CN117695443B - Negative poisson ratio structured artificial intervertebral disc and preparation method thereof - Google Patents
Negative poisson ratio structured artificial intervertebral disc and preparation method thereof Download PDFInfo
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Abstract
The invention belongs to the technical field of artificial intervertebral discs and discloses a negative poisson ratio structure artificial intervertebral disc and a preparation method thereof, wherein the artificial intervertebral disc is formed by combining an aldehyde group grafted round annular bracket with a negative poisson ratio structure, an aldehyde sodium alginate/gelatin composite hydrogel which is positioned in a central hole of the round annular bracket and coated on the surface of the round annular bracket through a chemical bond; the negative poisson ratio structural annular bracket grafted with aldehyde group is formed by sticking and sleeving a plurality of concentric annular plates with negative poisson ratio structures made of polycaprolactone and connecting the plates into a whole and then carrying out hydroformylation treatment. The artificial intervertebral disc overcomes the defects of the existing metal artificial intervertebral disc and artificial intervertebral disc with a positive poisson ratio structure, the stress strain trend of the artificial intervertebral disc accords with cartilage tissues, transverse shrinkage occurs when the artificial intervertebral disc is subjected to longitudinal compression load, and the hydroformylation sodium alginate/gelatin composite hydrogel has excellent compression resistance, high rebound resilience and fatigue resistance, and obviously improves the bonding strength with a bracket.
Description
Technical Field
The invention belongs to the technical field of artificial intervertebral discs, and particularly relates to an artificial intervertebral disc with a negative poisson ratio structure and a preparation method thereof.
Background
The intervertebral disc is cartilage tissue connecting adjacent vertebral bodies of the spine, and consists of a central gelatinous nucleus pulposus and peripheral fibrous rings, and can disperse spinal load to maintain the stable state of the spine. Intervertebral disc disease, particularly herniated disc, is one of the most common spinal disorders in modern society, statistically affecting millions of adults worldwide, becoming an important factor leading to loss of work capacity and reduced quality of life. Herniated discs occur primarily in the lumbar and cervical regions, due to degeneration, injury or wear of the disc. With age, the intervertebral disc gradually loses water and becomes weaker, and the outer annulus fibrosus is prone to crack, thereby causing herniated nucleus pulposus tissue inside the intervertebral disc, compressing nearby nerve roots or spinal cord. In many cases, the treatment of herniated disc includes physical therapy, medication, and lifestyle modification. However, for some patients, conservative treatment may not provide long-term relief, particularly in cases where neurological symptoms are evident or spinal stability is compromised. Therefore, under the condition of failure of conservation treatment, the intervertebral disc operation is a comparatively ideal treatment mode, wherein the artificial intervertebral disc replacement operation is an operation mode with definite effect.
In clinic, the artificial intervertebral disc for the intervertebral disc replacement operation is usually a metal intervertebral disc, and the artificial intervertebral disc has stable chemical properties, but because of the lack of high elasticity, the compressive load borne by the human spine cannot be sufficiently buffered, and long-term diseases of adjacent segments can be caused, including degeneration of vertebral bodies, formation of new bone neoplasms, protrusion of intervertebral discs and the like. In addition, metal implants have not been able to fully restore normal physiological motor function to the spine.
Since the above-mentioned problems exist in the metallic artificial intervertebral disc, the study of the nonmetallic artificial intervertebral disc is increasingly being paid attention to and developed, for example, bioactive Materials discloses a 3D bioprinting dual growth factor releasing intervertebral disc scaffold [ see Bioactive materials, volume 6, phase 1 (2021) 179-190 ], whose Nucleus Pulposus (NP) and Annulus Fibrosus (AF) are printed with 3D bioprinting ink formed by mixing ctgf@pda NPs (or TGF- β3@pda NPs), bone marrow mesenchymal stem cells and hydrogel. Nanoscale discloses a tissue engineering intervertebral disc scaffold constructed by bionic nanofibers (see nanoscales, volume 35, ninth stage (2017) 13095-13103), which is formed by combining an electrospun scaffold with concentric rings of type I collagen and alginate hydrogel. However, these artificial intervertebral discs are all designed in a traditional positive poisson ratio structure, and because the positive poisson ratio material expands transversely when being subjected to a longitudinal compressive load, the artificial intervertebral disc with the structural design collapses after being implanted into a body for a period of time, and even the inner nucleus pulposus is damaged by extrusion.
