Small animal allogeneic bone cartilage transplantation instrument

Abstract

The invention provides a small animal allogeneic bone cartilage transplantation instrument. The small animal allogeneic bone cartilage transplantation instrument is characterized by comprising a small animal defect model making device and an allogeneic bone cartilage graft extracting and implanting device which are matched for use, wherein the small animal defect model making device comprises a sharp-bottomed manual bone grinding drill and a flat-bottomed manual bone grinding drill; the sharp-bottomed manual bone grinding drill is used for preliminarily making a small animal defect model; the flat-bottom manual bone grinding drill is used for leveling and shaping the small animal defect model; the allogeneic bone cartilage graft extracting and implanting device comprises a multifunctional transplanter and a multifunctional measurer, the multifunctional transplanter is used for extracting an allogeneic bone cartilage graft; and the multifunctional measurer measures the depth of the small animal defect model and pushes the allogeneic bone cartilage graft extracted from the multifunctional transplanter into the small animal defect model. The device can be used for simply and quickly manufacturing the small animal bone cartilage transplantation model with high quality.

Description

Technical Field

[0001] The invention relates to the field of small animal allogeneic osteochondrocyte transplantation, and in particular to a small animal allogeneic osteochondrocyte transplantation device. Background Art

[0002] Articular cartilage defect is a common disease that causes pain, swelling, dysfunction, and accelerates joint degeneration. Since cartilage lacks nerves and blood vessels, it cannot repair itself once damaged, so the treatment of young and middle-aged patients with cartilage defects is particularly difficult in clinical practice. Osteochondral allograft (OCA) has a wide clinical history of repairing osteochondral defects. The United States, Canada and other European and American countries have conducted a large number of clinical studies on OCA treatment of cartilage damage, and the 10-year survival rate of the graft exceeds 75%. OCA is different from other surgical methods. It is a method from clinical research to basic research. Although OCA has been carried out in the United States for more than 40 years to repair articular cartilage, most of the research is clinical research, basic research is relatively small, and there is a lack of research on mechanisms. This may be related to the choice of experimental animals. At present, most of the osteochondral transplantation models in research exist in large animals, such as pigs, dogs, sheep, horses, etc. These animals are widely used in osteochondral transplantation research because they have a large knee joint surface and are easy to model. However, these large animals are difficult to modify at the genetic level (because there are few transgenic large animals, there is a serious lack of research prototypes, which is not conducive to the development of research), which has affected researchers' in-depth research on the mechanism of OCA repairing articular cartilage, and basic research has been hindered.

[0003] Small animals, such as mice, are significantly superior to large animals because of the large number of transgenic mice, which can be used for in-depth mechanism research. They are also easy to raise and breed, low cost, easy to obtain and cheap experimental reagents, and fewer ethical issues. However, mice have received little attention from researchers because of their small knee joints, thin and easily damaged articular cartilage, and fragile subchondral bone, which make OCA modeling extremely difficult.

[0004] Moreover, there is currently no dedicated small animal (rats, mice) osteochondral transplantation instrument. Therefore, in some studies, when a small animal defect model must be carried out, an electric drill is often used, and power grinding can easily lead to cartilage defects. In addition, the twist drill equipped with the electric drill has a pointed bottom, and the transplanted bone bed produced is strictly a combination of cylindrical and conical shapes, which is not conducive to the filling of cylindrical transplants and the postoperative recovery of animal recipients. Moreover, the heat generated during power grinding will also destroy the integrity of the research object. In other words, the target scientific research purpose cannot be achieved.

[0005] In addition, the same dilemma arises in that there is currently no instrument specifically designed for small animal osteochondral transplantation, and cylindrical grafts can only be obtained using instruments from other disciplines, such as skin trephine and ophthalmic trephine. Such instruments are prone to damage the surface of the transplanted cartilage during the process of extracting small animal osteochondral grafts, and because the subchondral bone of mice is extremely fragile, it is easy to be crushed by tweezers, making it difficult to trim and remove, and thus it is impossible to adjust and match the thickness of the graft (such as Figure 1 shown). Summary of the invention

[0006] The present invention aims to overcome the above-mentioned defects and proposes a simple, rapid and efficient small animal osteochondral transplantation modeling device and its operation method, aiming to accelerate the basic research progress of allogeneic osteochondral transplantation, deepen our understanding of knowledge in this field, and further promote the innovation and development of allogeneic osteochondral transplantation technology.

