Device and method for constructing mouse temporomandibular joint osteoarthritis animal model

Abstract

The invention discloses a device and method for constructing a mouse temporomandibular joint osteoarthritis animal model, and belongs to the technical field of animal experiment model construction.The device comprises an upper jaw tooth socket used for being worn on mouse upper jaw teeth and a lower jaw tooth socket used for being worn on mouse lower jaw teeth. The occlusal surface of the lower jaw tooth socket is provided with a plane guide plate inclining towards the outside of the oral cavity of the mouse, and the plane guide plate is used for interfering with the upper jaw tooth socket when being worn and guiding the lower jaw bone to deviate, so that unilateral anterior teeth are reversely combined to induce temporomandibular joint osteoarthritis. An active mechanical guide mechanism is created through the cooperation of the upper jaw tooth socket and the lower jaw tooth socket, especially the plane guide plate which is specially designed on the lower jaw tooth socket and inclines outwards. The structure directly and reliably creates a key biomechanical environment required for inducing TMJOA, and solves the fundamental problems of unstable interference force and inconsistent models caused by inaccurate shape of a manual tooth socket.

Description

Technical Field

[0001] This invention relates to the field of animal experimental model construction technology, and in particular to an apparatus and method for constructing a mouse temporomandibular joint osteoarthritis animal model. Background Technology

[0002] Temporomandibular joint osteoarthritis (TMJOA) is a common temporomandibular joint disease. Establishing a reliable animal model is fundamental for studying its pathogenesis and conducting drug intervention experiments. Mice are ideal experimental animals due to their clear genetic background and relatively low cost. Currently, the unilateral anterior crossbite modeling method is commonly used to construct mouse TMJOA models, which induces abnormal joint loading by altering the occlusal relationship of the teeth.

[0003] However, existing technologies are mainly focused on rat models, and face significant challenges when applied to mice. Because mouse teeth are extremely small, typically only millimeters in size, existing modeling methods used in rats are difficult to directly apply. Specifically, traditional manual bending of dental braces (e.g., using injection needles) is extremely difficult and inaccurate, leading to poor fit between the brace and teeth and difficulty in establishing a stable and consistent abnormal occlusal relationship. Inaccurate occlusal interference not only results in low model success rates but also significant individual-to-individual variability (high model heterogeneity), severely impacting the reliability and reproducibility of experimental data. Therefore, there is an urgent need for a device and method capable of achieving precise, stable, and reproducible unilateral anterior crossbite relationships within the mouse oral cavity. Summary of the Invention

[0004] The purpose of this invention is to overcome the shortcomings of the prior art and provide an apparatus and method for accurately, stably and reproducibly constructing a mouse model of temporomandibular joint osteoarthritis.

[0005] To achieve the above objectives, the present invention provides the following solution: This invention provides an apparatus for constructing a mouse model of temporomandibular joint osteoarthritis, comprising an maxillary dental brace for wearing on the upper teeth of a mouse and a mandibular dental brace for wearing on the lower teeth of a mouse. The occlusal surface of the mandibular dental brace is provided with a planar guide plate inclined towards the outside of the mouse's oral cavity, which is used to interfere with the maxillary dental brace during wearing, guiding the mandible to shift, thereby forming a unilateral anterior crossbite to induce temporomandibular joint osteoarthritis.

[0006] As one embodiment, both the maxillary brace and the mandibular brace are integrally formed from metal material using 3D printing technology.

[0007] As one implementation, the inner surface shape of the maxillary and mandibular dental braces matches the three-dimensional shape of the corresponding mouse tooth crown surface to achieve a close fit.

[0008] As one embodiment, the metal material is aerospace-grade stainless steel powder with a particle size range of 15-53 μm.

[0009] This invention also provides a method for constructing a mouse model of temporomandibular joint osteoarthritis, comprising the following steps: S1. Acquisition of 3D Tooth Data: Acquire high-precision 3D data of the maxillary and mandibular teeth of mice; S2. Digital design of braces: Based on the three-dimensional data, design three-dimensional models of the maxillary braces and the mandibular braces respectively, and design the planar guide plate on the occlusal surface of the mandibular braces; S3. Braces manufacturing: Based on the designed three-dimensional model, the maxillary braces and the mandibular braces are manufactured using metal three-dimensional printing technology; S4. Braces wearing and fixation: The manufactured maxillary braces and mandibular braces are worn and fixed on the corresponding mouse teeth respectively. The mice are guided by the planar guide plate to form unilateral anterior crossbite, thereby constructing a temporomandibular joint osteoarthritis model.