Disclosure of Invention
The invention aims to overcome the defects of the prior art and provide an artificial intervertebral disc with a negative poisson ratio structure and a preparation method thereof, so that the artificial intervertebral disc with biocompatibility and stable mechanical property can be obtained, and the preparation process is simplified.
The artificial intervertebral disc with the negative poisson ratio structure is formed by combining an annular bracket with the negative poisson ratio structure and grafted aldehyde groups with aldehyde sodium alginate/gelatin composite hydrogel which is positioned in a central hole of the annular bracket and coated on the surface of the annular bracket through chemical bonds; the negative poisson ratio structural annular bracket grafted with aldehyde group is formed by sticking and sleeving a plurality of concentric annular plates with negative poisson ratio structures made of polycaprolactone and connecting the plates into a whole and then carrying out hydroformylation treatment.
The negative poisson ratio structure comprises a concave structure, a chiral structure, a rotary polygonal structure, a paper folding structure, a perforated plate structure and a sheet fold structure. The concave structure is a commonly used negative poisson ratio structure. The negative poisson ratio material can generate transverse shrinkage deformation when axially compressed, and can generate longitudinal compression to form transverse shrinkage when impacted by an object, and the material near the contact point converges towards the object so as to increase the local density of the contact point and generate densification, thereby increasing the indentation resistance of the material and being difficult to generate indentation.
In the artificial intervertebral disc with the negative poisson ratio structure, the thickness of the concentric circular ring sheets with the negative poisson ratio structure, which are made of polycaprolactone, is 2 mm-2.5 mm, and the number of the concentric circular ring sheets is 5-6.
In the artificial intervertebral disc with the negative poisson ratio structure, a plurality of concentric circular plates with the negative poisson ratio structure, which are made of polycaprolactone, are sleeved and connected into an integrated circular bracket with the negative poisson ratio structure, and the outer diameter, the aperture of the central hole and the height of the circular bracket are determined according to the size of the intervertebral disc of a patient.
In the artificial intervertebral disc with the negative poisson ratio structure, the annular bracket with the negative poisson ratio structure, the surface of which is coated with the sodium alginate/gelatin composite hydrogel, corresponds to the Annulus Fibrosus (AF) of the intervertebral disc, and the sodium alginate/gelatin composite hydrogel positioned in the central hole of the annular bracket corresponds to the Nucleus Pulposus (NP) of the intervertebral disc.
The preparation method of the artificial intervertebral disc with the negative poisson ratio structure comprises the following steps:
(1) Preparing a ring-shaped bracket with a negative poisson ratio structure;
Taking polycaprolactone powder as a raw material, and obtaining a plurality of concentric circular plates with a negative poisson ratio structure, which are made of polycaprolactone, through 3D printing, wherein the concentric circular plates are sleeved and connected into an integrated circular bracket with the negative poisson ratio structure;
(2) Carrying out hydroformylation treatment on the annular bracket with the negative poisson ratio structure;
Dissolving 1, 6-hexamethylenediamine in isopropanol to prepare a1, 6-hexamethylenediamine isopropanol solution with the mass concentration of 10%, soaking the circular bracket with the negative poisson ratio structure prepared in the step (1) in the 1, 6-hexamethylenediamine isopropanol solution, magnetically stirring for 10-12 hours at room temperature, ultrasonically cleaning with deionized water to remove unreacted 1, 6-hexamethylenediamine, and then placing the bracket into a vacuum drying oven to be dried for 10-12 hours at 37 ℃ to obtain an ammonolysis bracket;
Placing the ammonolysis bracket into glutaraldehyde water solution with the mass concentration of 2% for soaking for 10-12 h at room temperature, then using deionized water for ultrasonic cleaning to remove unreacted glutaraldehyde, and then placing the ammonolysis bracket into a vacuum drying oven for drying for 20-24 h at 37 ℃ to obtain the grafted aldehyde-based annular bracket with the negative poisson ratio structure;
(3) Preparing aldehyde sodium alginate/gelatin composite hydrogel;
