JP4522124B2 - Periodontal tissue regeneration material - Google Patents

Description

  The present invention relates to a periodontal tissue regeneration material comprising a collagen thread and a biodegradable polymer coating layer provided on the surface of the collagen thread, a manufacturing method, a method of use, and a preparation kit.

  Dental plaque (plaque) adhering to the tooth surface is a mass of bacteria, so that more than 70% of it is occupied by caries or periodontal fungi. Periodontal tissue causes an inflammatory reaction due to bacteria in the plaque and loses connective tissue attachment to the root. The place where this connective tissue adhesion is lost is because the gingival epithelium (epithelial cells) has a faster regeneration rate than that of other periodontal tissues represented by alveolar bone (osteoblasts). Growth is healed in the form of a junctional epithelial attachment, forming grooves called periodontal pockets around the teeth. Due to this periodontal pocket, plaque is more likely to accumulate and a vicious cycle of causing an inflammatory reaction again is repeated, and periodontal tissue that supports the teeth is lost. This is a symptom of periodontal disease, and there is a risk that the teeth will eventually fall out. Furthermore, even when a denture is mounted or implanted as a substitute for a tooth that has fallen, it is difficult to carry out the procedure in a state where the periodontal tissue that forms the basis of the tooth is lost.

  In recent years, the GTR (Guided Tissue Regeneration) method has attracted attention in the periodontology field. This creates a space for the surgical regeneration of the desired periodontal tissue between the gingiva and root, creating a healing response in the form of a new attachment, while the lid is covered by a membrane that blocks the gap. In this method, the invasion of the gingival epithelium, that is, the downgrowth is inhibited. The GTR method is a method of promoting periodontal tissue regeneration by securing a space for regeneration of the periodontal tissue while preventing downgrowth of the gingival epithelium using a blocking membrane (GTR membrane). Conventionally, a semi-permeable membrane such as a tetrafluoroethylene porous material or a polyester filter has been used as the GTR membrane. However, since these GTR membranes are not decomposed and absorbed in the living body, they need to be removed after the operation and do not adhere to the full thickness of the gingival flap.

  On the other hand, when a biodegradable material such as collagen, polylactic acid, or oxidized cellulose is used as a material for the GTR film, the time for the GTR film to decompose is faster than the time for the periodontal tissue to completely regenerate, There was a problem such as weakness.

  In addition, the GTR film so far is only for securing a “space” for the periodontal tissue to regenerate as described above, and the regeneration of the tissue itself is left to self-healing power. Therefore, it has been impossible to repair a horizontal bone defect, which is a severe alveolar bone defect, for example, with the current GTR membrane.

  Furthermore, the current GTR method has a problem in the surgical technique that it is difficult to handle the GTR film at the time of surgery. Since the surgical procedure itself is an effective method, the skill of the surgeon tends to be a factor in determining whether the surgery is right or wrong, and a GTR film that is easy to handle has been demanded.

  In order to solve such a problem, a GTR film excellent in decomposition resistance and strength has been developed (Patent Document 1). Furthermore, when a damaged part is large, the technique which reproduces | regenerates a structure | tissue by using together the fixing tool formed with the biodegradable material is also developed (patent document 2). However, no results regarding periodontal tissue regeneration when these barrier films are used are disclosed.

JP-A-7-265337 JP-A-8-191843

  Therefore, it has excellent resistance to degradation, strength and user-friendliness, and it has a periodontal tissue regeneration ability that can cope with severe periodontal tissue damage that had to be given up in the clinical setting. There is a need to develop materials for regenerating peri-tissue.

