer 231 is unfolded, a plurality of front-end third collagen fibers 2321 and a plurality of rear-end third collagen fibers 2322 are parallelly arranged in the same plane, and the inclination directions of the front-end third collagen fiber 2321 and the rear-end third collagen fiber 2322 are the same as the inclination directions of the front-end first collagen fiber 2121 and the rear-end first collagen fiber 2122; The fourth annulus fibrosus layer 24 includes a fourth annulus fibrosus matrix layer 241 and a fourth collagen fiber group, and the fourth collagen fiber group consists of a front-end fourth collagen fiber 2421 and a rear-end fourth collagen fiber 2422; both the front-end fourth collagen fiber 2421 and the rear-end fourth collagen fiber 2422 are disposed outside the fourth annulus fibrosus matrix layer 241, a plurality of front-end fourth collagen fibers 2421 are arranged obliquely and parallelly, a plurality of rear-end fourth collagen fibers 2422 are arranged obliquely and parallelly, and after the fourth annulus fibrosus matrix layer 241 is unfolded, a plurality of front-end fourth collagen fibers 2421 and a plurality of rear-end fourth collagen fibers 2422 are parallelly arranged in the same plane, and the inclination directions of the front-end fourth collagen fiber 2421 and the rear-end fourth collagen fiber 2422 are the same as the inclination directions of the front-end second collagen fiber 2221 and the rear-end second collagen fiber 2222.

[0044] The described bionic annulus fibrosus layer is 3D printed integrally, and the first annulus fibrosus matrix layer 211, the second annulus fibrosus matrix layer 221, the third annulus fibrosus matrix layer 231, and the fourth annulus fibrosus matrix layer 241 are 3D printed with polyurethane resins having gradually decreasing hardness, and the first collagen fiber group, the second collagen fiber group, the third collagen fiber group, and the fourth collagen fiber group are 3D printed with polyurethane resins.

[0045] The included angles formed by the first collagen fiber group, the second collagen fiber group, the third collagen fiber group, and the fourth collagen fiber group with the surface of the upper endplate 1 increase in a gradient from outside to inside, and the gradient of the included angle is 5 degrees.

[0046] The included angle formed by the first collagen fiber group with the surface of the upper endplate 1 is 30 degrees, the included angle formed by the second collagen fiber group with the surface of the upper endplate 1 is 35 degrees, the included angle formed by the third collagen fiber group with the surface of the upper endplate 1 is 40 degrees, and the included angle formed by the fourth collagen fiber group with the surface of the upper endplate 1 is 45 degrees.

[0047] The cross-sections of the upper endplate 1, the bionic annulus fibrosus layer, the lower endplate 3, and the bionic nucleus pulposus 4 are "D"-shaped; the upper endplate 1 and the lower endplate 3 are made of polyetheretherketone (peek), and the outer surfaces of the upper endplate 1 and the lower endplate 3 are coated with a hydroxyapatite layer.

[0048] Please refer to Figure 9 , which is Example 2 of the present invention.

[0049] A preparation method of a self-healing bionic intervertebral disc nucleus pulposus capable of improving service stability includes the following steps: Step 1: Under room temperature conditions, modify hyaluronic acid with sodium periodate to prepare sodium periodate-modified hyaluronic acid: Dissolve 2 g of sodium hyaluronate in 200 mL of distilled water, stir under the condition of 200 revolutions per minute of a magnetic stirrer to fully dissolve sodium hyaluronate to obtain solution A; Then add sodium periodate to solution A so that the molar ratio of sodium periodate to sodium hyaluronate is 1:1, and stir for 24 hours under dark conditions to obtain solution B; Add 2 mL of ethylene glycol to solution B, react for 1-2 h to remove unreacted sodium periodate to obtain solution C; Put the obtained solution C into a dialysis bag with a molecular weight cut-off of 10,000-16,000 and dialyze for 3-7 days, and then freeze-dry the dialyzed solution C to obtain sodium periodate-modified hyaluronic acid, that is, OHA. Among them, the molar ratio of hyaluronic acid to sodium periodate is 1:1, the molecular weight of hyaluronic acid is 150,000-250,000; the dialysis time of solution C in the dialysis bag is 5 days, and the molecular weight cut-off of the used dialysis bag is 14,000; Step 2: Prepare a hydrogel polymer: The gelatin was heated to 37 °C and successfully dissolved into a gelatin solution; Take the OHA obtained in Step 1 and the above-mentioned gelatin solution and dissolve them simultaneously in a 0.1 mol / L borax aqueous solution, so that the mass concentration of OHA in the unit volume solution is 10%, and the mass concentration of gelatin is 4%; The above mixture was ultrasonically stirred for 2 minutes and then magnetically stirred for 30 minutes to obtain a hydrogel polymer; the conditions for ultrasonic stirring were a power ratio of 100%, a closed temperature of 37 °C, and a probe of 3 mm, and the conditions for magnetic stirring were a magnetic stirrer at 200 revolutions per minute; Step 3: Finally, inject the above hydrogel polymer into a nucleus pulposus mold and let it stand and cure at room temperature for 16 - 28 hours. After the hydrogel in-situ polymerizes and forms, an artificial nucleus pulposus prosthesis is obtained; the curing time of the hydrogel polymer in the nucleus pulposus mold is 24 hours.