sodium alginate is dissolved in absolute ethyl alcohol to prepare sodium alginate ethanol solution with the concentration of 0.2g/mL, sodium periodate serving as an oxidant is dissolved in deionized water to prepare sodium periodate aqueous solution with the concentration of 0.1 g/mL-0.12 g/mL, and the sodium alginate ethanol solution and the sodium periodate aqueous solution are mixed according to the volume ratio of 1: 9-10 metering, adding the metered sodium periodate aqueous solution into the sodium alginate ethanol solution under stirring, continuously stirring for 6-8 hours in a light-shielding environment to obtain a reaction solution, centrifuging the reaction solution, collecting a precipitate, repeatedly centrifuging and washing with absolute ethanol to remove unreacted sodium periodate, and freeze-drying to obtain aldehyde sodium alginate powder;
Dissolving aldehyde sodium alginate powder and borax in deionized water at 37 ℃ to prepare a mixed solution with the mass concentration of the aldehyde sodium alginate of 4% and the mass concentration of the borax of 2%, dissolving gelatin in deionized water at 50-55 ℃ to prepare a gelatin aqueous solution with the mass concentration of 12%, and preparing a gelatin-containing aqueous solution and the aldehyde sodium alginate contained in the mixed solution into a gelatin-containing aqueous solution with the mass ratio of 1: 1-3, metering a gelatin aqueous solution and a mixed solution, adding the gelatin aqueous solution into the mixed solution under stirring, uniformly mixing, standing at 37 ℃ for 6-8 hours, and standing at room temperature for 20-24 hours to obtain an aldehyde sodium alginate/gelatin composite hydrogel;
(4) Forming an artificial intervertebral disc with a negative poisson ratio structure;
Placing the negative poisson ratio structural circular support grafted with the aldehyde group in an aldehyde sodium alginate/gelatin composite hydrogel, standing for 6-8 hours at 37 ℃, and then standing for 20-24 hours at room temperature, wherein in the process, the aldehyde sodium alginate/gelatin composite hydrogel enters a central hole of the negative poisson ratio structural circular support grafted with the aldehyde group and coats the surface of the central hole, and amino in the aldehyde sodium alginate/gelatin composite hydrogel reacts with aldehyde groups on the negative poisson ratio structural circular support grafted with the aldehyde group to form an imine bond to realize chemical bond bonding, so that the artificial intervertebral disc with the negative poisson ratio structure is formed.
In the method, the freeze-drying temperature in the step (3) is-50 ℃ to-80 ℃ and the time is 24h to 26 h.
The artificial intervertebral disc overcomes the defects of the existing metal artificial intervertebral disc and artificial intervertebral disc with a positive poisson ratio structure, the stress strain trend of the artificial intervertebral disc accords with cartilage tissues, transverse shrinkage occurs when the artificial intervertebral disc is subjected to longitudinal compression load, and the hydroformylation sodium alginate/gelatin composite hydrogel has excellent compression resistance, high rebound resilience and fatigue resistance, and obviously improves the bonding strength with a bracket.
The invention has the following beneficial effects:
1. Since the aldehyde sodium alginate/gelatin composite hydrogel of the present invention is formed by bonding gelatin and aldehyde sodium alginate through imine bond, it has excellent compression resistance, high rebound resilience and fatigue resistance (see example 2).
2. Experiments show that the aldehyde sodium alginate/gelatin composite hydrogel prepared by the method and the artificial intervertebral disc with the negative poisson ratio structure have good biocompatibility (see example 2).
3. The artificial intervertebral disc with the negative poisson ratio structure is formed by combining the annular bracket with the negative poisson ratio structure grafted with aldehyde groups and the aldehyde sodium alginate/gelatin composite hydrogel which is positioned in the central hole of the annular bracket and coated on the surface of the annular bracket through chemical bonds, so that the artificial intervertebral disc has the viscoelasticity consistent with that of the composite hydrogel, accords with the stress strain trend of cartilage tissues, has the rigidity of 3.87+/-0.75 MPa, is equivalent to the mechanical requirement of the intervertebral disc, can transversely shrink when being subjected to longitudinal compression load, has obviously improved bonding strength of the composite hydrogel and the bracket, and can effectively avoid the problem of split phase of physical bonding under the load.
