JP2007252645A - Transplanted ligament to be used for ligament reconstruction and method of animal ligament reconstruction - Google Patents

Abstract

<P>PROBLEM TO BE SOLVED: To provide a transplanted ligament applicable to a ligament reconstruction method capable of reducing a period of rehabilitation. <P>SOLUTION: The transplanted ligament 3 comprises a transplanted ligament main body 4 and a synovial fluid impermeable film 5 covering the main body 4. The synovial fluid opaque film 5 covers a part of the main body 4 coming in contact with the synovial fluid. For the transplanted ligament main body 4, a well-known artificial ligament or surrogate ligament is used. For the synovial fluid opaque film 5, a high-polymer film is used and a bioabsorbable film is especially preferable. In the case of high-polymer film, a method for covering is carried out only by winding it on the surface of the main body 4. The synovial fluid impermeable film 5 is also covered by applying high-polymer solution on the surface of the main body 4. For the high-polymer solution, bioabsorbable solution is preferable. When the surface of the main body 4 is covered with the film 5, the synovial fluid does not touch the main body 4. Thus, intrusion of a tissue into the main body 4 and engraftment can quickly be performed. <P>COPYRIGHT: (C)2008,JPO&INPIT

Description

  The present invention relates to a transplanted ligament used when a damaged or torn ligament is reconstructed. The present invention also relates to an animal ligament reconstruction method using the transplanted ligament.

  Athletes who perform intense exercise such as soccer, rugby, skiing, American football, and baseball often damage or tear the ligaments of joints such as knees, ankles, and elbows. In addition, not only athletes but also normal people may damage or tear the ligaments. In such a case, in order to return again as an athlete or a member of society, surgery and rehabilitation for ligament reconstruction are performed.

  As a ligament reconstruction method, there are a method using an artificial ligament and a method using a substitute ligament such as an autologous fascia or an autologous ligament. The method of using an artificial ligament has a problem that it is difficult to adapt to one's body because the strength is too high. In addition, although the method using the substitute ligament is easy to adjust to one's body, it takes one year or more for rehabilitation, and it takes too much time to return as an athlete or to return to society.

  For this reason, various developments for shortening the rehabilitation period have been performed while using a substitute ligament. For example, it has been proposed that calcium phosphate is coated on the site of the substitute ligament that comes into contact with the bone, shortening the bond period between the bone and substitute ligament, and shortening the period from the start of surgery to the start of rehabilitation (non-patent) Reference 1). That is, by shortening the period until the start of rehabilitation, an attempt is made to shorten the period from surgery to return.

Announced by National Institute for Materials Science, August 28, 2001 "Succeeded in direct bonding of ligament and bone using apatite compound (reduced rehabilitation period for ligament reconstruction)"

  As described in Non-Patent Document 1, the present inventor did not pay attention to the joint period between bone and the substitute ligament, but focused on the mechanism by which the substitute ligament replaced the ligament-like tissue. That is, the mechanism by which a ligament-like tissue is generated is that cells enter the surrogate ligament, and the cells engraft, differentiate, and align, thereby generating a ligament-like tissue. Therefore, the present inventor first investigated the extent to which cells entered and engrafted into the substitute ligament by repeating animal experiments. In this process, the present inventor discovered the following phenomenon.

  That is, as shown in FIG. 1, the substitute ligament 4 is used to connect the first bone 1 (the femur in the case of the anterior cruciate ligament) and the second bone 2 (the tibia in the case of the anterior cruciate ligament), and one month after the operation. When the number of cells in the surrogate ligament 4 after the lapse of time was measured, as shown in Comparative Example 1 described later, a large number of cells exist at the site a in FIG. 1, but the other b, c, d, and In the part of e, the phenomenon that the number of cells was very small was discovered.

  The present inventor has examined why a large number of cells are present at the site a and only a small number of cells are present at the sites b to e. As a result, in the part a, a part of the substitute ligament 4 is embedded in the first bone 1, whereas the parts b to e are embedded in the first bone 1 and the second bone 2. I thought it was because I did not. Then, it was hypothesized that when the surrogate ligament 4 is in contact with the joint fluid, the entry and engraftment of cells into the surrogate ligament 4 is inhibited.

  In order to examine whether or not such a hypothesis is correct, a site of a to e of the substitute ligament 4 is covered with a synovial fluid impermeable membrane (specifically, a water impermeable film) 5, and first The bone 1 and the second bone 2 were connected, and the number of cells in the substitute ligament 4 after one month after the operation was measured. As a result, it was confirmed that a large number of cells were present at sites a to e (Example 1 described later), and it was proved that the hypothesis was correct. The present invention has been made based on such knowledge.