[0050] Please refer to Figure 10 This is Example 3 of the present invention, the bionic nucleus pulposus dynamic compression test.

[0051] 1. Experimental method: This test uses a universal mechanical testing machine to perform a compression test on a bionic nucleus pulposus with a diameter of 25 mm and a height of 10 mm at a speed of 10 mm / min. The bionic nucleus pulposus is compressed to a constant compressive strain of 50%, and then the load is unloaded to 0. This process is repeated cyclically 5 times to evaluate the mechanical properties of the bionic nucleus pulposus under dynamic compressive loads.

[0052] 2. Experimental results: As Figure 10 shown, significant energy dissipation was observed during the continuous cyclic compression process of up to 5 times for the bionic nucleus pulposus in this example, indicating an energy absorption ability. The subsequent 4 stress-strain curves almost remained overlapping. Although the dissipated energy decreased significantly after the first cycle and showed the minimum energy dissipation, the hysteresis behavior of cyclic loading was still relatively obvious. Importantly, we found that the deformation observed after the cyclic compression test of the bionic nucleus pulposus was very small and could fully recover from the large deformation after compression, which proved the self-recovery characteristic of the bionic nucleus pulposus in this example after deformation.

[0053] Please refer to Figure 11 This is Example 4 of the present invention, the bionic nucleus pulposus dynamic mechanical analysis (DMA).

[0054] 1. Experimental method: Use TA (TA Instruments ElectroForce 3300 Series, Water Technology Co., Ltd., USA, equipment name) to study and detect the rheological properties and parameters of the nucleus pulposus prosthesis. The diameter of the sample mold for shaping and curing is 25 mm, and the height is 10 mm. The frequency sweep test is carried out at room temperature, the strain is set to 10%, and the frequency is gradually increased from 0.1 Hz to 10 Hz from low to high. Three important parameters are obtained from this test: storage modulus (G'), loss modulus (G"), and phase angle δ (tan δ = G" / G').

[0055] 2. Experimental results: The phase angle measures the internal dissipation of the nucleus pulposus prosthesis. For an ideal elastic material (solid), the phase shift angle value is equal to 0°, while for an ideal fluid, the phase shift angle value is 90°, and it cannot store energy.

[0056] The nucleus pulposus shows significant viscoelastic solid and viscoelastic fluid behaviors in dynamic mechanical analysis. The results of the dynamic frequency sweep show that the overall trend of the phase angle of the artificial nucleus pulposus of the present invention increases with the increase of frequency, indicating that the artificial nucleus pulposus becomes harder with the increase of frequency, but the phase angle δ value is always less than 45°, which reflects the more "solid-like" behavior of the artificial nucleus pulposus under dynamic conditions and conforms to the viscoelastic characteristics of the human nucleus pulposus.

[0057] Please refer to Figure 12 and Figure 13 for Example 5 of the present invention, the detection of the swelling ability of the bionic nucleus pulposus.

[0058] 1. Experimental method: The bionic nucleus pulposus is freeze-dried to determine its dry weight (Wd). Then the sample is immersed in distilled water at 37°C (simulating the physiological environment) to absorb water. And the swollen weight (Ws) is obtained by weighing the sample taken out of the water at each time point after water absorption and swelling. The mass swelling ratio is defined as: SRm = [(Ws - Wd) / Wd] × 100%.

[0059] 2. Experimental results: As Figure 12 shown, visually, the bionic nucleus pulposus of this example swells with time after being put into distilled water. The swollen body weight (Ws) is measured every hour until 10 hours after soaking. It can be seen that SRm increases sharply in the initial stage, that is, all samples quickly absorb water in the initial swelling stage, until the bionic nucleus pulposus has a high swelling ratio when the swelling equilibrium is finally reached.

[0060] Please refer to Figure 14As shown in the figure, this is Example 6 of the present invention, for detecting the self-healing performance of the bionic nucleus pulposus.

[0061] From Figure 14 It can be seen that the hydrogel of the present invention also has good self-healing performance. After being cut in half, it can still self-heal at the defect site to form a complete gel structure.