4. The artificial intervertebral disc with the negative poisson ratio structure has excellent mechanical property and biocompatibility, and the composite hydrogel has good bonding strength with the bracket, so that the artificial intervertebral disc with the negative poisson ratio structure can obtain good treatment effect by replacing the degenerated intervertebral disc.
5. The method has the advantages of easily obtained raw materials, simple preparation process, convenient operation and favorable implementation and application.
Drawings
Fig. 1 is a schematic diagram of a negative poisson's ratio structural torus according to the present invention.
Fig. 2 is an enlarged view of the negative poisson's ratio structure on the torus plate of fig. 1.
Fig. 3 is a schematic diagram of a negative poisson's ratio structural toroidal stent made from polycaprolactone in the present invention, wherein H represents the height of the negative poisson's ratio structural toroidal stent.
Fig. 4 is a top view of fig. 3, wherein D represents the aperture of the central bore of the negative poisson's ratio structural toroidal support and D represents the outer diameter of the negative poisson's ratio structural toroidal support.
Fig. 5 is a schematic diagram of an artificial intervertebral disc of the negative poisson's ratio configuration according to the invention.
Fig. 6 is a top view of fig. 5.
FIG. 7 is a graph showing the first cycle curve and the second cycle curve of the test of the cyclic compression of the formylated sodium alginate/gelatin composite hydrogel A1G2 prepared in example 1 of the present invention.
FIG. 8 is a morphology chart of the aldehyde sodium alginate/gelatin composite hydrogel A1G2 prepared in example 1 of the present invention after 8 cyclic compression test cyclic loading.
Fig. 9 is a graph of compression test of the negative poisson's ratio structural annular stent-vPCL, the aldehyde sodium alginate/gelatin composite hydrogel A1G2 and the negative poisson's ratio structural artificial intervertebral disc-vPCL-A1G 2 prepared in example 1 of the present invention, wherein (a) is a compressive stress strain curve, and (b) is a compressive elastic modulus schematic diagram.
FIG. 10 is a graph showing the cell compatibility test of the negative Poisson's ratio structural circular scaffold-vPCL-GA, the formylated sodium alginate/gelatin composite hydrogel A1G2 and the negative Poisson's ratio structural artificial intervertebral disc-vPCL-A1G 2 of the grafted aldehyde group prepared in example 1 of the present invention, wherein (a) is a staining fluorescence chart of rat Nucleus Pulposus (NP) cells after co-culturing for 1, 3 and 5 days, (b) is a living cell count result chart, and (c) is a graph showing the detection of cell proliferation by CCK-8 method.
In the figure, the ring-shaped bracket with the 1-negative poisson ratio structure, 1-concentric ring-shaped sheets, 1-2-connecting strips, 2-aldehyde sodium alginate/gelatin composite hydrogel positioned in the central hole of the ring-shaped bracket and 3-aldehyde sodium alginate/gelatin composite hydrogel coated on the surface of the ring-shaped bracket.
Detailed Description
The artificial intervertebral disc with the negative poisson ratio structure and the preparation method thereof are further described below by way of examples and with reference to the accompanying drawings.
In the following examples, polycaprolactone (PCL) powder was purchased from Shenzhen easy to grow industries, inc., china, sodium alginate and gelatin were purchased from Shanghai Aba Ding Shenghua technologies, inc., sodium periodate and borax were purchased from Chengdu Jinshan chemical reagent, inc., and other chemical reagents were all purchased through the market.