[0010] As one implementation method, in step S1, micro-CT scans are performed on isolated mouse maxilla and mandible samples. Projection data is obtained by rotating the samples 360°. After three-dimensional reconstruction and segmentation, STL format three-dimensional data containing the geometry of the crown surface is obtained. Furthermore, before and after scanning, standard parts of known dimensions were used to verify the equipment's dimensional accuracy, and the same sample was repeatedly scanned and processed to assess data repeatability error.

[0011] As one implementation method, in step S2, during digital design, the inner surface of the brace is offset to form a fitting gap with the crown, and the slope angle and occlusal elevation of the planar guide are parametrically designed to produce the expected mandibular offset.

[0012] As one implementation, in step S3, the metal 3D printing technology is selective laser melting technology, the printing equipment used is an EOSINT M280 metal 3D printer, and the printing material is 316L stainless steel powder or 17-4PH stainless steel powder.

[0013] As one implementation method, in step S4, the maxillary dental brace and the mandibular dental brace are respectively bonded and fixed to the corresponding tooth surfaces of the mouse using light-cured resin.

[0014] The present invention achieves the following technical effects compared to the prior art: The device disclosed in this invention for constructing a mouse model of temporomandibular joint osteoarthritis (TMJOA) utilizes the coordination of upper and lower jaw braces, particularly a specially designed outward-tilting planar guide plate on the lower jaw brace, to create an active mechanical guidance mechanism. When the mouse closes its mouth, the planar guide plate interferes with the upper jaw brace, forcibly guiding the mandible to produce a small but definite offset in a predetermined direction (such as the left or right side), causing the offset lateral incisors to form a stable reverse overbite contact relationship (unilateral anterior crossbite). This structure directly constructs the key biomechanical environment required for inducing TMJOA through geometric constraints, thereby significantly reducing interference force fluctuations caused by deviations in the shape of the hand-made braces and improving the consistency and reproducibility of the model. Attached Figure Description

[0015] To more clearly illustrate the technical solutions in the embodiments of the present invention or the prior art, the drawings used in the embodiments will be briefly introduced below. Obviously, the drawings described below are only some embodiments of the present invention. For those skilled in the art, other drawings can be obtained based on these drawings without creative effort.

[0016] Figure 1 This is a mesial view of the maxillary braces in an embodiment of the present invention; Figure 2 This is a schematic diagram of the occlusal plane of the maxillary brace in an embodiment of the present invention; Figure 3 This is a schematic diagram of the distal view of the maxillary brace in an embodiment of the present invention; Figure 4 This is a mesial view of the mandibular brace in an embodiment of the present invention; Figure 5 This is a schematic diagram of the occlusal plane of the mandibular brace in an embodiment of the present invention; Figure 6 This is a schematic diagram of the distal view of the mandibular brace in an embodiment of the present invention; Among them, 1. Maxillary brace; 11. Overflow hole; 2. Mandibular brace; 21. Planar guide plate. Detailed Implementation

[0017] The technical solutions of the embodiments of the present invention will be clearly and completely described below with reference to the accompanying drawings. Obviously, the described embodiments are only some embodiments of the present invention, and not all embodiments. Based on the embodiments of the present invention, all other embodiments obtained by those skilled in the art without creative effort are within the scope of protection of the present invention.

[0018] The purpose of this invention is to overcome the shortcomings of the prior art and provide an apparatus and method for accurately, stably and reproducibly constructing a mouse model of temporomandibular joint osteoarthritis.

[0019] To make the above-mentioned objects, features and advantages of the present invention more apparent and understandable, the present invention will be further described in detail below with reference to the accompanying drawings and specific embodiments.