  That is, the present invention relates to a transplanted ligament used for ligament reconstruction, characterized in that at least a surface of a graft ligament body in contact with joint fluid is coated with a joint fluid-impermeable membrane. The present invention also relates to a method for reconstructing an animal ligament using the graft ligament.

  As the transplanted ligament body used in the present invention, conventionally known substitute ligaments such as autologous fascia, autologous ligament, fascia and ligament of other family are used. Further, not only a substitute ligament but also an artificial ligament can be used. In particular, bioabsorbable artificial ligaments such as collagen, gelatin, silk, or polylactic acid can also be used. Bioabsorbable materials are also generally biodegradable. When the strength in the longitudinal direction of the graft ligament body is weak, it is preferable to add a high-strength yarn to the graft ligament body. For example, it is preferable to use the one in which the periphery of the high-strength yarn 7 is surrounded by the graft ligament body 4 (FIG. 2). Alternatively, the high strength yarn 7 and the graft ligament body 4 may be aligned. As the high-strength yarn, a hydrophobic Teflon yarn that does not absorb body fluid, water or the like is used.

  When this graft ligament body is applied to a person, the surface of the site that comes into contact with the joint fluid is covered with a joint fluid impermeable membrane. The part to be coated is limited to the part that comes into contact with the joint fluid, and other parts may not be covered. Other parts may also be covered with a synovial fluid impermeable membrane. The joint fluid is mainly composed of water and contains other smooth components. Therefore, any synovial fluid impermeable membrane can be used as long as it is a water impermeable membrane made of a polymer film such as a food packaging film.

  Examples of a method for covering a predetermined site of the graft ligament body include the following methods. For example, when the synovial fluid impermeable membrane is a polymer film, the film may be wound around the surface of the graft ligament body to cover it. Moreover, what is necessary is just to adhere | attach both with an adhesive agent when improving the adhesive force of a film and the graft ligament main body surface. As the polymer film, a film made of a natural polymer or a film made of a synthetic polymer is used. Among these, a bioabsorbable polymer film is particularly preferable. That is, it is preferable that the film be absorbed by the living body and disappear when the ligament is reconstructed after the rehabilitation period after surgery. Examples of such bioabsorbable polymer films include biodegradable films made of collagen, gelatin, silk, and polylactic acid. Moreover, although arbitrary things are used also as an adhesive agent, it is preferable to use bioabsorbable adhesive agents, such as starch paste.

  As another coating method, a polymer solution may be applied to a predetermined site on the surface of the graft ligament body and dried to form a film-like material on the surface of the graft ligament body. As a coating method, a known method such as a brush method or a spray method can be employed. As the polymer solution, a solution in which a natural polymer or a synthetic polymer is dissolved or dispersed can be used. Also in this case, it is preferable to prepare a bioabsorbable solution using the bioabsorbable polymer as described above.

  As described above, a graft ligament in which the surface of the graft ligament main body in contact with the joint fluid is coated with the joint fluid impermeable membrane is obtained. Using this transplanted ligament, it is applied to humans and animals by the same surgical method as when a conventional artificial ligament or a substitute ligament is used. FIG. 3 is a schematic view of a state in which the graft ligament 3 according to the present invention is applied to a person by surgery. The graft ligament 3 connects the first bone 1 (femur) and the second bone 2 (tibia), and is fixed to the first bone 1 and the second bone 2 with bolts or the like. The graft ligament 3 according to the present invention includes a graft ligament body 4, a high-strength yarn 7 added to improve the strength of the graft ligament body 4, and a joint covering the surface of the graft ligament body 4. It is comprised with the liquid impervious film | membrane 5. The space between the first bone 1 and the second bone 2 is filled with the joint fluid 6. The surface of the site of the graft ligament 3 that is in contact with the joint fluid 6 is covered with the joint fluid impermeable membrane 5. Therefore, the joint fluid 6 does not contact the graft ligament body 4 and does not inhibit the entry and engraftment of cells from the bone (specifically, bone marrow) into the body 4. Since cells are supplied from the bone marrow, the bone and the graft ligament body 4 are preferably in direct contact. Therefore, it is preferable that both ends of the graft ligament body 4 are not covered with the joint fluid impermeable membrane 5.