Example 1
The artificial intervertebral disc with the negative poisson ratio structure in the embodiment is formed by combining an aldehyde group grafted annular bracket 1 with the negative poisson ratio structure, an aldehyde sodium alginate/gelatin composite hydrogel 2 positioned in the central hole of the annular bracket and an aldehyde sodium alginate/gelatin composite hydrogel 3 coated on the surface of the annular bracket through chemical bonds as shown in fig. 5 and 6; the negative poisson ratio structural annular bracket 1 grafted with the aldehyde group is formed by pasting and sleeving five concentric annular plates 1-1 with the negative poisson ratio structural made of polycaprolactone and connecting the plates into a whole by connecting strips 1-2 and then carrying out hydroformylation treatment; the thicknesses of the five concentric circular plates with the negative poisson ratio structure are the same and are all 2mm, the outer diameter D of the circular support 1 with the negative poisson ratio structure is 4cm, the aperture D of the central hole is 2cm, and the height H is 1.2cm.
The preparation method of the artificial intervertebral disc with the negative poisson ratio structure comprises the following steps:
(1) Preparing a ring-shaped bracket with a negative poisson ratio structure;
Taking polycaprolactone powder as a raw material, and according to the structural design, obtaining five concentric circular plates with negative poisson ratio structures, which are made of polycaprolactone, through 3D printing, wherein the circular plates with the negative poisson ratio structures are sleeved and connected into a whole, namely, a circular bracket (named as a-vPCL bracket), and the circular plates with the negative poisson ratio structures are shown in fig. 3 and 4, the circular plates with the negative poisson ratio structures are shown in fig. 1, and the circular plates with the negative poisson ratio structures are shown in fig. 2 and are of a concave structure;
(2) Carrying out hydroformylation treatment on the annular bracket with the negative poisson ratio structure;
Dissolving 1, 6-hexamethylenediamine in isopropanol to prepare a1, 6-hexamethylenediamine isopropanol solution with the mass concentration of 10%, soaking the circular bracket with the negative poisson ratio structure prepared in the step (1) in the 1, 6-hexamethylenediamine isopropanol solution, magnetically stirring for 12 hours at room temperature, then ultrasonically cleaning with deionized water to remove unreacted 1, 6-hexamethylenediamine, and then drying in a vacuum drying oven at 37 ℃ for 12 hours to obtain the ammonolysis bracket
Placing the ammonolysis bracket into glutaraldehyde water solution with the mass concentration of 2% to soak for 12h at room temperature, then using deionized water to ultrasonically clean and remove unreacted glutaraldehyde, and then placing the ammonolysis bracket into a vacuum drying oven to dry for 24 hours at 37 ℃ to obtain a negative poisson ratio structural annular bracket (named as-vPCL-GA bracket) grafted with aldehyde groups;
(3) Preparing aldehyde sodium alginate/gelatin composite hydrogel;
Sodium alginate is dissolved in absolute ethyl alcohol to prepare sodium alginate ethanol solution with the concentration of 0.2g/mL, oxidant sodium periodate is dissolved in deionized water to prepare sodium periodate water solution with the concentration of 0.1g/mL, and the volume ratio of the sodium alginate ethanol solution to the sodium periodate water solution is 1: 10. metering, adding the metered sodium periodate aqueous solution into the sodium alginate ethanol solution under stirring, continuously stirring in a light-shielding environment for 6 hours to obtain a reaction solution, centrifuging the reaction solution, collecting a precipitate, repeatedly centrifuging and washing with absolute ethanol for three times to remove unreacted sodium periodate, and freeze-drying at-80 ℃ for 24 hours to obtain aldehyde sodium alginate powder;
Dissolving aldehyde sodium alginate powder and borax in deionized water at 37 ℃ to prepare a mixed solution with the mass concentration of the aldehyde sodium alginate of 4% and the mass concentration of the borax of 2%, dissolving gelatin in deionized water at 50 ℃ to prepare a gelatin aqueous solution with the mass concentration of 12%, and preparing the mixture of the gelatin aqueous solution and the aldehyde sodium alginate of 1:2, metering gelatin aqueous solution and mixed solution, adding the gelatin aqueous solution into the mixed solution under stirring, uniformly mixing, standing at 37 ℃ for 6 hours, and standing at room temperature for 24 h to obtain aldehyde sodium alginate/gelatin composite hydrogel (named A1G 2);
(4) Forming an artificial intervertebral disc with a negative poisson ratio structure;
Placing the negative poisson ratio structural circular support grafted with the aldehyde group in an aldehyde sodium alginate/gelatin composite hydrogel, standing for 6 hours at 37 ℃ and then standing for 24h at room temperature, wherein in the process, the aldehyde sodium alginate/gelatin composite hydrogel enters a central hole of the negative poisson ratio structural circular support grafted with the aldehyde group and coats the surface of the central hole, and amino in the aldehyde sodium alginate/gelatin composite hydrogel reacts with aldehyde groups on the negative poisson ratio structural circular support grafted with the aldehyde group to form an imine bond to realize chemical bond bonding, so that the artificial intervertebral disc (named-vPCL-A1G 2) with the negative poisson ratio structure is formed.