[0020] like Figures 1-6 As shown, this embodiment provides an apparatus for constructing a mouse model of temporomandibular joint osteoarthritis, including a maxillary dental sleeve 1 for wearing on the upper teeth of the mouse and a mandibular dental sleeve 2 for wearing on the lower teeth of the mouse. The occlusal surface of the mandibular dental sleeve 2 is provided with a planar guide plate 21 that is inclined outwards from the mouse's oral cavity. This guide plate is designed to interfere with the maxillary dental sleeve 1 during wear, guiding the mandible to shift and thus forming a unilateral anterior crossbite to induce temporomandibular joint osteoarthritis. This embodiment creates an active mechanical guidance mechanism through the cooperation of the maxillary and mandibular dental sleeves, especially the specially designed outwardly inclined planar guide plate 21 on the mandibular dental sleeve 2. When the mouse closes its mouth, the planar guide plate 21 interferes with the maxillary dental brace 1, forcibly guiding the mandible to produce a slight but definite offset in a predetermined direction (such as the left or right side), so that the offset lateral incisors form a stable reverse overlay contact relationship (unilateral anterior crossbite). This structure directly constructs the key biomechanical environment required to induce TMJOA in a geometrically constrained manner, thereby significantly reducing the fluctuation of interference force caused by the shape deviation of the manual dental brace and improving the consistency and repeatability of the model. Moreover, the device structure of wearing dental braces on both the upper and lower jaws in this embodiment is based on in-depth consideration of the biomechanics of long-term occlusal interference. Under physiological conditions, the upper and lower jaw teeth of mice will undergo uniform and slow physiological wear through normal chewing activities. If the intervention dental brace is only worn on a single jaw (the lower jaw), the dental brace will protect the mandibular teeth it covers, so that their wear almost stops; while the corresponding maxillary teeth, because they lose their normal occlusal contact object (i.e., the unprotected mandibular teeth), will have direct and continuous mechanical contact and friction with the abnormally hard surface of the mandibular dental brace 2, resulting in non-physiological excessive wear or even fracture. This asymmetric wear caused by single-jaw protection alters the actual occlusal height and contact relationship over time, causing uncontrollable drift of the initially designed occlusal interferences (such as the angle and height of the underbite incline), ultimately disrupting the long-term stability and consistency of the model's occlusal state. Therefore, this device, by setting up the maxillary brace 1, aims to provide a stable, wear-resistant, and shape-consistent interaction surface for the planar guide plate of the mandibular brace 2, thereby maintaining the occlusal interference relationship in the initially designed expected state over a long experimental period, ensuring the reliability and repeatability of the disease induction process.

[0021] Optionally, the tilt direction of the planar guide plate 21 can be set to guide the mandible to shift to the left (forming a right-sided crossbite) or to the right (forming a left-sided crossbite), depending on the experimental design requirements. The planar guide plate 21 can be located at the center of the front end of the mandibular brace 2 and tilted to one side, or it can be directly integrated into the left or right side of the mandibular brace 2.

[0022] As one implementation method, both the maxillary brace 1 and the mandibular brace 2 are integrally formed from metal material using 3D printing technology. Using 3D printing to integrally form the braces avoids problems such as irregular shapes and fragile connection points that arise from traditional hand-bending. The metal material ensures sufficient strength and durability of the device, maintaining structural integrity during the mouse's long-term chewing activities and continuously providing stable occlusal interference.

[0023] Alternatively, in addition to stainless steel, medical metals with better biocompatibility, such as titanium alloys and cobalt-chromium alloys, can also be selected as metal materials.

[0024] Alternatively, the 3D printing technology can be selective laser melting (SLM), electron beam melting (EBM), or direct metal laser sintering (DMLS).

[0025] As one implementation, the inner surface shapes of the maxillary dental brace 1 and the mandibular dental brace 2 are matched with the three-dimensional shapes of the corresponding mouse tooth crowns to achieve a tight fit. The matching of the inner surface of the brace with the individual mouse tooth crown shape ensures that the brace can be securely worn on the teeth and is not easily loosened by chewing or licking. This tight fit is the physical basis for transmitting precise and stable occlusal interference forces, avoiding changes in interference forces caused by brace movement or displacement, and improving the reliability of the model.

[0026] As one implementation method, the metal material is aerospace-grade stainless steel powder with a particle size ranging from 15 micrometers to 53 micrometers. Using aerospace-grade metal powder with uniform and fine particle size can significantly improve the forming accuracy, surface finish, and internal density of 3D printed parts. This is particularly important for printing small, intricately structured parts such as mouse dental braces, ensuring the dimensional accuracy and edge sharpness of key features such as the planar guide plate 21, thereby guaranteeing the precise realization of its guiding function.