Claims

1. Self-healing bionic intervertebral disc capable of improving service stability, characterized in that: It includes an upper endplate (1), a bionic annulus fibrosus layer, a lower endplate (3), and a bionic nucleus pulposus (4). The bionic annulus fibrosus layer is sleeved outside the bionic nucleus pulposus (4), and the bionic annulus fibrosus layer and the bionic nucleus pulposus (4) are sandwiched between the upper endplate (1) and the lower endplate (3). Fixing teeth (5) are respectively arranged on the outer sides of the upper endplate (1) and the lower endplate (3).

2. The self-healing bionic intervertebral disc capable of improving service stability according to claim 1, wherein: The bionic annulus fibrosus layer described above includes a first annulus fibrosus layer (21), a second annulus fibrosus layer (22), a third annulus fibrosus layer (23), and a fourth annulus fibrosus layer (24). The first annulus fibrosus layer (21), the second annulus fibrosus layer (22), the third annulus fibrosus layer (23), and the fourth annulus fibrosus layer (24) are fixedly arranged in sequence from outside to inside; The first annulus fibrosus layer (21) includes a first annulus fibrosus matrix layer (211) and a first collagen fiber group. The first collagen fiber group is composed of several front-end first collagen fibers (2121) and several rear-end first collagen fibers (2122); both the front-end first collagen fibers (2121) and the rear-end first collagen fibers (2122) are arranged outside the first annulus fibrosus matrix layer (211). Several front-end first collagen fibers (2121) are arranged obliquely and parallelly, and several rear-end first collagen fibers (2122) are arranged obliquely and parallelly. After the first annulus fibrosus matrix layer (211) is unfolded, several front-end first collagen fibers (2121) and several rear-end first collagen fibers (2122) are all arranged parallelly on the same plane; The second annulus fibrosus layer (22) includes a second annulus fibrosus matrix layer (221) and a second collagen fiber group. The second collagen fiber group is composed of a front-end second collagen fiber (2221) and a rear-end second collagen fiber (2222); both the front-end second collagen fibers (2221) and the rear-end second collagen fibers (2222) are arranged outside the second annulus fibrosus matrix layer (221). Several front-end second collagen fibers (2221) are arranged obliquely and parallelly, and several rear-end second collagen fibers (2222) are arranged obliquely and parallelly. After the second annulus fibrosus matrix layer (221) is unfolded, several front-end second collagen fibers (2221) and several rear-end second collagen fibers (2222) are all arranged parallelly on the same plane, and the inclination directions of the front-end second collagen fibers (2221) and the rear-end second collagen fibers (2222) are opposite to the inclination directions of the front-end first collagen fibers (2121) and the rear-end first collagen fibers (2122); The third annulus fibrosus layer (23) includes a third annulus fibrosus matrix layer (231) and a third collagen fiber group, and the third collagen fiber group is composed of a front-end third collagen fiber (2321) and a rear-end third collagen fiber (2322); both the front-end third collagen fiber (2321) and the rear-end third collagen fiber (2322) are arranged on the outer side of the third annulus fibrosus matrix layer (231), a number of front-end third collagen fibers (2321) are arranged obliquely and parallelly, a number of rear-end third collagen fibers (2322) are arranged obliquely and parallelly, and after the third annulus fibrosus matrix layer (231) is unfolded, a number of front-end third collagen fibers (2321) and a number of rear-end third collagen fibers (2322) are arranged parallelly in the same plane, and the inclination directions of the front-end third collagen fiber (2321) and the rear-end third collagen fiber (2322) are the same as the inclination directions of the front-end first collagen fiber (2121) and the rear-end first collagen fiber (2122); The fourth annulus fibrosus layer (24) includes a fourth annulus fibrosus matrix layer (241) and a fourth collagen fiber group, and the fourth collagen fiber group is composed of a front-end fourth collagen fiber (2421) and a rear-end fourth collagen fiber (2422); both the front-end fourth collagen fiber (2421) and the rear-end fourth collagen fiber (2422) are arranged on the outer side of the fourth annulus fibrosus matrix layer (241), a number of front-end fourth collagen fibers (2421) are arranged obliquely and parallelly, a number of rear-end fourth collagen fibers (2422) are arranged obliquely and parallelly, and after the fourth annulus fibrosus matrix layer (241) is unfolded, a number of front-end fourth collagen fibers (2421) and a number of rear-end fourth collagen fibers (2422) are arranged parallelly in the same plane, and the inclination directions of the front-end fourth collagen fiber (2421) and the rear-end fourth collagen fiber (2422) are the same as the inclination directions of the front-end second collagen fiber (2221) and the rear-end second collagen fiber (2222).