  The graft ligament 3 may be created at the time of surgery. For example, at the time of surgery, after preparing the graft ligament body 4 (or the graft ligament body 4 to which the high-strength thread 7 is added) and the synovial fluid impermeable membrane 5 and incising the corresponding part (knee), The dimension in which the joint fluid 6 contacts is confirmed, and the surface of the site of the graft ligament body 4 in contact with the joint fluid 6 may be coated with the joint fluid impermeable membrane 5 in accordance with this dimension. And after that, you may fix the graft ligament 3 to a ligament damage tear part. Further, after fixing the graft ligament body 4 (or the graft ligament body 4 to which the high-strength yarn 7 is added) to the ligament injury rupture portion, the region of the body 4 between the first bone 1 and the second bone 2 (that is, The part where the synovial fluid 6 contacts may be covered with the synovial fluid impermeable membrane 5 and covered.

  The transplant ligament according to the present invention can be applied to humans or animals. Among animals, dogs are irreplaceable for disabled people as service dogs. Therefore, the graft ligament according to the present invention and the ligament reconstruction method using the graft ligament are beneficial when applied to a dog.

  The graft ligament according to the present invention is formed by coating the surface of a graft ligament body such as a substitute ligament with a synovial fluid impermeable membrane. And a covering location is a site | part which contacts at least joint fluid. Therefore, when the graft ligament according to the present invention is applied to a human or an animal and ligament reconstruction is performed, the joint fluid does not come into contact with the graft ligament body. As a result, cells supplied from the bone (bone marrow) to the graft ligament body do not come into contact with the joint fluid and rarely inhibit its entry and engraftment. As a result, the transplanted ligament body is quickly replaced with a ligament-like tissue by autologous cells.

  From the above, if the ligament reconstruction is performed using the transplanted ligament according to the present invention, the rehabilitation period of the ligament reconstruction is shortened, the sport can be returned to early, and the effect of being able to return to society early. It is what you play.

  EXAMPLES Hereinafter, although this invention is demonstrated based on an Example, this invention is not limited to an Example. The present invention is based on the knowledge that when the graft ligament body is in contact with the synovial fluid, the entry and engraftment of cells into the graft ligament body is inhibited, so that the graft ligament body does not contact the synovial fluid. It should be interpreted as something that has been devised.

Comparative Example 1
Patient dog: Beagle 2 years old Male Experimental dog Affected part: Left hind limb Knee cruciate ligament Transplant ligament: The half of the left Achilles tendon (autologous ligament) was used as the graft ligament body. Then, in order to improve the strength, a graft ligament in which Teflon yarn was added and the state shown in FIG. 2 was used was used. The longitudinal length of the graft ligament body was 40 mm.

After completely removing the anterior cruciate ligament of the affected area, this site is replaced with a transplanted ligament and fixed in the state as shown in FIG. 3 (however, the synovial fluid impermeable membrane 5 is not present). went. After the operation, the movement was restricted using a toma fixed frame that can adjust the range of motion of the knee joint. The first week was completely fixed, and then the range of motion was gradually expanded over a month. Then, after 1 month, the affected part was incised, specimens were collected from each site a to e shown in FIG. 1, and the number of cells was measured. The number of cells was measured with an electron micrograph. As a result, as shown in FIG. 4, the number of cells was about 50,000 cells / mm ^{2 at} the site a, but the number of cells was less than 10,000 cells / mm ^{2 at the} sites b to e. It was.

Example 1
Patient dog: Beagle 2 years old Female Experimental dog Affected part: Left hind limb Knee cruciate ligament Transplant ligament: The same one as used in Comparative Example 1 was used. Then, the both ends of the graft ligament body were left 10 mm each, and the center part 20 mm was covered with a joint fluid impermeable film made of a polyethylene film (thickness 20 μm).

After removing the entire anterior cruciate ligament of the affected area, this site was replaced with a transplanted ligament and fixed in the state shown in FIG. 3 to perform ligament reconstruction. After the operation, the movement was restricted using a toma fixed frame that can adjust the range of motion of the knee joint. The first week was completely fixed, and then the range of motion gradually expanded over a month. Then, after 1 month, the affected part was incised, specimens were collected from each site a to e shown in FIG. 1, and the number of cells was measured. The number of cells was measured with an electron micrograph. As a result, as shown in FIG. 4, the number of cells was 40000 cells / mm ² or more at each site, and it was found that cells rapidly entered and were engrafted.

Comparative Example 2
Patient dog: Beagle 2.5 years old Female Experimental dog Affected part: Left hind limb Knee cruciate ligament Transplant ligament: The same one as used in Comparative Example 1 was used.

After completely removing the anterior cruciate ligament of the affected area, this site is replaced with a transplanted ligament and fixed in the state as shown in FIG. 3 (however, the synovial fluid impermeable membrane 5 is not present). went. After the operation, the movement was restricted using a toma fixed frame that can adjust the range of motion of the knee joint. The first week was completely fixed, and the range of motion gradually expanded over the next 20 days. After the lapse of 20 days, the affected part was incised, a specimen was collected from the site b shown in FIG. 1, and the number of cells was measured. The number of cells was measured with an electron micrograph. As a result, as shown in FIG. 5, the number of cells was less than 10,000 cells / mm ² .

