WO2005070340A1

WO2005070340A1 - Tendon or ligament tissue regenerator

Info

Publication number: WO2005070340A1
Application number: PCT/JP2005/000740
Authority: WO
Inventors: Hideaki Kagami; Kunihiko Okada; Naoya Yazaki; Nobutoshi Doi; Daisuke Fukuda; Tetsutaro Kikuchi
Original assignee: Nipro Corporation; Ueda, Minoru
Priority date: 2004-01-23
Filing date: 2005-01-21
Publication date: 2005-08-04
Also published as: JP4793985B2; JPWO2005070340A1

Abstract

A tendon or ligament tissue regenerator that as a substitute for conventional tendon or ligament tissue regenerator, excels in strength and flexibility and can realize clinically complete tissue regeneration. There is provided a tendon or ligament tissue regenerator involving an improvement to a tubular material of mesh structure having a lengthwise hollow portion, formed by a filamentous material being a molding of a biodegradable material. Further, there is provided a tendon or ligament tissue regenerator involving an improvement to planiform fabrication of the tubular material. Still further, there is provided a tendon or ligament tissue regenerator, the regenerator in its entirety sewn with a filamentous material being a molding of a biodegradable material. As a result, rapid regeneration of tendon or ligament tissue can be effected, and a tendon or ligament tissue regenerator excelling in bioabsorptivity and not leaving any residual foreign matter in the living body has been made available.

Description

Specification

Tendon or ligament tissue regeneration device

Technical field

The present invention relates to a device for regenerating tendon or ligament tissue, and more particularly, to a device for regenerating human tendon or ligament tissue cut for lesion or injury.

[0002] The present application claims priority from Japanese Patent Application No. 2004-015025, which is incorporated herein by reference.

Background art

[0003] Ligament injury is one of the most frequent diseases related to sports-related trauma.

If ligament damage is left unchecked, it can lead to more serious damage, such as cartilage or joint crescent damage that can only be caused by pain and movement disorders. As the tendon damage, the tearing power of the Achilles tendon is well known. The most widely used treatment for cases requiring tendon or ligament reconstruction is autologous tissue transplantation. Regarding the transplantation of autologous tissue, clinical success has been relatively good, but the harmful and insufficient collection site and insufficient length and strength have required new artificial transplantation materials.

[0004] There are many proposals for artificial graft materials. For example, an absorbent artificial tendon finished in a braided shape (Patent Document 1), an artificial ligament in which a bundle of fiber yarn is spirally wound with a biodegradable absorbent fiber yarn (Patent Document 2), a multilayer spiral Fully absorbable prosthesis in roll form (Patent Document 3), the first component of which is a woven fabric and the second component is an implantable product made of a material capable of inoculating and supporting cell growth (Patent Document 4) ). All of them use a cylindrical one made of biodegradable material as a regenerating device, but there were serious problems in strength and flexibility. In addition, these regenerators have not been fully regenerated. There are also literatures describing the prospects for artificial tendons and ligaments (Non-Patent Document 1).

Patent Document 1: JP-A-51-148289

Patent Document 2: Japanese Utility Model Application Laid-open No. 2-84613

Patent Document 3: JP-A-7-250889 Patent Document 4: JP 2003-512896 A

Non-patent document 1: “Artificial ligament” Orthopedic surgery M〇OK No. 58 1989

Disclosure of the invention

Problems to be solved by the invention

[0006] The present invention replaces a conventional tendon or ligament tissue regeneration device with excellent strength and flexibility, and enables clinically complete tissue regeneration. Is to provide.

Means for solving the problem

[0007] The inventors of the present invention have conducted various studies in consideration of the above circumstances, and found that as a tendon or ligament tissue regeneration device, a longitudinal hollow space formed of a thread-like material molded of a biodegradable material was used. In addition to the improvement to the cylindrical body of the mesh structure having a portion, the improvement to the cylindrical body being prepared into a flat shape, and the entire device is sewn with a thread-like material molded from a biodegradable material. As a result, a tendon or ligament tissue regeneration device that rapidly regenerates tendon or ligament tissue and has excellent bioabsorbability and that does not leave residual foreign matter in the living body has been completed.