3. The self-healing bionic intervertebral disc capable of improving service stability according to claim 2, wherein: The bionic annulus fibrosus layer is 3D integrally printed, and the first annulus fibrosus matrix layer (211), the second annulus fibrosus matrix layer (221), the third annulus fibrosus matrix layer (231) and the fourth annulus fibrosus matrix layer (241) are 3D printed with polyurethane materials with gradually decreasing hardness, and the first collagen fiber group, the second collagen fiber group, the third collagen fiber group and the fourth collagen fiber group are 3D printed with polyurethane resin.

4. The self-healing bionic intervertebral disc capable of enhancing service stability according to claim 2, characterized in that: The included angles formed by the first collagen fiber group, the second collagen fiber group, the third collagen fiber group and the fourth collagen fiber group with the surface of the upper end plate (1) increase in a gradient from the outside to the inside, and the gradient of the included angle is 5 degrees.

5. The self-healing bionic intervertebral disc capable of enhancing service stability according to claim 4, characterized in that: The included angle formed by the first collagen fiber group with the surface of the upper end plate (1) is 30 degrees, the included angle formed by the second collagen fiber group with the surface of the upper end plate (1) is 35 degrees, the included angle formed by the third collagen fiber group with the surface of the upper end plate (1) is 40 degrees, and the included angle formed by the fourth collagen fiber group with the surface of the upper end plate (1) is 45 degrees.

6. The self-healing bionic intervertebral disc capable of enhancing service stability according to claim 1, characterized in that: The cross-sections of the upper endplate (1), bionic annulus fibrosus layer, lower endplate (3), and bionic nucleus pulposus (4) are "D"-shaped; the materials of the upper endplate (1) and the lower endplate (3) are polyetheretherketone, and hydroxyapatite layers are plated on the outer surfaces of the upper endplate (1) and the lower endplate (3).

7. Preparation method of self-healing bionic intervertebral disc nucleus pulposus capable of improving service stability, characterized in that, It includes the following steps: Step 1: Under room temperature conditions, modify hyaluronic acid with sodium periodate to prepare sodium periodate-modified hyaluronic acid: Dissolve 2 g of sodium hyaluronate in 200 mL of distilled water, and stir under the condition of 200 revolutions per minute of a magnetic stirrer to fully dissolve sodium hyaluronate to obtain solution A; Then add sodium periodate to solution A so that the molar ratio of sodium periodate to sodium hyaluronate is 1:1, and stir for 24 hours under dark conditions to obtain solution B; Add 2 mL of ethylene glycol to solution B, react for 1 - 2 h to remove unreacted sodium periodate, and obtain solution C; Put the obtained solution C into a dialysis bag with a molecular weight cut-off of 10,000 - 16,000 and dialyze for 3 - 7 days, and then freeze-dry the dialyzed solution C to obtain sodium periodate-modified hyaluronic acid, that is, OHA. Among them, the molar ratio of hyaluronic acid to sodium periodate is 1:1, and the molecular weight of hyaluronic acid is 150,000 - 250,000; Step 2: Prepare a hydrogel polymer: Heat gelatin to 37 °C to successfully dissolve it into a gelatin solution; Take the OHA obtained in Step 1 and the above gelatin solution and dissolve them simultaneously in a 0.1 mol / L borax aqueous solution so that the mass concentration of OHA in the unit volume solution is 10% and the mass concentration of gelatin is 4%; Ultrasonically stir the above mixture for 2 minutes and then magnetically stir for 30 minutes to obtain a hydrogel polymer; Step 3: Finally, inject the above hydrogel polymer into a nucleus pulposus mold, and let it stand and cure at room temperature for 16 - 28 hours. After the hydrogel in-situ polymerizes and forms, an artificial nucleus pulposus prosthesis is obtained.

8. The preparation method of the self-healing bionic intervertebral disc nucleus pulposus capable of improving service stability according to claim 7, characterized in that: In Step 1, the dialysis time of solution C in the dialysis bag is 5 days, and the molecular weight cut-off of the used dialysis bag is 14,000.

9. The preparation method of the self-healing bionic intervertebral disc nucleus pulposus capable of improving service stability according to claim 7, characterized in that: The conditions of ultrasonic stirring in Step 2 are a power ratio of 100%, a closed temperature of 37 degrees Celsius, and a probe of 3 mm, and the conditions of magnetic stirring are 200 revolutions per minute of a magnetic stirrer.

10. The preparation method of the self-healing bionic intervertebral disc nucleus pulposus capable of enhancing service stability according to claim 7, wherein: In Step 3, the curing time of the hydrogel polymer in the nucleus pulposus mold is 24 hours.

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