Thereafter, the affected area was sutured again and rehabilitation was performed for another 20 days (40 days in total). Then, the affected part was incised again, a specimen was collected from the site b shown in FIG. 1, and the number of cells was measured. As a result, as shown in FIG. 5, the number of cells was less than 10,000 cells / mm ² . Furthermore, the same experiment was repeated every 20 days, and the number of cells after rehabilitation for 60 days and 80 days in total was measured. As a result, as shown in FIG. 5, the number of cells was less than 10,000 cells / mm ² .

Example 2
Patient dog: Beagle 3 years old Female Experimental dog Affected part: left hind limb Knee cruciate ligament Transplant ligament: The same one as used in Comparative Example 1 was used. Then, the both ends of the graft ligament body were left 10 mm each, and the center part 20 mm was covered with a joint fluid impermeable film made of a polyethylene film (thickness 20 μm).

After removing the entire anterior cruciate ligament of the affected area, this site was replaced with a transplanted ligament and fixed in the state shown in FIG. 3 to perform ligament reconstruction. After the operation, the movement was restricted using a toma fixed frame that can adjust the range of motion of the knee joint. The first week was completely fixed, and the range of motion gradually expanded over the next 20 days. After the lapse of 20 days, the affected part was incised, a specimen was collected from the site b shown in FIG. 1, and the number of cells was measured. The number of cells was measured with an electron micrograph. As a result, as shown in FIG. 5, the number of cells was 10,000 cells / mm ² or more. When the specimen was collected, a hole was opened in the synovial fluid impermeable membrane, and starch was adhered to the hole to close the hole.

In the same manner as in Comparative Example 2, the affected area was sutured again, and rehabilitation was further performed for 20 days (40 days in total). Then, the affected part was incised again, a specimen was collected from the site b shown in FIG. 1, and the number of cells was measured. As a result, as shown in FIG. 5, the number of cells was 30000 cells / mm ² or more. At this time, a hole opened in the synovial fluid impermeable membrane, and starch paste was attached to the hole to close the hole. Furthermore, the same experiment was repeated every 20 days, and the number of cells after rehabilitation for 60 days and 80 days in total was measured. As a result, as shown in FIG. 5, the number of cells was 40000 cells / mm ² or more.

It is a schematic diagram of the state which connected the femur and the tibia with the conventional substitute ligament. It is the typical perspective view which showed the example which added the high strength thread | yarn to the graft ligament main body which concerns on this invention. It is a schematic diagram after performing the reconstruction operation of the anterior cruciate ligament in the graft ligament according to an example of the present invention. It is the graph showing the cell number after one month progress in the site | part of ligament ae by the ligament reconstruction method by the comparative example 1 and Example 1. FIG. It is the graph showing the cell number after 20-80 days progress in the site | part of the ligament b by the ligament reconstruction method by the comparative example 2 and Example 2. FIG.

Explanation of symbols

1 First bone (femur)
2 Second bone (tibia)
3 graft ligament 4 graft ligament body 5 synovial fluid impermeable membrane 6 joint fluid 7 high strength thread

Claims (9)

  A graft ligament for use in ligament reconstruction, characterized in that at least the surface of a graft ligament body in contact with joint fluid is coated with a joint fluid impermeable membrane.   The transplanted ligament for use in ligament reconstruction according to claim 1, wherein a portion that does not come into contact with joint fluid is not covered with a synovial fluid impermeable membrane.   The graft ligament used for ligament reconstruction according to claim 1, wherein the graft ligament body is an artificial ligament or a substitute ligament.   The graft ligament used for ligament reconstruction according to claim 1, wherein a polymer film is used as the synovial fluid impermeable membrane.   The graft ligament used for ligament reconstruction according to claim 4, wherein the polymer film is a bioabsorbable film.   The graft ligament used for ligament reconstruction according to claim 1, wherein a synovial fluid impermeable film is formed by applying a polymer solution to the surface of the graft ligament body.   The graft ligament used for ligament reconstruction according to claim 6, wherein the polymer solution is a bioabsorbable solution.   After preparing the graft ligament and the joint fluid impermeable membrane, at least the surface of the graft ligament that contacts the joint fluid is coated with the joint fluid impermeable membrane and fixed to the ligament injury rupture part of the animal An animal ligament reconstruction method characterized by the above.   The animal ligament reconstruction method according to claim 8, wherein the animal is a dog.

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