That is, the present invention consists of the following.

1. A mesh-shaped cylindrical body having a longitudinal hollow portion formed of a thread-like material molded of a biodegradable material, and a thread molded of a biodegradable material in the longitudinal direction of the hollow portion. A tendon or ligament tissue regeneration device filled with a bundle of objects.

2. A tubular body with a mesh structure having a longitudinal hollow portion formed of a thread-like material molded of a biodegradable material, and a thread molded of a biodegradable material in the longitudinal direction of the hollow portion. A tendon or ligament tissue regeneration device filled with a bundle of fibrous materials, wherein the whole device is sewn by a thread formed of a biodegradable material.

3. The tendon or ligament tissue regeneration device according to the above 1 or 2, wherein the volume filling ratio of the bundle of the filaments to be filled in the cylindrical body is about 50 to 90%.

4. The tendon or ligament tissue regeneration device according to any one of items 1 to 3, wherein the tubular body has a flat shape. 5. The biodegradable material for molding the filamentous material is collagen, polylactic acid, polyglycolic acid, a copolymer of glycolic acid and lactic acid, a copolymer of lactic acid and _ε -aminocaproic acid, polyhydroxy acid, poly (ε —The tendon or ligament tissue regeneration device according to any one of the above items 1 to 4, wherein the device is selected from the group consisting of (force prolatatam) and polyamino acids.

6. The tendon or ligament tissue regeneration device according to the above item 5, wherein the thread is a single yarn or a composite yarn formed by combining single yarns.

7. The tendon or ligament tissue regeneration device according to the above item 6, wherein the composite yarn is any of the following.

1) A total of 2 to 200 single yarns composed of the same type of biodegradable material.

2) A total of 2 to 200 single yarns composed of different biodegradable materials.

8. The tendon or ligament tissue regeneration device according to item 7, wherein the heterogeneous biodegradable material is a combination of a single yarn formed of collagen and a single yarn formed of a biodegradable material other than collagen.

9. A flattened tendon or ligament tissue regeneration device that has a longitudinal direction and is prepared by combining a total of 2 to 200 single yarns formed of collagen and polylactic acid. Is a flat cylindrical body with a mesh structure formed of a composite yarn having a hollow portion in the longitudinal direction, and a single yarn formed of collagen and a single yarn formed of polylactic acid are formed in the hollow portion. A tendon or ligament tissue regeneration device characterized by being filled with a bundle of composite yarns prepared by combining 200 yarns.

10. The entire device is sewn with a composite yarn prepared by combining a total of 2 to 200 single yarns made of collagen and Ζ or polylactic acid. The tendon or ligament tissue regeneration device according to claim 1.

11. The method for producing a tendon or ligament tissue regeneration device according to any one of the above items 1 to 10.

12. By knitting a thread formed from a biodegradable material, a tubular body having a mesh structure having a longitudinal hollow portion is obtained, and a thread formed from a biodegradable material is formed in the longitudinal direction of the hollow portion. Filling the bundle of objects, and further sewing the entire cylindrical body with a thread formed from a biodegradable material, thereby preparing the cylindrical body into a flat shape. Production method.

13. Tendon or ligament tissue regeneration using the tendon or ligament tissue regeneration device described in 1 above Method.

14. Use of the tendon or ligament tissue regeneration device described in 1 above for regeneration of tendon or ligament tissue.

The invention's effect

[0009] The tendon or ligament tissue regeneration device of the present invention is excellent in strength and flexibility, and is a tendon or ligament tissue regeneration device that enables clinically complete tissue regeneration. Brief Description of Drawings

FIG. 1 is a diagram showing an embodiment of the present invention.

FIG. 2 is a schematic diagram of ligament regeneration using the tendon or ligament tissue regeneration device of the present invention.

FIG. 3 is a photograph of the femur and tibia of a rabbit immediately after suturing a tendon or ligament tissue regeneration device.

[Figure 4] A photograph of the regenerated ligament 5 months after suturing the tendon or ligament tissue regeneration device

[0011] 11 ··· Hollow tubular body

12Bunch of thread

21 · · · Tendon or ligament tissue regeneration device

22 ... Surgical thread

23 bone

24 ··· Holes drilled

BEST MODE FOR CARRYING OUT THE INVENTION

[0012] The tendon or ligament tissue in the present invention is exemplified by tendons or ligaments of human primates, non-human primates or rodent animals.