The present invention
(1) A periodontal tissue regeneration material comprising a composite thread having a collagen thread and a biodegradable polymer coating layer formed on the surface of the collagen thread,
(2) The periodontal tissue regeneration material according to (1), wherein the composite filamentous material is molded into a porous body,
(3) The periodontal tissue regeneration material according to (2), wherein the communicating porous body is a film having a thickness of about 0.05 to 70 mm,
(4) The periodontal tissue regeneration material according to (1), wherein the outer diameter of the collagen filamentous material is about 5 to 70 μm,
(5) The periodontal tissue regeneration material according to (1), wherein the biodegradable polymer is polylactic acid, collagen, polyglycolic acid, polysaccharide, biodegradable polyester or polypeptide,
(6) The periodontal tissue regeneration material according to (1), wherein the biodegradable polymer is polylactic acid,
(7) A periodontal tissue regeneration material comprising a composite filamentous material obtained by mixing a collagen filamentous material with a biodegradable polymer solution and drying it as it is,
(8) Obtained by seeding and culturing cells on a periodontal tissue regeneration material composed of a composite filamentous material having a collagen filamentous material and a biodegradable polymer coating layer formed on the surface of the collagen filamentous material. Periodontal tissue regeneration material,
(9) The cells are mesenchymal stem cells, epithelial stem cells, hematopoietic stem cells, vascular endothelial stem cells, neural stem cells, hepatic stem cells, inner ear stem cells, pancreatic stem cells, osteoblasts, periosteal cells, fibroblasts, embryonic stem cells or somatic Periodontal tissue regeneration material according to (8), which is a stem cell,
(10) A method for producing a periodontal tissue regeneration material, comprising mixing a collagen thread and a biodegradable polymer solution, and drying the mixture as it is,
(11) Seeding and culturing cells in a periodontal tissue regeneration material comprising a composite filamentous material having a collagen filamentous material and a biodegradable polymer coating layer formed on the surface of the collagen filamentous material. A method for producing a periodontal tissue regeneration material,
(12) A periodontal tissue regeneration material composed of a composite thread having a collagen thread and a biodegradable polymer coating layer formed on the surface of the collagen thread is adapted to a periodontal tissue defect, Periodontal tissue regeneration method characterized by covering and fixing the gingival flap around the periodontal tissue defect,
(13) Obtained by seeding and culturing cells on a periodontal tissue regeneration material composed of a composite filamentous material having a collagen filamentous material and a biodegradable polymer coating layer formed on the surface of the collagen filamentous material. Periodontal tissue regeneration method characterized by adapting the obtained periodontal tissue regeneration material to a periodontal tissue defect, covering with a gingival flap around the periodontium defect, and fixing with suture
(14) A continuous porous body having a planar membrane shape having a thickness of about 0.05 to 2 mm, comprising a composite filamentous material having a collagen filamentous material and a biodegradable polymer coating layer formed on the surface of the collagen filamentous material. The periodontal tissue regeneration material molded into a periodontal tissue regeneration method, characterized in that it is used as a blocking means for maintaining a space for regeneration of the periodontal tissue, and
(15) The present invention relates to a preparation kit for periodontal tissue regeneration comprising a collagen filamentous material and a biodegradable polymer solution.

  The periodontal tissue regeneration material of the present invention is a good scaffold material for periodontal tissue regeneration, and can be applied to severe periodontal tissue damage that had to be abandoned in conventional clinical settings. It has regenerative ability and has excellent resistance to decomposition and absorption. Further, the periodontal tissue regeneration material can be used as a barrier film (GTR film) that has been used in the conventional GTR method, and is extremely excellent in strength.

  The periodontal tissue regeneration material of the present invention is characterized by comprising a composite filamentous material having a collagen filamentous material and a biodegradable polymer coating layer formed on the surface of the collagen filamentous material. As the form of the periodontal tissue regeneration material, a bundle in which composite filaments are arranged in parallel, a porous body in which three-dimensionally irregularly arranged porous bodies are selected, but a porous body is preferable, and a thickness of about A porous body molded into a flat film shape of 0.05 to 70 mm, particularly preferably a porous body molded into a flat film shape with a thickness of about 0.1 to 50 mm. Here, the communicating porous body means that the structure having a plurality of voids having a uniform or non-uniform size when dispersed under visual observation is continuously dispersed, and is a structure in which at least one section communicates. .

  The outer diameter of the collagen filamentous material of the present invention is not particularly limited as long as it has flexibility. However, the smaller the diameter, the larger the surface area of the fiber, and thus better cell engraftment and growth. Can be expected. Also, in terms of ease of shape provision, a smaller diameter is preferable because it can flexibly follow the shape of the affected area. The outer diameter is about 5 to 70 μm, preferably about 5 to 30 μm, and more preferably about 10 to 15 μm.

  Examples of the collagen used include enzyme-solubilized collagen, acid-solubilized collagen, alkali-solubilized collagen, and neutral-solubilized collagen. These solubilized collagens are collagens that have been treated so that they can be dissolved in a solvent. Examples thereof include solubilized collagen such as acid-solubilized collagen, alkali-solubilized collagen, enzyme-solubilized collagen, or neutral-solubilized collagen. In particular, atelocollagen that has been subjected to the removal treatment of the telopeptide that is the antigenic determinant of collagen at the same time as the solubilization treatment is preferred. The origin of collagen is extracted from the skin, tendon, bone, cartilage or organ of animal species such as cows, pigs, birds, fish, rabbits, sheep, mice, or humans. The type of collagen is not limited to any type that can be classified, such as type I or type III.

