Device for degeneration of rat caudal vertebra intervertebral disc

Abstract

The invention discloses a device for rat caudal vertebra intervertebral disc degeneration. The device comprises a fixing unit and a loading unit. The fixing unit comprises two metal rings which are respectively fixed on adjacent vertebral bodies on the upper side and the lower side of a target intervertebral disc; at least two nails used for being implanted into a vertebral body are arranged on the circumference of the inner side of each metal ring; a plurality of hooks are arranged on the circumference of the outer side of each metal ring; the loading unit comprises at least two hook springs, and the two ends of the hook springs are detachably connected to the hooks at the specific positions of the upper metal ring and the lower metal ring. Through the combination of the angle of the hook and the rigidity of the spring, complex multi-dimensional mechanical loads borne by the spine in the physiological or pathological state can be simulated, the loads are not only pressure in the single direction and are closer to the actual stress condition of the intervertebral disc of the human body, the angle position of the hook is fixed, and the rigidity of the spring is known; this allows the applied load to be accurately calculated and repeated.

Description

TECHNICAL FIELD

[0001] The present application relates to the technical field of rat tail vertebra intervertebral disc degeneration, and particularly relates to a device for rat tail vertebra intervertebral disc degeneration. BACKGROUND

[0002] Intervertebral disc degeneration is the main pathological basis of many spinal diseases such as low back pain, and its etiology and pathogenesis are not fully clear. Research shows that abnormal mechanical load is one of the key factors leading to intervertebral disc degeneration. In order to further study the mechanism of intervertebral disc degeneration, it is crucial to construct an experimental model that can simulate the in vivo mechanical environment. The commonly used intervertebral disc degeneration models currently include animal models (such as rats, mice, rabbits, sheep, etc.) and in vitro culture models. In terms of animal models, the existing technology mainly uses devices such as needle puncture annulus fibrosus, enzymatic nucleus pulposus, or surgical changes in spinal stability to induce degeneration. However, these devices have obvious limitations: the damage caused by needle puncture or enzymatic method is a one-time and uncontrollable mechanical or chemical damage, which is difficult to accurately simulate the complex and continuous mechanical stimulation under physiological or pathological conditions. The device that changes the stability of the spine through surgery has the problems of long modeling period, large individual difference, and poor repeatability. In addition, some models that apply axial pressure by fixing the animal's tail can simulate certain mechanical environment, but their loading means are single and it is difficult to simulate complex multi-dimensional mechanical states, such as controlling the ratio of pressure and torsion at the same time. In terms of in vitro models, existing technology has developed bioreactors that can perform certain mechanical loading, such as devices that can be axially pressed (continuously or periodically) or devices assisted by a liquid flow system. However, these devices often focus on axial pressure on the intervertebral disc, making it difficult to well simulate complex stress states such as overextension, overflexion, lateral bending, and rotation. In addition, existing devices still have deficiencies in adapting to different sizes of intervertebral discs and achieving flexible and accurate adjustment of loading parameters. Therefore, there is an urgent need in the field for an intervertebral disc degeneration model device that can accurately control and flexibly adjust multiple mechanical loading parameters, thereby better simulating the complex in vivo mechanical environment and being applicable to in vivo animal experiments. SUMMARY

[0003] The purpose of the present application is to solve the problems existing in the prior art and provide a device for rat tail vertebra intervertebral disc degeneration.

[0004] To achieve the above purpose, the technical scheme adopted by the present application is as follows: A device for rat tail vertebra intervertebral disc degeneration, comprising: Two fixed units: respectively used for fixing the adjacent vertebral bodies on the upper and lower sides of the target intervertebral disc; A loading unit is arranged between the two fixed units. The loading unit comprises a plurality of hooks arranged on the outer circumference of the metal ring and hook springs connected between the hooks, two ends of the hook springs being connected to the hooks at different positions on the two metal rings to exert adjustable compound loads on the intervertebral disc.