[0013] In the present invention, the tendon or ligament tissue regeneration device uses a thread-like material that is entirely formed of a biodegradable material. The basic configuration includes a cylindrical body having a mesh structure having a hollow portion in the longitudinal direction, and a bundle of filaments is filled in the longitudinal direction of the hollow portion. This mesh structure is one of the essential features of the present invention, and is a factor in the flexibility of the reproduction device. Achieve superiority. The density of this mesh structure depends on the diameter of the thread to be formed, which will be described later. Generally, the knitting density force is 5 to 20 m, preferably 8 to 15 m in the longitudinal direction, and the circumferential direction. 15 to 35 m, preferably 20 to 30 m. The mesh body can be easily produced with a commercially available knitting machine.

[0014] Another essential feature of the present invention is that a tubular body having a mesh structure in which a bundle of filaments is filled in a hollow portion in a longitudinal direction has a flat shape. The flat shape means that, for example, after a cylindrical body is filled with a bundle of filaments, an appropriate pressure is applied to the side of the cylindrical body, that is, at right angles to the longitudinal direction, and the circular cylindrical body is flattened. This is achieved by forming a cylindrical body. The flattening of the tubular body achieves superior strength of the regenerative appliance. The shape of the flat cylindrical body can be selected at any time depending on the tissue to be regenerated, that is, the tendon or ligament. For example, in the case of a tendon regeneration device, the minor axis is about 0.2 mm to about 5 mm, preferably about 0.5 mm to about 3 mm, The major axis is about 0.5 mm to about 50 mm, preferably about lmm to about 30 mm. In the case of a ligament regeneration device, the minor axis is about 0.2 mm to about 2 mm, preferably about 0.5 mm to about 1.5 mm, and the major axis is about 2 mm. —About 15 mm, preferably about 3 mm—about 10 mm.

[0015] Further, another essential feature of the present invention is that the whole device, which is a tubular structure having a mesh structure in which a longitudinal hollow portion is filled with a bundle of thread-like materials, is molded from a biodegradable material. It is sewn with a thread. In particular, it is preferable to sew a flat cylindrical body. Sewing can be achieved, for example, by sewing with a device such as a sewing machine at regular intervals so as to cross the longitudinal direction. This sewing achieves an advantage in the strength of the reclaimed appliance. Here, the constant interval is, for example, 1 mm to 10 mm, particularly preferably 1.5 mm to 8 mm, and the sewing machine pitch for sewing is 0.5 mm to 2 mm, particularly preferably 0.7 mm to 1.5 mm. The instrument for regenerating tendon or ligament tissue of the present invention can be cut to an appropriate length, and then sewn and finally finished with a thread formed of a biodegradable material at the end. The product is completed, for example, by neutralization, washing and air drying. Further, if desired, gamma ray sterilization or the like can be performed.

[0016] The bundle of filaments to be filled in the tubular body has a volume filling ratio of about 50-90%, more preferably 50-80%, in the tubular body. The number of bundles of filaments depends on the diameter defined below, which is generally 300-900 filaments, more preferably 400-750 filaments. is there. For example, winding a thread around a hollow square frame, rotating it a desired number of times, removing it from the frame, and cutting the end, a bundle consisting of twice as many filaments as the number of windings is prepared. . The method of filling the bundle is not particularly limited, but, for example, after preparing a bundle of filamentous material, winding a mesh-structured sheet prepared from a filamentous material molded in advance with a biodegradable material. May be used. Alternatively, a circular cylindrical body having a mesh structure having a longitudinal hollow portion prepared from a thread-like material molded in advance from a biodegradable material was prepared, and the diameter was adjusted to allow the hollow portion to enter. It is also possible to import a bundle of thread-like materials.

[0017] The length of the tubular body may be long as long as it is folded and used. However, if it is cut to an appropriate length from the length of a ligament or tendon of a person for each use purpose, for example, Good. For example, a tendon or ligament tissue regeneration device having an outer shape selected from the following is a preferred embodiment.

