ADIPOSE TISSUE REGENERATION BASE MATERIAL

Abstract

The present invention aims to provide an adipose tissue regeneration substrate that has high handleability and that enables regeneration of a large volume of adipose tissue in a normal shape. Provided is an adipose tissue regeneration substrate including: a plurality of granular bodies made of a bioabsorbable material, each granular body having an inner space and having on a surface a plurality of openings leading to the inner space; and a bag-shaped body made of a bioabsorbable material, the bag-shaped body having an opening and wrapping the granular bodies.

Claims

1. An adipose tissue regeneration substrate comprising: a plurality of granular bodies made of a bioabsorbable material, each granular body having an inner space and having on a surface a plurality of openings leading to the inner space; and a bag-shaped body made of a bioabsorbable material, the bag-shaped body having openings and wrapping the granular bodies.

2. The adipose tissue regeneration substrate according to claim 1, wherein the granular bodies are ellipsoidal bodies containing polylactic acid or a copolymer of lactic acid and another bioabsorbable material.

3. The adipose tissue regeneration substrate according to claim 1, comprising a sponge-like porous body made of a bioabsorbable material inside each of the granular bodies.

4. The adipose tissue regeneration substrate according to claim 1, wherein the bioabsorbable material constituting the bag-shaped body is polyglycolide, a copolymer of polyglycolide and another bioabsorbable material, or a copolymer of lactic acid and another bioabsorbable material.

5. The adipose tissue regeneration substrate according to claim 1, used for implantation in a defect caused by partial mastectomy.

6. A granular body used for the adipose tissue regeneration substrate according to claim 1, the granular body being made of a bioabsorbable material, having an inner space, and having on a surface a plurality of openings leading to the inner space.

7. The granular body according to claim 6, which is an ellipsoidal body containing polylactic acid or a copolymer of lactic acid and another bioabsorbable material.

8. The granular body according to claim 6, comprising a sponge-like porous body made of a bioabsorbable material inside the granular body.

Description

BRIEF DESCRIPTION OF DRAWINGS

[0042] FIG. 1 is a schematic view of the adipose tissue regeneration substrate of the present invention.

[0043] FIG. 2 is a schematic view of a granular body.

[0044] FIG. 3 is a graph showing measurement results of moldability for a hole-shaped defect.

[0045] FIG. 4 is a graph showing measurement results of moldability for a horizontal defect.

[0046] FIG. 5 shows magnetic resonance images (MRIs) of adipose tissue regeneration substrates obtained in Example 1, taken zero (immediately after implantation), one, three, six, and nine months after implantation in fascial defects of a pig.

[0047] FIG. 6 is an image of a hematoxylin-eosin (HE) stained implantation portion, taken six months after the adipose tissue regeneration substrates obtained in Example 1 were implanted in the fascial defects of the pig.

[0048] FIG. 7 is an image of an oil red O stained implantation portion, taken six months after the adipose tissue regeneration substrates obtained in Example 1 were implanted in the fascial defects of the pig.

[0049] FIG. 8 is an image of an Azan stained implantation portion, taken six months after the adipose tissue regeneration substrates obtained in Example 1 were implanted in the fascial defects of the pig.

[0050] FIG. 9 is an image of anti-CD31 antibody immunostained implantation portion, taken six months after the adipose tissue regeneration substrates obtained in Example 1 were implanted in the fascial defects of the pig.

DESCRIPTION OF EMBODIMENTS

[0051] In the following, embodiments of the present invention are described in detail with reference to examples. The present invention is not limited to these examples.

Example 1

[0052] A collagen sponge (produced by Pelnac, Smith & Nephew Wound Management KK.) was wrapped in a mesh (filament thickness: 0.2 mm to 0.25 mm, mesh opening: 1×1 mm to 2×2 mm) made of polylactic acid (weight average molecular weight: 220,000), and the ends of the mesh were closed by thermal pressure bonding to give an ellipsoidal granular body having the collagen sponge inside and having a major axis of 18 mm and a minor axis of 7.5 mm. Thirty granular bodies were prepared in the same manner. The granular bodies were wrapped in a 110 mm×35 mm bag-shaped body having an envelope shape and made of polyglycolide multifilaments (filament structure: 0.015 mm×12, aperture size: 0.05 mm×0.05 mm). The end of the bag-shaped body was closed by thermal welding, whereby an adipose tissue regeneration substrate was obtained.

Example 2

[0053] An adipose tissue regeneration substrate was obtained as in Example 1 except that no collagen sponge was used.

Comparative Example 1

[0054] The 30 granular bodies of Example 1 were directly used as adipose tissue regeneration substrates.

<Evaluation>

[0055] The adipose tissue regeneration substrates obtained in the examples and the comparative example were evaluated as follows.

(Tissue Regeneration Evaluation 1)

[0056] A subcutaneous incision was made in the back of a miniature pig (about 20 kg). The adipose tissue regeneration substrate obtained in Example 1 or 2 was implanted to the left of the midline. After four months, the portion in which the adipose tissue regeneration substrate was implanted was removed and examined for tissue regeneration. About 4 cm of tissue was regenerated.