[0027] Optionally, the stainless steel powder is 316L stainless steel powder. The particle size distribution D50 (median particle size) is preferably between 20 micrometers and 40 micrometers to balance flowability and printing resolution.

[0028] Optionally, the stainless steel powder is 17-4PH stainless steel powder.

[0029] This invention also provides a method for constructing a mouse model of temporomandibular joint osteoarthritis, comprising the following steps: S1. Acquisition of 3D Tooth Data: Acquire high-precision 3D data of the maxillary and mandibular teeth of mice; S2. Digital design of braces: Based on three-dimensional data, three-dimensional models of maxillary braces 1 and mandibular braces 2 are designed respectively, and a planar guide plate 21 is designed on the occlusal surface of mandibular braces 2; S3. Braces Manufacturing: Based on the three-dimensional model of the design, the upper jaw braces 1 and the lower jaw braces 2 were manufactured using metal 3D printing technology; S4. Fitting and Fixation of Braces: The manufactured maxillary braces 1 and mandibular braces 2 are fitted and fixed to the corresponding mouse teeth respectively. The mice are guided by the planar guide plate 21 to form unilateral anterior crossbite, thereby constructing a temporomandibular joint osteoarthritis model.

[0030] This embodiment provides a complete, digital model construction process for constructing a mouse temporomandibular joint osteoarthritis animal model. From individualized data collection to targeted structural design, and then to high-precision additive manufacturing and clinical fixation, each step is designed to ensure that the final occlusal interference (unilateral anterior crossbite) in mice strictly conforms to the design expectations, is highly controllable and reproducible, thereby achieving the standardized construction of the TMJOA animal model.

[0031] As one implementation method, the specific steps for acquiring 3D tooth data are as follows: The maxilla and mandible (including teeth) obtained from euthanized mice are used as ex vivo samples for 3D scanning. Before scanning, soft tissues such as skin are removed, but the gingiva is preserved, and the tissue is fixed in a stable state to avoid geometric distortion caused by micro-movements during the scanning process. Simultaneously, the sample is placed in the center of the scanning field of view, and the minimum necessary scanning field of view covering the crown, root, and alveolar bone is selected to obtain higher voxel resolution. During scanning, projection data is acquired by rotating the sample 360° with the turntable, and artifacts are reduced through high-overlap angle sampling and stable exposure conditions. For cases where occlusion or high-density structures cause local information loss, the sample can be re-scanned after changing its orientation in a fixed fixture. Subsequently, the data from different orientations are registered and fused in the reconstruction software to achieve comprehensive coverage of the tooth geometry. In the reconstruction stage, uniform reconstruction parameters (such as filtering / iterative reconstruction strategies) are used to obtain volumetric data, and consistent threshold / region growth and necessary manual corrections are used in the segmentation stage to extract the tooth and jawbone surfaces. Finally, STL format 3D data is exported for subsequent CAD design.

[0032] Optionally, the scanner model is OptimScan 5M Plus, the camera resolution is 5 megapixels, and the software is OptimScan.

[0033] As one implementation method, in step S1, micro-CT scans are performed on isolated mouse maxilla and mandible samples. Projection data is acquired by rotating the samples 360°, and after 3D reconstruction and segmentation, STL format 3D data containing the geometry of the tooth crown surface is obtained. Furthermore, before and after scanning, standard parts of known dimensions are used for equipment dimensional verification, and the same sample is repeatedly scanned and processed to assess data repeatability errors. Using micro-CT to scan isolated samples can obtain sub-micron resolution 3D data of the tooth surface with rich detail. Rigorous dimensional verification and repeatability evaluation ensure the absolute dimensional accuracy and data stability of the digital model, which is the foundation for all subsequent personalized design and high-precision manufacturing, fundamentally eliminating the problem of mismatched braces caused by data errors.

[0034] Optionally, the mesh can be minimized and smoothed / patched before exporting the STL format 3D data, and relevant parameters can be recorded to avoid systematic dimensional deviations introduced by excessive mesh processing.

[0035] Optionally, the scanning resolution of the micro-CT can be set to 5-10 micrometers as needed. Segmentation can be performed using thresholding combined with manual trimming to ensure accurate extraction of the crown contour. Standard components can be tungsten or ceramic spheres of known diameter.