  The manufacturing method of the said filamentous material can be shape | molded in accordance with a conventional method. For example, it can be produced by continuous spinning from a collagen solution. At this time, the solvent of the collagen solution is not particularly limited as long as it can solubilize collagen. Typical examples include a dilute acid solution such as hydrochloric acid, acetic acid, and nitric acid, a liquid mixture of water and a hydrophilic organic solvent such as ethanol, methanol, or acetone, or water. You may use these individually or in mixture of 2 or more types in arbitrary ratios. Of these, water is most preferred. The concentration of the collagen solution is arbitrary depending on the type of collagen to be used and may be any concentration as long as spinning is possible, but is usually about 0.1 to 20% by weight, of which about 1 to 10 for wet spinning. About 5% by weight is preferable, and about 5 to 7% by weight is more preferable. Moreover, the discharge speed of the collagen at the time of spinning is arbitrary as long as it can be spun. Any device such as a general-purpose gear pump, dispenser or “various extrusion device” may be used for discharging the collagen solution during spinning. However, in order to perform uniform spinning, the collagen solution is stably generated with little pulsation. An apparatus capable of dispensing a fixed amount is preferable, and the hole diameter of the die for spinning is not particularly limited as long as spinning is possible, and can be used according to the outer diameter of the target filamentous material. The number of holes may be singular or plural, and the shape of the die is not particularly limited, and for example, a slit shape or various shapes may be used as long as spinning is possible.

  The coagulation bath used in wet spinning is not particularly limited as long as it is a solvent, suspension, emulsion or solution capable of coagulating collagen, but is not limited to inorganic salt aqueous solution, inorganic salt-containing organic solvent, alcohols. , Ketones or any combination thereof. As the inorganic salt aqueous solution, an aqueous solution such as sodium sulfate, sodium chloride, ammonium sulfate, calcium chloride or magnesium chloride, particularly an aqueous solution such as sodium chloride, sodium sulfate or ammonium sulfate is preferable. An inorganic salt-containing organic solvent in which these inorganic salts are dissolved or dispersed in alcohol or acetone may be used. In this case, an ethanol-dissolved or dispersed solution of sodium chloride is particularly preferable. Examples of alcohols include alcohols having 1 to 6 carbon atoms such as methanol, ethanol, isopropanol, amyl alcohol, pentanol or hexanol, and glycols such as ethylene glycol, preferably ethanol. Examples of ketones include acetone and methyl ethyl ketone.

  The coagulation bath is effective not only for the coagulation of collagen, but also a processing method capable of simultaneously coagulating and cross-linking collagen by combining with various cross-linking agents described later. For example, when a solution in which ethanol and glutaraldehyde are mixed is used as a coagulation bath having both a coagulation treatment and a cross-linking treatment, both steps can be performed at once, and the spun collagen yarn is subjected to a cross-linking treatment as it is. These simultaneous treatments are not only rationalized in the process, but are very effective when spinning with dilute collagen solution or spinning thin yarns.

  The collagen thread may be subjected to various known physical or chemical cross-linking treatments as necessary. The stage for performing the crosslinking treatment is not limited. That is, the non-woven fabric may be formed of a filamentous material that has been subjected to various cross-linking treatments, or may be subjected to various cross-linking treatments after the non-woven fabric is formed. Two or more kinds of crosslinking treatments may be used in combination, and the order of treatment is not limited. By this crosslinking treatment, it is possible to dramatically delay the time taken for decomposition and absorption when transplanted into a living body as compared with the case of non-crosslinking, and the physical strength is also improved. Therefore, it is possible to maintain the necessary decomposition resistance and strength in the body after the transplantation into the living body until the periodontal tissue regeneration is completed.

  Examples of physical crosslinking methods include X-ray irradiation, ultraviolet irradiation, electron beam irradiation, plasma irradiation, crosslinking treatment by thermal dehydration reaction, etc. Examples of chemical crosslinking methods include, for example, dialdehyde or polyaldehyde. Examples thereof include a reaction with aldehydes, epoxies, carbodiimides or isocyanates, tannin treatment or chromium treatment. Of these, thermal dehydration crosslinking reaction, which is one of physical crosslinking methods, is preferred.