1) In the case of a tendon tissue regeneration device, the length in the longitudinal direction is about 10 mm to about 1000 mm, more preferably about 20 mm to about 800 mm, and the width is about 0.5 mm to about 50 mm, and more preferably about lmm to about 32 mm. .

2) In the case of a ligament tissue regeneration device, the longitudinal length is about 10 mm to about 500 mm, more preferably about 50 mm to about 400 mm, and the width is about 2 mm to about 15 mm, and more preferably about 3 mm to about 10 mm.

[0018] The thread used in the present invention is formed of a biodegradable material. A biodegradable material is a material that is degraded by a decomposing enzyme, acid or alkali in a living body, and is characterized by allowing permeation of bodily fluids. For example, known materials can be widely used as biodegradable materials, and commercially available filaments or filaments prepared by a known method can be used. Suitable biodegradable materials include collagen, polylactic acid, polydalicholic acid, copolymers of glyconoleic acid and lactic acid, copolymers of lactic acid and ε-aminocaproic acid, polyhydroxy acids, poly (ε-coprolatatam), and Selected from polyamino acids.

The origin of the collagen used in the present invention is not particularly limited, but generally includes cows, pigs, birds, fish, primates, rabbits, sheep, rats, humans, and the like. Collagen can be obtained from these skins, tendons, bones, cartilage, organs, etc. by various known extraction methods. Although not limited to these specific sites. Furthermore, the type of collagen used in the present invention is not limited to a specific classifiable type, but from the viewpoint of handling, types I, III, and IV are preferred.

[0019] The thread is a single yarn or a composite yarn obtained by combining single yarns.

The single yarn can be suitably used as long as sufficient strength is obtained. The diameter of the single yarn is about 5 μm to about 100 μm, more preferably about 10 μm to 80 μm.

As the single yarn, commercially available single yarns can be widely used. As an example of a suitable material, a collagen single yarn can be used, and the collagen single yarn can be prepared by, for example, extruding a collagen solution. As a solvent for dissolving collagen, any known substance may be used, but water is preferably used according to a conventional method. The concentration of the collagen solution is 0.1-30 wt%, preferably 0.5-10 wt%. The extrusion molding method for producing collagen fibers is not particularly limited, but usually, the coagulation bath is ethyl alcohol, and the extrusion speed is about 100 mm to 500 mm / sec. Cooling of the fiber taken out of the coagulation bath is good if the temperature is below about 40 ° C at which collagen denaturation occurs, but it is preferably kept at 4 ° C to 20 ° C. The fiber diameter is about 5 μm-100 / im, preferably about 10 μm-80 μm.

[0020] Further, in order to adjust the degradability in a living body or to increase the strength, a composite yarn obtained by combining single yarns is more preferable. The composite yarn consists of a total of 2 to 200, preferably 2 to 30, single yarns. There is no particular limitation, such as creating a striated yarn by staking only the yarn and using the remaining single yarn as an aggregate.

Therefore, the composite yarn is any of the following.

1) A combination of a total of 2 to 200, more preferably 2 to 30, single yarns made of the same kind of biodegradable material.

2) A combination of a total of 2 to 200, more preferably 2 to 30, single yarns made of different biodegradable materials.

In the case of the same kind, the composite yarn may be obtained by simply assembling the above collagen single yarn, polylactic acid single yarn, etc., in a single product, preferably a total of 2 to 200, preferably 2 to 30, or a commercially available yarn twisting machine. It is prepared as a combined loose yarn. Garments should be adjusted for the strength or dissolution time of Achieve the superiority of regularity. In the case of different types, the composite yarn is prepared by combining different single yarns, and preferably a total of 2 to 200 yarns, preferably 2 to 30 yarns, or by competing with each other. This enables detailed control of the decomposition time. For example, a combination of a collagen single yarn and a polylactic acid single yarn has the property of decomposing immediately if the ratio of the collagen single yarn is high, and has a property that it is easily decomposed and remains in the body for a long time if the ratio of polylactic acid single yarn is high. . A preferred embodiment of the present invention is a combination of single yarns made of different types of biodegradable materials, that is, a combination of a single yarn formed of collagen and a single yarn formed of polylactic acid.