[0005] As a further scheme of the present application, each of the fixing units comprises a metal ring and at least two nail members arranged on the inner circumference of the metal ring and capable of penetrating the cortical bone of the vertebral body to anchor the metal ring on the vertebral body during implantation.

[0006] As a further scheme of the present application, the nail members comprise a cortical bone nail and a nail head which are integrally formed, and the inner wall of the circumference of the metal ring is provided with a socket matched with the cortical bone nail.

[0007] As a further scheme of the present application, a plurality of groups of hooks are arranged on each of the metal rings and are distributed at equal intervals along the circumference.

[0008] As a further scheme of the present application, the two ends of the hook springs are provided with hook-shaped or ring-shaped structures for being hung on the hooks.

[0009] As a further scheme of the present application, the hook springs can be selected in terms of the stiffness coefficient k, and the size of the exerted force is controlled by replacing the hook springs with different stiffness coefficients.

[0010] As a further scheme of the present application, the hook springs simulate single or compound mechanical environments in the states of forward flexion, backward extension, lateral flexion or rotation through different connection combinations.

[0011] As a further scheme of the present application, a plurality of the hook springs are used in combination, and the proportions and directions of the axial force, lateral force and torsional force exerted on the intervertebral disc are adjusted by connecting the hook springs between the hooks at different circumferential positions on the two metal rings.

[0012] As a further scheme of the present application, the two ends of the hook springs are hung on the hooks at different circumferential positions on the two metal rings to change the direction of the action line of the load, and compound loads containing torsional components are exerted on the intervertebral disc.

[0013] As a further scheme of the present application, the metal ring is made of medical stainless steel or titanium alloy material.

[0014] Compared with the prior art, the present application provides a device for rat tail intervertebral disc degeneration, which has the following beneficial effects: 1. Through the combination of hook angles and spring stiffness, complex multi-dimensional mechanical loads borne by the spine in physiological or pathological states can be simulated, not only single-directional pressure, and the actual stress condition of the human intervertebral disc is closer.

[0015] 2. The angle position of the hook is fixed, and the stiffness of the spring is known, which makes the applied load can be accurately calculated and repeated, greatly improving the scientificity and repeatability of the experiment, overcoming the randomness and unquantifiability of traditional methods (such as needle puncture).

[0016] 3. Only need to change the connection position or type of the spring, the rapid switching of multiple different mechanical stimulation modes can be realized on the same device, which provides great convenience for studying the effects of different mechanical factors on intervertebral disc degeneration without changing complex components.

[0017] 4. The device has compact structure and is fixed and reliable, has relatively small influence on normal activity of animals, allows long-term mechanical stimulation, and is helpful for studying the chronic and progressive process of intervertebral disc degeneration, and is superior to in vitro models.

[0018] 5. Compared with constructing a complex multi-degree-of-freedom loading platform, the device has simple structure, and the technical requirements of experimenters during implantation and loading implementation are relatively low, and the device is easy to popularize.

[0019] The parts not involved in the device are the same as or can be realized by the prior art, the device has simple structure and convenient operation. BRIEF DESCRIPTION OF DRAWINGS

[0020] Figure 1 The installation diagram of the device for intervertebral disc degeneration of rat tail vertebrae is provided Figure 1 (The two metal rings are parallel, and the four springs are parallel); Figure 2 The installation diagram of the device for intervertebral disc degeneration of rat tail vertebrae is provided Figure 2 (The two metal rings are parallel, and the four springs are inclined); Figure 3 The installation diagram of the device for intervertebral disc degeneration of rat tail vertebrae is provided Figure 3 (The two metal rings are inclined to each other, and the four springs are parallel).

[0021] In the figure: metal ring 1; hook 2; hook spring 3; bone cortical nail 4; nail head 5. DETAILED DESCRIPTION

[0022] The technical solutions in the embodiments of the present application will be described clearly and completely below with reference to the drawings in the embodiments of the present application. Obviously, the described embodiments are only part of the embodiments of the present application, not all the embodiments.