[0007] The present invention provides a small animal allogeneic osteochondral transplantation device, which is aimed at extracting and implanting micro-osteochondral transplants of small animals, and is characterized by comprising a small animal defect model making device and an allogeneic osteochondral transplant extraction and implantation device for matching use;

[0008] The above-mentioned small animal defect model making device comprises a pointed-bottom manual bone grinding drill and a flat-bottom manual bone grinding drill;

[0009] The above-mentioned pointed-bottom manual bone grinding drill was used to make a preliminary defect model for small animals;

[0010] The above-mentioned flat-bottomed manual bone grinding drill is used to level and shape the defect model of small animals;

[0011] The above-mentioned allogeneic osteochondral graft extraction and implantation device comprises a multifunctional implanter and a multifunctional measuring device;

[0012] The above multifunctional transplanter is used to extract allogeneic osteochondral grafts;

[0013] The multifunctional measuring device measures the depth of the small animal defect model and pushes the allogeneic osteochondral graft extracted from the multifunctional transplanter into the small animal defect model.

[0014] Furthermore, the present invention provides a small animal allogeneic osteochondral transplantation device, which is also characterized by:

[0015] The above-mentioned pointed bottom manual bone grinding drill comprises a pointed bottom reamer and a handle;

[0016] The pointed bottom reamer is detachably connected to the handle in a mutually perpendicular manner;

[0017] The outer surface of the cutter head of the pointed bottom reamer is provided with scales.

[0018] Furthermore, the present invention provides a small animal allogeneic osteochondral transplantation device, which is also characterized by:

[0019] The above-mentioned flat-bottom manual bone grinding drill comprises a flat-bottom reamer and a handle;

[0020] The flat bottom reamer is detachably connected to the handle in a mutually perpendicular manner;

[0021] The outer surface of the cutter head of the flat bottom reamer is provided with scales.

[0022] Furthermore, the present invention provides a small animal allogeneic osteochondral transplantation device, which is also characterized by:

[0023] The outer diameter of the flat-bottom reamer is the same as the outer diameter of the pointed-bottom reamer of the pointed-bottom manual bone grinding drill.

[0024] Furthermore, the present invention provides a small animal allogeneic osteochondral transplantation device, which is also characterized by:

[0025] The above-mentioned multifunctional transplanter comprises a transplant extraction part and a handle;

[0026] The above-mentioned graft extraction piece is a hollow structure;

[0027] The graft extraction member is detachably connected to the handle in a mutually perpendicular manner;

[0028] The head of the transplant extractor is provided with scales on its outer surface.

[0029] Furthermore, the present invention provides a small animal allogeneic osteochondral transplantation device, which is also characterized by:

[0030] The graft extraction member has a graft thickness measuring portion in the middle thereof;

[0031] The graft thickness measuring part has a 0 reference line and scales.

[0032] Furthermore, the present invention provides a small animal allogeneic osteochondral transplantation device, which is also characterized by:

[0033] The above multifunctional measuring device comprises a measuring rod and a handle;

[0034] The measuring rod is detachably connected to the handle in a perpendicular manner;

[0035] The measuring rod has a scale on its outer surface at the head;

[0036] The outer diameter of the measuring rod is not greater than the inner diameter of the hollow structure of the transplant extraction member.

[0037] Furthermore, the present invention provides a small animal allogeneic osteochondral transplantation device, which is also characterized by:

[0038] The outer surface of the measuring rod also has a 0 reference line;

[0039] When the measuring rod is completely inserted from the handle end into the hollow structure of the graft extraction member, the 0 reference line coincides with the 0 reference line on the graft thickness measuring portion.