Example 2
1. Mechanical property test
Mechanical properties test according to ISO 844:2004, a universal mechanical tester (SHIMADZU, AG-IC 50K Japan) was used, the compression speed being set at 2 mm/min.
(1) The aldehyde sodium alginate/gelatin composite hydrogel A1G2 prepared in the step (3) of the example 1 is subjected to cyclic compression test, and the specific operation is as follows: the test samples were loaded to 80% strain and unloaded to 0% and cycled 8 times. The test results are shown in fig. 7 and 8.
As can be seen from fig. 7, the first cycle curve and the second cycle curve are well closed, indicating that the aldehyde sodium alginate/gelatin composite hydrogel prepared in example 1 has excellent anti-fatigue properties.
From fig. 8, it can be seen that the experimental sample maintains the complete morphology after 8 times of cyclic loading, which indicates that the aldehyde sodium alginate/gelatin composite hydrogel prepared in example 1 has excellent compression resistance.
(2) Compression tests are carried out on the annular bracket with the negative poisson ratio structure prepared in the step (1) in the example 1, the aldehyde sodium alginate/gelatin composite hydrogel A1G2 prepared in the step (3) and the artificial intervertebral disc with the negative poisson ratio structure prepared in the step (4), wherein the test results are shown in figure 9.
As can be seen from fig. 9 (a), the compressive stress strain curve corresponding to the artificial intervertebral disc-vPCL-A1G 2 has a change trend between the support-vPCL and the composite hydrogel A1G2, and the artificial intervertebral disc-vPCL-A1G 2 exhibits a viscoelastic behavior consistent with the composite hydrogel due to the introduction of the composite hydrogel, and conforms to the stress strain trend of cartilage tissue; when the compression of the experimental sample reaches 40% deformation, the compression strength of the artificial intervertebral disc-vPCL-A1G 2 is obviously higher than that of the composite hydrogel A1G2 glue, but lower than that of the support-vPCL, because the upper end and the lower end of the artificial intervertebral disc-vPCL-A1G 2 are covered by the composite hydrogel, a buffer effect is achieved, when the stress is just applied, the composite hydrogel covered by the upper end and the lower end of the artificial intervertebral disc-vPCL-A1G 2 can be deformed to a larger extent first, and then the covered support is driven to deform together, so that the stress is hardly changed in the initial 10% strain stage in the compression process of the artificial intervertebral disc-vPCL-A1G 2, and the stress is greatly increased after the strain reaches 20%.
As can be seen from FIG. 9 (b), the artificial intervertebral disc-vPCL-A1G 2 has a lower compressive modulus than the scaffold-vPCL, but is significantly stronger than the composite hydrogel A1G2. It is worth emphasizing that the rigidity of the artificial intervertebral disc-vPCL-A1G 2 reaches 3.87+/-0.75 MPa, which is equivalent to the strict mechanical requirements of natural fibrocartilage such as intervertebral discs and the like.
2. In vitro cell experiments
(1) Cell extraction and culture
The experimental animals were male SD rats (6-8 weeks old, 200-250 g) purchased from Chengdu animal experiment animal Co., ltd.