[0023] Embodiment 1: A device for intervertebral disc degeneration of rat tail vertebrae, as shown in Figures 1 to 3As shown, including fixed units and loading units, loading units are set between two fixed units, the fixed unit includes two metal rings 1, respectively used to fix the adjacent vertebral bodies such as Co3, Co4 vertebral bodies of rat tail vertebrae on both sides of the target intervertebral disc above and below; The inner side of each metal ring 1 is provided with at least two, preferably three or four, nail members, which can penetrate the vertebral body cortical bone when implanted, thereby firmly anchoring the metal ring 1 on the vertebral body and ensuring that it will not loosen or shift during loading.

[0024] The metal ring 1 is made of a biocompatible material such as medical stainless steel or titanium alloy to reduce tissue rejection; The nail member includes a bone cortical nail 4 and a nail head 5, which are integrally formed between the bone cortical nail 4 and the nail head 5, and the inner wall of the metal ring 1 is provided with a plug hole matched with the bone cortical nail 4; The loading unit includes hooks 2 on the outer side of the two metal rings 1 and hook springs 3 connecting the hooks 2, a plurality of hooks 2 are arranged at equal angles on the outer side of each metal ring 1, as a preferred embodiment, 12 hooks 2 are arranged on each metal ring 1, and the central angle between adjacent hooks 2 is 30°, and such dense hook 2 layout provides a basis for fine adjustment of the mechanical loading direction; The loading element is a hook spring 3, by selecting hook springs 3 with different stiffness coefficients k, the size of the applied force can be controlled, and the two ends of the hook spring 3 are provided with hook or ring structure for convenient mounting on the hooks 2 of the two metal rings 1; The loading unit realizes the application of composite load by connecting the hooks 2 with adjustable relative positions and the hook springs 3, specifically: By connecting the hook springs 3 to the hooks 2 at specific positions on the two metal rings 1, the direction of the force line of action can be changed, and the moment applied to the intervertebral disc can be changed, by adjusting the relative angle between the connected hooks 2, for example, connecting the 0° position hook 2 of the upper metal ring 1 with the 30° position hook 2 of the lower metal ring 1, a torsional component can be actively introduced, by combining the use of different numbers, different connection angles and different stiffness of the hook springs 3, the proportion of axial force and torsional force can be accurately adjusted, and the mechanical environment under various motion states such as forward bending, backward stretching, left bending, right bending and various composite motions can be simulated, the pre-stretching or pre-compression amount of the hook spring 3 can also be used as a parameter to adjust the initial load size, and the connection mode of the hook spring 3 and the two fixed units can refer to the attached drawings Figures 1 to 3 .