[0040] Furthermore, the present invention provides a small animal allogeneic osteochondral transplantation device, which is also characterized by:

[0041] The outer diameter of the flat-bottom reamer of the flat-bottom manual bone grinding drill is the same as the inner diameter of the hollow structure of the graft extraction piece.

[0042] A method for using a small animal allogeneic osteochondral transplantation device, characterized in that it comprises the following steps:

[0043] S1. Obtain small animal defect models using a pointed-bottom manual bone drill and a flat-bottom manual bone drill;

[0044] S2. Obtain the transplanted tissue through the multifunctional transplanter;

[0045] S3. Determine the thickness of the graft using a multifunctional measuring device and push it into the small animal defect model via a multifunctional transplanter.

[0046] Functions and effects of the present invention:

[0047] The present invention uses a small animal defect modeling device and an allogeneic osteochondral extraction and implantation device for matching use. The main function of the two manual bone grinding drills is to cooperate with each other to manually grind out a cylindrical transplant bone bed; the function of the multifunctional measuring device is to measure the depth of the transplant bone bed, the thickness of the graft, and to push out the osteochondral graft in the multifunctional transplanter; the multifunctional transplanter takes into account multiple uses such as graft acquisition, trimming, matching, and implantation. This set of instruments can be customized with instruments of appropriate sizes according to the size of mouse and rat joints and experimental needs, and can perform a series of operations such as osteochondral defect modeling, graft acquisition, trimming and implantation, so that the establishment of small animal osteochondral transplantation models is simplified and standardized, which is conducive to the development and improvement of allogeneic osteochondral transplantation. BRIEF DESCRIPTION OF THE DRAWINGS

[0048] Figure 1 .Practical photos and staining results of extracting osteochondral grafts from small animals using existing equipment.

[0049] Figure 2 .Schematic diagram of the structure of a pointed-bottom manual bone grinding drill;

[0050] Figure 3.Schematic diagram of the structure of a flat-bottomed manual bone grinding drill;

[0051] Figure 4 .Schematic diagram of the structure of the multifunctional measuring device;

[0052] Figure 5 .Schematic diagram of the structure of the multifunctional transplanter;

[0053] Figure 6 . Flowchart of graft bone bed modeling and graft placement;

[0054] Figure 7 .The posterior knee joint pulley area;

[0055] Figure 8 .Use a pointed hand-made bone drill to locate the articular cartilage in the pulley area of ​​the recipient knee joint;

[0056] Fig. 9 .A circular cartilage defect model was created using a hand-made bone drill with a pointed bottom;

[0057] Fig.10 . Use a flat-bottomed manual bone drill to grind the cartilage defect;

[0058] Fig.11 .Use a flat-bottomed hand-grinded bone drill to grind a cylindrical bone graft bed;

[0059] Fig.12 . Find the harvesting site corresponding to the recipient's transplant bone bed in the donor's knee joint pulley;

[0060] Fig.13 . Status after transplantation is completed;

[0061] Fig.14 .Micro-CT scan showed successful matching of the graft and the graft bone bed;

[0062] Fig.15 .Two-dimensional and three-dimensional images show that the graft completely fills the graft bone bed;

[0063] Fig.16 .A 1mm diameter osteochondral transplantation model was made at the trochlea of ​​the rat knee joint;

[0064] Fig.17 A 1mm diameter osteochondral transplantation model was created at the trochlea of ​​the mouse knee joint. DETAILED DESCRIPTION

[0065] This embodiment provides a small animal allogeneic osteochondral transplantation device, which is aimed at extracting and implanting micro-osteocartilage grafts of small animals, and includes a matching small animal defect model making device and an allogeneic osteochondral extraction and implantation device;

[0066] Among them, the small animal defect model making device includes a pointed bottom manual bone grinding drill (such as Figure 2 ) and flat-bottomed manual bone grinding drills (such as Figure 3 );