Male SD rats were euthanized with an excess of 10% chloral hydrate. The lumbar segment and lumbar disc were isolated under sterile conditions, nucleus pulposus tissue was removed with micropunches, then digested 30 min in 0.25% strength by mass trypsin solution at 37 ℃, then transferred into 0.1% strength by mass type II collagenase and digested 4 h by shaking at 37 ℃. The resulting suspension was centrifuged at 1000 rpm for 5 min, and the pellet was resuspended in α -MEM containing 10% by mass PBS and 1% by mass penicillin/streptomycin and incubated in a 5% by volume CO 2 incubator at 37 ℃ and replaced once every other day. When the bottom area of the culture flask is over 80 percent, the culture medium is sucked away, the nucleus pulposus cells are washed by PBS buffer solution, trypsin is added, and the nucleus pulposus cells are placed into an incubator for incubation 2 min. After digestion is completed, adding a culture medium to stop digestion and blowing and dispersing the cell suspension uniformly, wherein the ratio of the culture medium to the cell suspension is 1: 2. the third generation rat nucleus pulposus cells were taken for subsequent experiments.
(2) Cell compatibility experiments
The negative poisson ratio structural annular bracket-vPCL-GA of the grafted aldehyde group prepared in the step (2) of the example 1, the aldehyde sodium alginate/gelatin composite hydrogel A1G2 prepared in the step (3) and the negative poisson ratio structural artificial intervertebral disc-vPCL-A1G 2 prepared in the step (4) are sterilized by ultraviolet irradiation and then placed in a 48-pore plate, the third-generation rat Nucleus Pulposus (NP) cells are respectively inoculated on the experimental samples at the density of 2X 10 5 cells/pore, and placed in a constant temperature incubator (37 ℃, 5v percent CO 2) for culture, and liquid exchange is carried out every other day. After co-culturing rat Nucleus Pulposus (NP) cells with experimental samples for 1, 3, 5 days, respectively, the cells were stained with a Live/dead cell staining kit (Live/DEAD STAINING, kaiki biosciences, china) and the Live/dead cell morphology was observed under an inverted fluorescent microscope (Olympus IX83, japan). Proliferation of cells on the experimental samples was determined by CCK-8 kit (Kaiki Bio Inc., china). After 1, 3, 5 days of culture of rat Nucleus Pulposus (NP) cells on the experimental samples, the medium was aspirated, a 10% strength by mass CCK-8 solution prepared by adding the medium to each well was incubated at 37℃in an incubator with 5v.% CO 2 for 2h, 100. Mu.L of the supernatant was transferred to a 96-well plate, and absorbance was measured at 450 nm wavelength using an enzyme-labeled instrument (BioTek, USA). Rat Nucleus Pulposus (NP) cells cultured on cell culture plates were used as a blank control and were designated NC group. The experimental results are shown in FIG. 10.
As can be seen from FIG. 10 (a), compared with the control group, the cells co-cultured by the composite hydrogel A1G2, the scaffold-vPCL-GA and the artificial intervertebral disc-vPCL-A1G 2 all show stronger cell activity, full cell morphology and spindle morphology, and the cells are connected with each other through the stretched pseudopoda, so that the components of the three groups of samples have no obvious cytotoxicity and no dead cells.
As can be seen from fig. 10 (b), there was no significant difference in the number of living cells at different time points between the three samples and the control NC.
As can be seen from fig. 10 (c), the proliferation levels of the cells in the composite hydrogel A1G2 and the artificial intervertebral disc-vPCL-A1G 2 were close, and showed no significant difference compared to the control NC, indicating that the composite hydrogel A1G2, the scaffold-vPCL-GA and the artificial intervertebral disc-vPCL-A1G 2 were excellent in cell proliferation on days 1,3, 5.
Claims (3)
1. The artificial intervertebral disc with the negative poisson ratio structure is characterized by being formed by combining an annular bracket with the negative poisson ratio structure and grafted with aldehyde groups with aldehyde sodium alginate/gelatin composite hydrogel which is positioned in a central hole of the annular bracket and coated on the surface of the annular bracket through chemical bonds; the negative poisson ratio structural annular bracket grafted with aldehyde group is formed by sticking and sleeving a plurality of concentric annular plates with negative poisson ratio structures made of polycaprolactone and connecting the plates into a whole and then carrying out hydroformylation treatment.
2. The artificial intervertebral disc with the negative poisson ratio structure according to claim 1 is characterized in that the thickness of the concentric circular ring plates with the negative poisson ratio structure made of polycaprolactone is 2 mm-2.5 mm, and the number of the concentric circular ring plates is 5-6.