[0025] Example 2: A device for rat tail vertebra intervertebral disc degeneration, its degeneration method, including the following steps: S1: Animal preparation and exposure: adult SD rats were selected, anesthetized by intraperitoneal injection of sodium pentobarbital or isoflurane inhalation, and after confirming that the rat's pain reflex was lost, the rat was fixed in a prone position on a constant temperature operating table, the tail was naturally stretched, and the animal's body temperature was maintained using an electric heating blanket; The hair on the dorsal surgical area of the tail was shaved, the skin was disinfected with iodophor and 75% alcohol alternately for 2-3 times, and a sterile drape was laid to expose the lumbar segment; S2: Metal ring 1 fixation: according to the diameter of the rat's lumbar vertebrae, select a size matching metal ring 1, put two metal rings 1 on the vertebral bodies of Co3 upper vertebra and Co4 lower vertebra, respectively, ensure that the ring body plane is parallel to the intervertebral disc plane, and the center of the ring is roughly aligned with the center of the intervertebral disc; Using a special tool or micro electric drill, a shallow hole is pre-drilled on the vertebral bone through the nail hole on the metal ring 1 to prevent splitting, and four bone cortical nails 4 on each metal ring 1 are recommended to be distributed symmetrically at an angle of 90 degrees vertically implanted into the vertebral body; Tighten the bone cortical nails 4 step by step to make the metal ring 1 closely fit the vertebral bone surface, and ensure that there is no looseness or rotation; S3: Mechanical loading scheme design: prepare four lightweight compression hook springs 3 with the same stiffness coefficient k, determine the stiffness of the hook spring 3, the position of the hook 2 to be connected, i.e. the angle, and the number of hook spring 3 connections according to the mechanical conditions simulated by the experiment; Design to connect the hooks 2 of the same phase of the upper and lower metal rings 1, for example, plan to connect the hooks 2 of 0°, 90°, 180°, 270° of the upper ring with the hooks 2 of 0°, 90°, 180°, 270° of the lower ring corresponding; According to the target compression force F and the stiffness coefficient k of the spring, calculate and preset the stretching amount Δx of the spring, because F=k*Δx, determine to use four springs 3 to provide symmetrical and stable load; S4: Loading implementation: according to the designed scheme, apply pure axial compression, connect four hook springs 3 to the hooks 2 of the same phase of the upper and lower metal rings 1, for example, the hooks 2 of 0°, 90°, 180°, 270° of the upper ring are respectively connected to the hooks 2 of 0°, 90°, 180°, 270° of the lower ring, at this time the hook spring 3 mainly generates compression force along the central axis of the vertebral body, and the torsional moment is offset, after installation is completed, the device starts to apply continuous mechanical stimulation to the intervertebral disc; At the moment when the spring 3 is installed, the device starts to apply the designed, continuous static or dynamic mechanical stimulation to the Co3-Co4 intervertebral disc; S5: Postoperative management and observation: after checking for active bleeding, use absorbable sutures to layer suture the muscle fascia and subcutaneous tissue, and use non-absorbable sutures or skin staplers to close the skin, and disinfect the wound again; The animals are placed in clean, warm individual cages for observation until fully conscious, subcutaneous injection of antibiotics such as penicillin for several days after operation to prevent infection, and analgesics such as ibuprofen sustained-release solution to relieve pain, free water and diet; The rats are routinely fed for 8 weeks, and their mental state, activity and wound healing state are observed daily. After 8 weeks, the animals are sacrificed by excessive anesthesia or carbon dioxide asphyxiation, and the caudal vertebrae segment containing the metal ring device, Co3, Co4 vertebrae and intervertebral disc is completely taken out; Micro-CT scanning is performed to evaluate the intervertebral disc height index and osteophyte formation; MRI T2 weighted image scanning is performed to evaluate the signal intensity and water content of the nucleus pulposus; After fixation, decalcification, embedding and sectioning, H&E staining and safranin O-fast green staining are performed, and the morphological changes of the tissue are observed under a microscope and graded according to the degeneration grade; the changes in the content of proteoglycans and type II collagen in the nucleus pulposus and annulus fibrosus can be further detected; Conclusion: Micro-CT scanning shows that the intervertebral space height of the loaded segment is significantly lower than that of the control group; Histological staining such as hematoxylin-eosin staining and safranin O-fast green staining can show typical degenerative manifestations such as a decrease in the number of nucleus pulposus cells and a decrease in the content of proteoglycans in the matrix.