[0067] Allogeneic osteochondral extraction and implantation device, including a multifunctional implant (such as Figure 5 ) and multi-function measuring instruments (such as Figure 4 );

[0068] like Figure 2 As shown, the pointed bottom manual bone grinding drill comprises a pointed bottom reamer 101 and a handle 104;

[0069] The pointed bottom reamer 101 is detachably connected to the handle 104 via a detachable device 103 and is vertically connected to each other;

[0070] The detachable device 103 is an internal thread nut, which matches the external thread at the connection position between the pointed bottom reamer 101 and the handle 104. After the pointed bottom reamer 101 is inserted into the handle through the through hole in the middle of the handle 104, the nut is sleeved onto the outside of the reamer and screwed together to achieve a fixed connection between the two.

[0071] The pointed bottom reamer 101 has a scale 102 on its outer surface.

[0072] The function of the pointed-bottom manual bone grinding drill is to position and prevent slipping to form a defect with a cylindrical main body and a conical bottom on the cartilage.

[0073] like Figure 3 As shown, the flat-bottom manual bone grinding drill comprises a flat-bottom reamer 201 and a handle 204;

[0074] The flat bottom reamer 201 is detachably connected to the handle 204 in a perpendicular manner through a detachable device 203 (same as above);

[0075] The pointed bottom reamer 201 has a scale 202 on its outer surface.

[0076] The function of the flat-bottom manual bone grinding drill is to process the defect area created by the pointed-bottom manual bone grinding drill and finally form a cylindrical transplant bone bed with an appropriate depth.

[0077] like Figure 4 As shown, the multifunctional measuring device comprises a cylindrical measuring rod 301 and a handle 305;

[0078] The cylindrical measuring rod 301 is detachably connected to the handle 305 in a perpendicular manner through a detachable device 304 (same as above);

[0079] The outer surface of the blade of the cylindrical measuring rod 301 is provided with a scale 302 and a 0 scale mark line 303 corresponding to the multifunctional transplanter.

[0080] The multifunctional measuring device is used to measure the depth of the transplanted bone bed, to cooperate with the multifunctional transplanter to measure the thickness of the transplanted plant and to trim the transplanted plant.

[0081] like Figure 5 As shown, the multifunctional transplanter comprises a transplant extraction member 401 and a handle 405;

[0082] The graft extraction member 401 has a conical opening and is a hollow structure, which can accommodate the cylindrical measuring rod 301 to enter and exit, and the entry and exit ends are 406, which are connected to the detachable handle 405 through a detachable device 404 (same as above) in a mutually perpendicular manner;

[0083] The graft extraction part 401 has a scale 402 and a graft thickness measuring part 403 on its head outer surface. The graft thickness measuring part has a 0 reference line and scales. When the scale mark line 303 of the multifunctional measuring device is aligned with 0 on the graft thickness measuring part 403, the bottom of the multifunctional measuring device is flush with the bottom of the multifunctional transplanter (the distance from the scale mark line to the bottom of the multifunctional measuring device = the distance from the 0 scale to the graft acquisition cone mouth).

[0084] The multifunctional transplanter is used to obtain the transplant, measure the thickness of the transplant, trim the transplant, and match the shape of the transplant.

[0085] The procedure for small animal allogeneic osteochondral transplantation using the above kit is as follows: Figure 6 As shown:

[0086] The small animals used in the transplantation process of this experimental example were 10-week-old female Sprague Dawley rats weighing 220g-260g; the transplantation site was the posterior knee joint pulley; the purpose of the transplantation instrument used was to produce a transplant bone bed with a diameter of 2mm and an allogeneic osteochondral graft with a diameter of 2mm.

[0087] S1. Fabrication of transplanted bone bed: The cartilage defect model of small animals is generally selected at the posterior knee joint pulley (see Figure 7 ) is used. The surface of cartilage is very smooth, so a sharp-bottomed manual bone drill (see Figure 8 ) Locate the recipient knee joint pulley articular cartilage (see Figure 7 ), manually rotate the bone drill to create a circular cartilage defect (see Fig. 9 ).