3. A method for preparing an artificial intervertebral disc with a negative poisson's ratio structure according to claim 1 or 2, which is characterized by comprising the following steps:
(1) Preparing a ring-shaped bracket with a negative poisson ratio structure;
Taking polycaprolactone powder as a raw material, and obtaining a plurality of concentric circular plates with a negative poisson ratio structure, which are made of polycaprolactone, through 3D printing, wherein the concentric circular plates are sleeved and connected into an integrated circular bracket with the negative poisson ratio structure;
(2) Carrying out hydroformylation treatment on the annular bracket with the negative poisson ratio structure;
Dissolving 1, 6-hexamethylenediamine in isopropanol to prepare a1, 6-hexamethylenediamine isopropanol solution with the mass concentration of 10%, soaking the circular bracket with the negative poisson ratio structure prepared in the step (1) in the 1, 6-hexamethylenediamine isopropanol solution, magnetically stirring for 10-12 hours at room temperature, ultrasonically cleaning with deionized water to remove unreacted 1, 6-hexamethylenediamine, and then placing the bracket into a vacuum drying oven to be dried for 10-12 hours at 37 ℃ to obtain an ammonolysis bracket;
Placing the ammonolysis bracket into glutaraldehyde water solution with the mass concentration of 2% for soaking for 10-12 h at room temperature, then using deionized water for ultrasonic cleaning to remove unreacted glutaraldehyde, and then placing the ammonolysis bracket into a vacuum drying oven for drying for 20-24 h at 37 ℃ to obtain the grafted aldehyde-based annular bracket with the negative poisson ratio structure;
(3) Preparing aldehyde sodium alginate/gelatin composite hydrogel;
sodium alginate is dissolved in absolute ethyl alcohol to prepare sodium alginate ethanol solution with the concentration of 0.2g/mL, sodium periodate serving as an oxidant is dissolved in deionized water to prepare sodium periodate aqueous solution with the concentration of 0.1 g/mL-0.12 g/mL, and the sodium alginate ethanol solution and the sodium periodate aqueous solution are mixed according to the volume ratio of 1: 9-10 metering, adding the metered sodium periodate aqueous solution into the sodium alginate ethanol solution under stirring, continuously stirring for 6-8 hours in a light-shielding environment to obtain a reaction solution, centrifuging the reaction solution, collecting a precipitate, repeatedly centrifuging and washing with absolute ethanol to remove unreacted sodium periodate, and freeze-drying to obtain aldehyde sodium alginate powder;
Dissolving aldehyde sodium alginate powder and borax in deionized water at 37 ℃ to prepare a mixed solution with the mass concentration of the aldehyde sodium alginate of 4% and the mass concentration of the borax of 2%, dissolving gelatin in deionized water at 50-55 ℃ to prepare a gelatin aqueous solution with the mass concentration of 12%, and preparing a gelatin-containing aqueous solution and the aldehyde sodium alginate contained in the mixed solution into a gelatin-containing aqueous solution with the mass ratio of 1: 1-3, metering a gelatin aqueous solution and a mixed solution, adding the gelatin aqueous solution into the mixed solution under stirring, uniformly mixing, standing at 37 ℃ for 6-8 hours, and standing at room temperature for 20-24 hours to obtain an aldehyde sodium alginate/gelatin composite hydrogel;
(4) Forming an artificial intervertebral disc with a negative poisson ratio structure;
Placing the negative poisson ratio structural circular support grafted with the aldehyde group in an aldehyde sodium alginate/gelatin composite hydrogel, standing for 6-8 hours at 37 ℃, and then standing for 20-24 hours at room temperature, wherein in the process, the aldehyde sodium alginate/gelatin composite hydrogel enters a central hole of the negative poisson ratio structural circular support grafted with the aldehyde group and coats the surface of the central hole, and amino in the aldehyde sodium alginate/gelatin composite hydrogel reacts with aldehyde groups on the negative poisson ratio structural circular support grafted with the aldehyde group to form an imine bond to realize chemical bond bonding, so that the artificial intervertebral disc with the negative poisson ratio structure is formed.
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