[0021] In addition, commercially available single yarns or loose yarns can be widely used. For example, a single yarn of polylactic acid (trade name: Ratatron, manufactured by Monofilament Kanebo Synthetic Co., Ltd.), a loose yarn composed of six single yarns of polylactic acid (trade name: Ratatron, manufactured by Multifilament Kanebo Synthetic Co., Ltd.) and the like are exemplified.

[0022] In a preferred embodiment of the tendon or ligament tissue regeneration device of the present invention, a flattened tendon or ligament tissue regeneration device having a longitudinal direction is used. A flat cylindrical body having a mesh structure formed of a composite yarn prepared by combining a total of 2 to 200, more preferably 2 to 30 molded single yarns, and having a hollow portion in a longitudinal direction, The hollow portion is filled with a bundle of composite yarns prepared by combining a total of 2 to 200, more preferably 2 to 30 single yarns formed from collagen and polylactic acid. A tendon or ligament tissue regeneration device. Further, a preferred embodiment of the present invention provides a device for regenerating tendon or ligament tissue, which is a total of 2 to 200, more preferably a total of 2 to 200 single yarns formed of collagen and Z or polylactic acid. Is a tendon or ligament tissue regeneration device sewn with a composite thread prepared by combining 2-30 pieces.

[0023] The present invention is also directed to a method for producing a tendon or ligament tissue regeneration device as defined above, and in a more preferred embodiment, a filamentous material molded from a biodegradable material is knitted. A cylindrical body having a mesh structure having a hollow portion in a longitudinal direction is obtained, and a bundle of a thread formed of a biodegradable material is filled in the hollow portion in the longitudinal direction, and the entire cylindrical body is biodegradable. This is a method for producing an instrument for regenerating tendon or ligament tissue, which includes a step of preparing a tubular body into a flat shape by sewing with a thread-like material molded from a material. Each of these All the meanings of the wording are referred to in the above description. Example

Hereinafter, the present invention will be described in detail with reference to examples, but the present invention is not limited to these examples.

Example

Type I and type III mixture 7 wt% aqueous solution of 150mL of 99.5 vol% ethanol (manufactured by Wako Pure Chemical Industries, Ltd., special grade) collagen by extruding dehydrated coagulated in 3L coagulation bath, the Kola one Gen single yarn fiber diameter ₅₀ μ πι Obtained.

Three loose yarns (latatron, multifilament Kanebo synthetic fiber) consisting of three collagen single yarns and six polylactic acid single yarns are aligned, and the knitting density is adjusted using a knitting machine (Marui Textile Machinery Co., Ltd.). A hollow mesh of about 10 m in the longitudinal direction and about 27 m in the circumferential direction, 30 mm in length and 4 mm in width was created.

On the other hand, a composite yarn was formed by combining one collagen single yarn and one polylactic acid striated yarn. After winding this composite yarn around a square frame with one side of 40 mm, the end was cut to obtain a bundle of composite yarn.

The bundle of composite yarns was inserted in the longitudinal direction of the hollow portion of the hollow mesh body, crushed into a flat shape, and sewed with a sewing machine using a composite yarn obtained by combining two polylactic acid twine yarns. After cutting the bundle of composite yarns protruding from the mesh body at the end, the end of the mesh body was sewn with a composite yarn combining two polylactic acid friendly yarns.

Fig. 1 shows a specific example.

Experimental Example 1

The one-point supporting tensile strength of the ligament tissue regeneration device obtained in the example was measured by an autograph. Specifically, after immersing the ligament tissue regeneration device in physiological saline for about 15 minutes, the loop made with a 4-0 proline suture at a position 5 mm from the end was used as the upper part of the test piece, and 4_0 The loop was hung on a hook attached to the autograph. The measurement was performed with the part up to 10 mm from the lower end of the test piece fixed with a chuck. As a result, the one-point supporting tensile strength of the ligament tissue regeneration device was about 85N.