[0088] Subsequently, a flat-bottomed manual bone drill was used to grind the cartilage defect (see Fig.10 ) to make it into the cylindrical defect required by the model. The cartilage and subchondral bone of small animals are relatively fragile. With the help of the handle to apply force, the bone drill can easily drill into it, and finally form a cylindrical transplant bone bed (see Fig.11During this process, repeated flushing with saline is required to keep the cartilage moist and to flush out bone debris and blood. During the modeling process, the depth of the transplanted bone bed is roughly measured using the scale value at the drill bit, and then the depth of the transplanted bone bed is accurately measured using a measuring rod. A sterile marker is used to mark the 12 o'clock and 3 o'clock positions (this operation is to achieve consistency in the external view of the graft), and the values ​​are recorded.

[0089] S2. Graft acquisition: Find the position of the donor knee joint pulley that corresponds to the recipient graft bone bed (see Fig.12 ), use a multifunctional transplanter to align the donor healthy cartilage, and use a sterile marker pen to mark at 12 o'clock and 3 o'clock to facilitate the shape matching when the graft is implanted. Use a hammer to hit the handle or press the handle manually to obtain the graft.

[0090] S3. Implantation of graft: The multifunctional measuring device is inserted into the multifunctional transplanter through the through hole 406 at the handle end. The scale mark line 303 in the multifunctional measuring device and the graft scale value 403 in the middle of the bone extractor can be used to measure the graft thickness. If the graft thickness is too long, gently push the multifunctional measuring device until the graft thickness is consistent with the depth of the graft bone bed, and stop. Use scissors or a scalpel to remove the excess subchondral bone at the conical opening 401. Subsequently, the conical opening 401 of the multifunctional transplanter is aligned with the graft bone bed, and the 12 and 3 o'clock directions of the graft correspond to the 12 and 3 o'clock directions of the graft bone bed. The graft is completely inserted into the graft bone bed under the push of the multifunctional measuring device, and the graft matches the shape of the graft bone bed (see Fig.13 ).

[0091] Micro-CT scans showed that the graft was successfully matched with the bone bed (see Fig.14 ), and the two-dimensional and three-dimensional images showed that the graft completely filled the graft bone bed (see Fig.15 ).

[0092] In addition, the present invention prepared osteochondral transplantation models with a diameter of 1 mm at the trochlear part of the knee joint of rats and mice (see Fig.16 , 17 ), all achieved perfect implantation, and the graft successfully matched the shape of the graft bone bed. Effects of this embodiment:

[0093] This embodiment provides a completely new set of cartilage modeling and transplantation instruments for small animals.

[0094] The kit of this embodiment is precisely processed, and the diameter of the mouse osteochondral graft that can be transplanted is 0.5-1mm, and the diameter of the rat osteochondral graft is 0.5-2mm. The thickness of the graft can be trimmed according to the depth of the transplanted bone bed by a multifunctional transplanter, so that the thickness and shape of the graft are perfectly matched with the depth of the transplanted bone bed.

[0095] The entire process of the kit instrument in this embodiment is manual modeling, not power sampling. First, the knee joint of mice is small and the bone is fragile, so it is easy to pierce it with a power drill, and it is difficult to control the depth of the transplanted bone bed. Second, the power drill will cause thermal damage to the healthy cartilage and allograft around the transplanted bone bed. Compared with manual sampling, power sampling has been proven to reduce the vitality of chondrocytes.

[0096] The handles and rods of all instruments in the embodiment kit are detachable. If a reamer or a bone extractor is damaged, the corresponding rod can be replaced after being detached, thereby reducing costs.

[0097] The kit of the embodiment can perfectly overcome the three major difficulties in existing osteochondral transplantation in small animals: (1) The knee joint of mice is small, and the graft obtained is even smaller, which often makes it difficult to trim and process the graft. (2) Osteochondral grafts are particularly fragile, and using clamping tools such as tweezers may damage the graft. (3) It is difficult to match the shape of the graft with the transplanted bone bed. If the shape of the graft and the transplanted bone bed does not match when the allogeneic graft is implanted, the recipient joint function cannot be restored, and the transplantation will eventually fail.