[0036] As one implementation method, in step S2, during digital design, the main body of the dental crown is generated by offsetting and thickening the crown veneer surface. The inner surface of the dental crown is offset to form a fitting gap with the crown, and the edges are optimized through trimming, rounding, or chamfering. The bevel angle and occlusal elevation of the planar guide plate 21 are parametrically designed to produce the expected mandibular offset. The tiny gap formed by the inner surface offset provides space for the adhesive, ensuring that the dental crown is firmly fixed without compressing the tooth. Parametric design of the key parameters of the planar guide plate 21 allows researchers to quantify and control the intensity of occlusal interference (such as the magnitude of the offset), thereby establishing TMJOA models of different severity levels to meet diverse research needs and enhance the scientific rigor and flexibility of the method. It is understood that the bevel angle of the planar guide plate 21 refers to the acute angle formed between the inclined surface of the planar guide plate 21 and the horizontal reference plane.

[0037] Optionally, the fit gap is typically 50-150 micrometers. The bevel angle can be set between 30 and 70 degrees according to biomechanical goals. The occlusal elevation (i.e., the height of the planar guide plate 21) can be calculated and set according to the required mandibular offset.

[0038] As one implementation method, the specific steps of digital design for dental braces are as follows: STL format 3D data of the extracted maxillary teeth / jawbone from mice is imported into Geomagic Studio 2016 for denoising, smoothing, cavity filling, mesh simplification, and surface reconstruction to obtain a continuously editable tooth surface model. Subsequently, it is imported into UG (Siemens NX) 10.0 to establish a unified coordinate system and reference (occlusal plane / tooth long axis direction, etc.). The main body of the dental brace is generated by offsetting and thickening the crown occlusal surface, and the edges are optimized through trimming, rounding / chamfering, etc. For unilateral anterior crossbite intervention, a unilateral intervention structure (crossbite ramp / enhanced contact surface) is constructed on the occlusal surface of the dental brace. Key parameters include ramp direction, ramp angle, occlusal elevation, and the area and position of the contact area. These parameters are set according to the intervention side and the expected occlusal guidance direction, and are iteratively adjusted through virtual occlusal contact checks and assembly interference checks. Finally, STL and STEP / IGES format 3D data are exported for manufacturing and experimental implementation.

[0039] As one implementation method, in step S3, the metal 3D printing technology used is selective laser melting (SLM), and the printing equipment is an EOSINT M280 metal 3D printer. The printing material is 316L stainless steel powder or 17-4PH stainless steel powder. SLM is particularly suitable for manufacturing dense metal parts with complex geometries and internal structures. Using industrial-grade equipment like the EOSINT M280 in conjunction with a mature stainless steel powder material system ensures a stable process and reliably achieves high-precision, high-strength manufacturing of mouse dental braces, guaranteeing the consistency of part quality during mass production.

[0040] Optionally, the printing layer thickness can be set to 20-40 micrometers to improve detail.

[0041] Optionally, standard post-processing can be performed after printing, including removal of support structures, sandblasting, cleaning, and sterilization.

[0042] Optionally, after printing, size verification and fit adjustment are performed. Size verification is done by directly attaching the dental brace to the mouse's teeth. If the fit is not good enough, the digital design of the dental brace in step S2 is repeated.

[0043] In one implementation method, in step S4, the maxillary dental brace 1 and the mandibular dental brace 2 are respectively bonded and fixed to the corresponding tooth surfaces of the mouse using light-cured resin. Light-cured resin is simple and quick to use, and the curing time is controllable. Its excellent flow properties fully fill the tiny gaps between the dental brace and the teeth, and after curing, it forms a strong mechanical interlocking force and chemical adhesive force, ensuring that the dental brace remains stable and does not fall off during long-term experimental periods, thereby guaranteeing the continuity of occlusal interference.

[0044] Optionally, since less light-cured resin is required for bonding the maxillary brace 1, excessive light-cured resin residue may affect the retention of the maxillary brace 1. Therefore, the maxillary brace 1 is provided with an overflow hole 11 for overflowing light-cured resin.