[0027] Experimental Example 2 Using the ligament tissue regeneration device obtained in the example, the medial collateral ligament of the rabbit was regenerated. Specifically, after resection of the medial collateral ligament of a rabbit, a 4.5 mm hole was drilled in the femur and tibia. Nylon surgical thread was applied to the end of the ligament tissue regeneration device obtained in the example, inserted into the drill hole, and sutured as shown in Fig. 2 (photograph: Fig. 3). Five months later, ligament regeneration was confirmed, and the regenerated ligament was bonded to the bone (Fig. 4). Here, the femur and the tibia were taken out, and the tensile strength of the regenerated ligament was measured using a tensile tester. The pulling speed was 2 mm / min. As a result, the yield point was 113M and the maximum additional load was 119N. Healthy rabbits have a yield point of 209M and a maximum applied weight of about 200N, but they are sufficiently strong for clinical ligament regeneration.

Industrial applicability

The instrument for regenerating tendon or ligament tissue of the present invention is excellent in strength and flexibility, and provides an instrument for regenerating tendon or ligament tissue which is extremely useful in the medical field.

Claims

The scope of the claims

[1] A cylindrical body having a mesh structure having a longitudinal hollow portion formed of a thread-like material molded of a biodegradable material, and a thread-like shape molded of a biodegradable material in the longitudinal direction of the hollow portion. A tendon or ligament tissue regeneration device filled with a bundle of objects.

[2] A cylindrical body having a mesh structure having a longitudinal hollow portion formed of a thread-like material molded of a biodegradable material, and a thread-like member molded of a biodegradable material in a longitudinal direction of the hollow portion. A tendon or ligament tissue regeneration device filled with a bundle of objects, wherein the entire device is sewn with a thread formed of a biodegradable material.

3. The tendon or ligament tissue regeneration device according to claim 1, wherein a volume filling ratio of the bundle of the filaments to be filled in the cylindrical body is about 50 to 90%.

4. The tendon or ligament tissue regeneration device according to any one of claims 1 to 3, wherein the tubular body has a flat shape.

[5] The biodegradable materials for forming the filamentous material include collagen, polylactic acid, polydalicholic acid, copolymer of glycolic acid and lactic acid, copolymer of lactic acid and _ε -aminocaproic acid, polyhydroxy acid, poly ( The tendon or ligament tissue regeneration device according to any one of claims 1 to 4, wherein the device is selected from ε-force prolatatam) and a polyamino acid.

6. The tendon or ligament tissue regeneration device according to claim 5, wherein the thread is a single yarn or a composite yarn formed by combining single yarns.

[7] The tendon or ligament tissue regeneration device according to claim 6, wherein the composite yarn is any of the following.

8. The tendon or claim according to claim 7, wherein the heterogeneous biodegradable material is a combination of a single yarn formed of collagen and a single yarn formed of a biodegradable material other than collagen. Is a ligament tissue regeneration device.

[9] In a flattened tendon or ligament tissue regeneration device that has a longitudinal direction and is flat, a total of 2 to 200 single yarns formed of collagen and single yarns formed of polylactic acid are combined. Thus, it is a flat cylindrical body having a mesh structure having a hollow portion in the longitudinal direction and formed of a composite yarn prepared in the above-described manner, and in the hollow portion, a single yarn formed of collagen and a single yarn formed of polylactic acid. A tendon or ligament tissue regeneration device, which is filled with a bundle of composite yarns prepared by combining a total of 2 to 200 yarns.

[10] The ninth aspect of the present invention, wherein the entire device is sewn by a composite yarn prepared by combining a total of 2 to 200 single yarns formed of collagen and single yarns formed of Z or polylactic acid. Item 2. The tendon or ligament tissue regeneration device according to item 1.

[11] A method for producing the tendon or ligament tissue regeneration device according to any one of claims 1 to 10.

[12] By knitting a thread formed from a biodegradable material, a tubular body having a mesh structure having a hollow portion in the longitudinal direction is obtained. Filling a bundle of filaments and sewing the entirety of the cylinder with a filament molded from a biodegradable material, thereby preparing the cylinder in a flat shape. A method for manufacturing a regenerative appliance.

[13] A method for regenerating a tendon or ligament tissue using the tendon or ligament tissue regeneration device according to claim 1.

[14] Use of the tendon or ligament tissue regeneration device according to claim 1 for tendon or ligament tissue regeneration.