(Tissue Regeneration Evaluation 2)

[0057] A miniature pig (about 25 kg), a large animal, was provided as an experimental animal. A median incision was made in the abdominal skin. Subsequently, the adipose and mammary tissue on the left and right sides of the abdomen were removed, and defects were made on the fascia under the mammary gland. In each of the fascial defects was implanted the adipose tissue regeneration substrate obtained in Example 1, and the skin was sutured.

[0058] Magnetic resonance images (MRIs) of the abdomen were taken zero (immediately after implantation), one, three, six, and nine months after surgery. FIG. 5 shows the magnetic resonance images (MRIs).

[0059] Six months after surgery, adipose tissue on the muscular layer on the right side of the abdomen was taken out, and the implantation portion was removed. The obtained specimen was sectioned and subjected to hematoxylin-eosin (HE) staining, oil red O staining, Azan staining, and anti-CD31 antibody immunostaining. The micrographs of the HE stained, oil red O stained, Asan stained, and anti-CD31 antibody immunostained sections are respectively shown in FIG. 6, FIG. 7, FIG. 8, and FIG. 9.

[0060] FIG. 5 demonstrates that six months after surgery, the portions in which the adipose tissue regeneration substrates were implanted showed regeneration of adipose tissue (white portions in the MRI (T1-weighted image in FIG. 5) from the peripheral portions adjoining adipose tissue or mammary tissue. Nine months after surgery, regeneration of adipose tissue was observed in a larger area from the peripheral portion of the adipose tissue regeneration substrate.

[0061] Furthermore, FIG. 6, FIG. 7, and FIG. 8 show that six months after surgery, adipose tissue and collagen tissue were formed inside the adipose tissue regeneration substrate. FIG. 9 shows that blood vessels were formed in this adipose tissue and collagen tissue.

(Evaluation of Moldability)

(1) Moldability for Hole-Shaped Defect

[0062] Unskinned chicken breast (358 g) was provided as a substitute for the skin and adipose tissue. The skin of the chicken breast was partially peeled to expose the meat. Subsequently, a cross-shaped incision was made in the exposed meat, and the center of the incision was hollowed out to form a hole-shaped defect. The skin was put back to the original position before the longitudinal and transverse lengths of the incision and the height of the defect were measured. The adipose tissue regeneration substrate obtained in Example 1 was then implanted in the defect. The skin was put back to the original position, and then the longitudinal and transverse lengths of the incision and the height of the defect were measured.

[0063] Subsequently, the 30 adipose tissue regeneration substrates of Comparative Example 1 were used, and the longitudinal and transverse lengths of the incision and the height of the defect were measured in the same manner. FIG. 3 shows the measurement results. The measurement results show that the adipose tissue regeneration substrates of Comparative Example 1 are difficult to mold in the height direction because they enter the incision, whereas the adipose regeneration substrate of Example 1 is easy to mold into a tall shape because the adipose tissue regeneration substrate does not much spread in a longitudinal or transverse direction, and the granular bodies are close together as if they form a mountain in the height direction. This shows that the adipose tissue regeneration substrate of Example 1 has excellent moldability for adipose tissue of the breasts and the buttocks, for example.

(2) Moldability for Horizontal Defect

[0064] Unskinned chicken breast (379 g) was provided as a substitute for the skin and adipose tissue. The skin was partially peeled to expose the meat. One incision was made along the muscle fiber direction of the exposed meat. The transverse length of the incision, the longitudinal length of the incision when the incision was opened, and the height of the incision were measured. The adipose tissue regeneration substrate obtained in Example 1 was then implanted in the incision, and the longitudinal and transverse lengths and the height of the incision were measured. Subsequently, the 30 adipose tissue regeneration substrates of Comparative Example 1 were used, and the longitudinal and transverse lengths and the height of the incision were measured in the same manner.

[0065] At this time, observation of the states of the implanted adipose tissue regeneration substrates of Example 1 and Comparative Example 1 showed that the adipose tissue regeneration substrate of Example 1 did not protrude from the incision, whereas multiple adipose tissue regeneration substrates of Comparative Example 1 protruded or fell off from the incision. Here, the measurement in Comparative Example 1 was performed after the protruding or fallen adipose tissue regeneration substrates were pushed back into the incision.

[0066] FIG. 4 shows the measurement results. The measurement results show that the adipose tissue regeneration substrates of Comparative Example 1 are difficult to mold in the height direction because they spread in the longitudinal direction of the incision, whereas the adipose tissue regeneration substrate of Example 1 is easy to mold into a tall shape because the adipose tissue regeneration substrate does not much spread in the longitudinal or horizontal direction, and the granular bodies are close together as if they form a mountain in the height direction. This shows that the adipose tissue regeneration substrate of Example 1 has excellent moldability for adipose tissue of the breasts and the buttocks, for example.

INDUSTRIAL APPLICABILITY

[0067] The present invention can provide an adipose tissue regeneration substrate that has high handleability and that enables regeneration of a large volume of adipose tissue in a normal shape.

REFERENCE SIGNS LIST

[0068] 1 Granular body [0069] 2 Sponge-like porous body [0070] 3 Bag-shaped body