[0045] Optionally, the light-cured resin is a dental flowable resin. Before bonding, the tooth surface can be lightly sandblasted or acid-etched, and a dental adhesive can be applied to further enhance bond strength.

[0046] Specific examples have been used to illustrate the principles and implementation methods of this invention. The descriptions of the above embodiments are only for the purpose of helping to understand the method and core ideas of this invention. Furthermore, those skilled in the art will recognize that, based on the ideas of this invention, there will be changes in the specific implementation methods and application scope. Therefore, the content of this specification should not be construed as a limitation of this invention.

Claims

1. A device for constructing a mouse model of temporomandibular joint osteoarthritis, characterized in that, The invention includes an maxillary dental brace (1) for wearing on the upper teeth of a mouse and a mandibular dental brace (2) for wearing on the lower teeth of a mouse. The occlusal surface of the mandibular dental brace (2) is provided with a planar guide plate (21) that is inclined toward the outside of the mouse's oral cavity. This guide plate is used to interfere with the maxillary dental brace (1) when worn, thereby guiding the mandible to shift and forming a unilateral anterior crossbite to induce temporomandibular joint osteoarthritis.

2. The apparatus for constructing a mouse model of temporomandibular joint osteoarthritis according to claim 1, characterized in that, Both the maxillary brace (1) and the mandibular brace (2) are integrally formed from metal materials using three-dimensional printing technology.

3. The apparatus for constructing a mouse model of temporomandibular joint osteoarthritis according to claim 1, characterized in that, The inner surface shapes of the maxillary brace (1) and the mandibular brace (2) are matched with the three-dimensional shapes of the corresponding mouse tooth crown surfaces to achieve a close fit.

4. The apparatus for constructing a mouse model of temporomandibular joint osteoarthritis according to claim 2, characterized in that, The metal material is aerospace-grade stainless steel powder with a particle size range of 15-53 μm.

5. A method for constructing a mouse model of temporomandibular joint osteoarthritis, characterized in that, The apparatus for constructing a mouse model of temporomandibular joint osteoarthritis according to any one of claims 1-4, comprising the following steps: S1. Acquisition of 3D Tooth Data: Acquire high-precision 3D data of the maxillary and mandibular teeth of mice; S2. Digital design of braces: Based on the three-dimensional data, three-dimensional models of the maxillary braces (1) and the mandibular braces (2) are designed respectively, and the planar guide plate (21) is designed on the occlusal surface of the mandibular braces (2). S3. Braces manufacturing: Based on the designed three-dimensional model, the maxillary braces (1) and the mandibular braces (2) are manufactured using metal three-dimensional printing technology. S4. Wearing and fixing of dental braces: The manufactured maxillary dental brace (1) and mandibular dental brace (2) are worn and fixed on the corresponding mouse teeth respectively. The mouse forms a unilateral anterior crossbite through the guiding action of the planar guide plate (21), thereby constructing a temporomandibular joint osteoarthritis model.

6. The method for constructing a mouse model of temporomandibular joint osteoarthritis according to claim 5, characterized in that, In step S1, micro-CT scans are performed on isolated mouse maxilla and mandible samples. Projection data is obtained by rotating the samples 360°. After three-dimensional reconstruction and segmentation, STL format three-dimensional data containing the geometry of the crown surface is obtained. Furthermore, before and after scanning, standard parts of known dimensions were used to verify the equipment's dimensional accuracy, and the same sample was repeatedly scanned and processed to assess data repeatability error.

7. The method for constructing a mouse model of temporomandibular joint osteoarthritis according to claim 5, characterized in that, In step S2, during digital design, the inner surface of the brace is offset to form a fitting gap with the crown, and the slope angle and occlusal elevation of the planar guide plate (21) are parametrically designed so that it can produce the expected mandibular offset.

8. The method for constructing a mouse model of temporomandibular joint osteoarthritis according to claim 5, characterized in that, In step S3, the metal 3D printing technology is selective laser melting technology, the printing equipment used is EOSINT M280 metal 3D printer, and the printing material is 316L stainless steel powder or 17-4PH stainless steel powder.

9. The method for constructing a mouse model of temporomandibular joint osteoarthritis according to claim 5, characterized in that, In step S4, the maxillary dental crown (1) and the mandibular dental crown (2) are bonded and fixed to the corresponding tooth surfaces of the mouse using light-cured resin.

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