[0026] Example 3: A device for intervertebral disc degeneration in rat caudal vertebrae, the difference between this embodiment and example 2 is that in the loading implementation step of S4, in order to simulate an asymmetric composite load, for example, to simulate the mechanical state under improper posture, an asymmetric connection method is used, two hook springs 3 with relatively large stiffness are connected to the hook 2 of the upper ring at 0° and the hook 2 of the lower ring at 30°, and the hook 2 of the upper ring at 180° and the hook 2 of the lower ring at 210°, while the other two hook springs 3 with slightly smaller stiffness are connected to the upper ring at 90° and the lower ring at 90°, and the upper ring at 270° and the lower ring at 270°, this connection method provides axial compression at the same time, due to the force line deviation, a continuous torsional moment is generated on the intervertebral disc; Conclusion: After 6 weeks of feeding, MRI T2 weighted image shows that the signal intensity of the intervertebral disc of the loaded segment decreases; Histological examination can observe that the annulus fibrosus appears to be layered and disordered or even torn, the intervertebral disc height is low, and the cartilage endplate is degenerated, and the degree of degeneration is more significant than that of the simple axial compression group.

[0027] The above is only the preferred specific implementation of the present application, but the protection scope of the present application is not limited to this, any skilled person in the art can make equivalent replacement or change according to the technical solution and the inventive concept of the present application within the technical range disclosed by the present application, which should be covered within the protection scope of the present application.

Claims

1. An apparatus for rat tail intervertebral disc degeneration, characterized in that, The application relates to a vertebral disc loading device, comprising: two fixing units for fixing adjacent vertebral bodies on the upper and lower sides of a target intervertebral disc; a loading unit arranged between the two fixing units; the loading unit comprises a plurality of hooks (2) arranged on the outer circumferences of metal rings (1) and hook springs (3) connected between the hooks (2), the two ends of the hook springs (3) being connected to the hooks (2) at different positions on the two metal rings (1), so as to exert adjustable compound loads on the intervertebral disc.

2. The device for rat tail intervertebral disc degeneration according to claim 1, wherein, Each fixing unit comprises a metal ring (1) and at least two nail pieces, the nail pieces being arranged on the inner circumferences of the metal rings (1) and being capable of penetrating the vertebral bone cortex to anchor the metal rings (1) on the vertebral bodies during implantation.

3. The device for rat tail intervertebral disc degeneration according to claim 2, wherein, The nail pieces comprise bone cortex nails (4) and nail heads (5), the bone cortex nails (4) and the nail heads (5) being integrally formed, and the inner wall of the circumference of the metal ring (1) is provided with a plug hole matched with the bone cortex nail (4).

4. The device for rat tail intervertebral disc degeneration according to claim 3, characterized in that, A plurality of groups of hooks (2) are arranged on each metal ring (1) and are distributed at equal intervals along the circumference.

5. The device for rat tail intervertebral disc degeneration according to claim 1, wherein, The two ends of the hook spring (3) are provided with hook-shaped or ring-shaped structures for being hung on the hooks (2).

6. The device for intervertebral disc degeneration of tail vertebrae of rats according to claim 5, characterized in that, The hook spring (3) can select a rigidity coefficient k, and the size of the exerted force is controlled by replacing hook springs (3) with different rigidity coefficients.

7. The device for intervertebral disc degeneration of rat tail vertebrae according to claim 6, characterized in that, The hook spring (3) can simulate single or compound mechanical environments in forward flexion, backward extension, lateral flexion or rotation motion states through different connection combinations.

8. The device for intervertebral disc degeneration of tail vertebrae of rats according to claim 7, characterized in that, A plurality of hook springs (3) are used in combination, and the proportion and direction of axial force, lateral force and torsional force exerted on the intervertebral disc are adjusted by connecting the hook springs (3) between the hooks (2) at different circumferential positions on the two metal rings (1).

9. The device for intervertebral disc degeneration of rat tail vertebrae according to claim 8, characterized in that, The two ends of the hook spring (3) are hung on the hooks (2) at different circumferential positions on the two metal rings (1) to change the direction of the action line of the load, and compound loads containing torsional components are exerted on the intervertebral disc.

10. The device for intervertebral disc degeneration of tail vertebrae of rats according to claim 1, characterized in that, The metal ring (1) is made of medical stainless steel or titanium alloy material.

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