[0098] The kit instrument of the embodiment includes but is not limited to allogeneic osteochondral transplantation, and can perform the following operations, including tissue engineering technology, autologous osteochondral transplantation, xenogeneic osteochondral transplantation, etc.

Claims

1. A small animal allogeneic osteochondral transplantation device, for the extraction and implantation of micro-osteochondral grafts of small animals, characterized by: It includes a small animal defect model making device and an allogeneic osteochondral graft extraction and implantation device; The small animal defect model making device comprises a pointed-bottom manual bone grinding drill and a flat-bottom manual bone grinding drill; the pointed-bottom manual bone grinding drill is used to make a preliminary small animal defect model; The flat-bottom manual bone grinding drill is used to level and shape the small animal defect model; The allogeneic osteochondral graft extraction and implantation device comprises a multifunctional implanter and a multifunctional measuring device; The multifunctional transplanter is used to extract allogeneic osteochondral transplants; The multifunctional measuring device measures the depth of the small animal defect model and pushes the allogeneic osteochondral graft extracted from the multifunctional transplanter into the small animal defect model.

2. The small animal allogeneic osteochondral transplantation device according to claim 1, characterized in that: The pointed-bottom manual bone grinding drill comprises a pointed-bottom reamer and a handle; The pointed bottom reamer is detachably connected to the handle in a perpendicular manner; The outer surface of the cutter head of the pointed bottom reamer is provided with scales.

3. The small animal allogeneic osteochondral transplantation device according to claim 1, characterized in that: The flat-bottom manual bone grinding drill comprises a flat-bottom reamer and a handle; The flat bottom reamer is detachably connected to the handle in a perpendicular manner; The flat bottom reamer has scales on its outer surface.

4. The small animal allogeneic osteochondral transplantation device according to claim 3, characterized in that: The outer diameter of the flat-bottom reamer is the same as the outer diameter of the pointed-bottom reamer of the pointed-bottom manual bone grinding drill.

5. The small animal allogeneic osteochondral transplantation device according to claim 1, characterized in that: The multifunctional transplanter comprises a transplant extraction part and a handle; The graft extraction piece is a hollow structure; The graft extraction member is detachably connected to the handle in a perpendicular manner to each other; The graft extractor has scales on its outer surface at the head.

6. The small animal allogeneic osteochondral transplantation device according to claim 5, characterized in that: The graft extraction member has a graft thickness measuring portion in the middle thereof; The graft thickness measuring part is provided with a 0 reference line and scales.

7. The small animal allogeneic osteochondral transplantation device according to claim 6, characterized in that: The multifunctional measuring device comprises a measuring rod and a handle; The measuring rod is detachably connected to the handle in a perpendicular manner; The outer surface of the head of the measuring rod is provided with scales; The outer diameter of the measuring rod is not greater than the inner diameter of the hollow structure of the graft extraction piece.

8. The small animal allogeneic osteochondral transplantation device according to claim 7, characterized in that: The measuring rod also has a 0 reference line on its outer surface; When the measuring rod is completely inserted from the handle end into the hollow structure of the graft extraction piece, the 0 reference line coincides with the 0 reference line on the graft thickness measuring part.

9. The small animal allogeneic osteochondral transplantation device according to claim 6, characterized in that: The outer diameter of the flat-bottom reamer of the flat-bottom manual bone grinding drill is the same as the inner diameter of the hollow structure of the graft extraction piece.

10. A method for using a small animal allogeneic osteochondral transplantation device as claimed in any one of claims 1 to 9, characterized in that: The following steps are included: S1. Obtain small animal defect models using a pointed-bottom manual bone drill and a flat-bottom manual bone drill; S2. Obtain the transplanted tissue through the multifunctional transplanter; S3. Determine the thickness of the graft using a multifunctional measuring device and push it into the small animal defect model via a multifunctional transplanter.

Images