  Furthermore, the present invention is characterized in that a coating layer of a biodegradable polymer is formed on the surface of the collagen thread. The biodegradable polymer is not particularly limited as long as it can be decomposed and absorbed in vivo, and examples thereof include polylactic acid, collagen, polyglycolic acid, polysaccharides, polypeptides or copolymers thereof. Of these, polylactic acid is preferred. What is necessary is just to use what is marketed for these biodegradable polymers, The weight average molecular weight is about 5000-2 million, Preferably it is about 100,000-300000. The biodegradable polymer coating layer has a thickness of about 0.01 to 70 μm, preferably about 0.1 to 15 μm.

  Furthermore, the periodontal tissue regeneration material of the present invention is characterized by comprising a composite filamentous material obtained by mixing a collagen filamentous material with a biodegradable polymer solution and drying it as it is. The solvent of the biodegradable polymer aqueous solution is not particularly limited as long as it is a good solvent capable of dissolving the biodegradable polymer and does not dissolve the collagen filamentous material. For example, when the biodegradable polymer is polylactic acid, halogen-based volatile organic solvents such as dichloromethane or chloroform, aromatic volatile organic solvents such as toluene or xylene, and the like are preferable. is there. On the other hand, in the case of collagen, water is suitable, but in this case, it is necessary to impart insolubility to water to the collagen filamentous material. As the method for imparting insolubility, the above-described crosslinking treatment is suitable. The concentration of these biodegradable polymer solutions is about 0.5-100 g / l, preferably about 10-50 g / l, more preferably about 15-30 g / l. In this case, the mixing ratio is about 10 to 200 ml, preferably about 20 to 80 ml, of the biodegradable polymer solution with respect to about 1 g of collagen thread. Examples of the drying method include natural drying, vacuum drying, freeze drying, vacuum freeze drying and the like, but are not particularly limited.

  When carrying out the above method, it can be easily molded into an arbitrary shape by using a molding mold. For example, as a form of periodontal tissue regeneration material, when using as a continuous porous body in which composite filaments are irregularly arranged, prepare a molding mold of the desired shape, and use collagen filaments as irregular molds Lay down so that it is arranged in The proportion of the spread is about 50 to 99.9%, preferably about 75 to 95%, when the volume of the molding mold is 100%. Next, the biodegradable polymer is uniformly poured into a mold according to the mixing ratio, and then dried. Moreover, if the said shaping | molding casting_mold | template can be shape | molded in planar membrane-like communication other antibody, since the shaping | molding planar membrane-like continuous porous body is easy to handle when adapting to a periodontium damaged part, it is preferable.

  Unlike the conventional GTR film, the periodontal tissue regeneration material of the present invention is excellent as a scaffold material for periodontal tissue regeneration because cells can adhere and grow well. Therefore, the present invention proposes a novel periodontal tissue regeneration method in which a periodontal tissue regeneration material is applied to a periodontal tissue defect portion, and a gingival flap around the periodontal tissue defect portion is covered and secured. it can. Here, adaptation means that in the conventional GTR method, a portion corresponding to a “space” in which the periodontal tissue secured by the GTR film self-regenerates is spread (dreamed). In adaptation, it is possible to perform trimming according to the shape of the affected part. The thus-applied periodontal tissue regeneration material is put over and secured by pulling the gingival flap around the periodontal tissue defect. A commercially available surgical thread may be used as the surgical thread to be sutured and fixed.

  Furthermore, the material for periodontal tissue regeneration of the present invention is a material obtained by seeding and culturing stem cells that can be induced in the periodontal tissue in the periodontal tissue regeneration material. Make it possible. Therefore, the present invention seeds stem cells on a material for periodontal tissue regeneration comprising a composite filamentous material having a collagen filamentous material and a biodegradable polymer coating layer formed on the surface of the collagen filamentous material, and cultures. The material for periodontal tissue reproduction | regeneration obtained by doing is included.

  The cell type of the cell is not particularly limited, but it is particularly preferable to use a cell constituting a tissue intended for regeneration, and various stem cells are preferably used because of their high versatility. Stem cells, epithelial stem cells, hematopoietic stem cells, vascular endothelial stem cells, neural stem cells, hepatic stem cells, inner ear stem cells, pancreatic stem cells, osteoblasts, periosteum cells, fibroblasts, embryonic stem cells or somatic stem cells, among others, mesenchymal Stem cells are preferred. In addition, any of autologous cells, allogeneic cells, and heterologous cells may be used, but autologous cells are preferred.

The stem cells are purified according to a conventional method. For example, mesenchymal stem cells derived from dogs can be purified by the following method. The iliac bone marrow (about 10 ml) is collected under general anesthesia from any dog of about 15-25 kg and the bone marrow is placed in a syringe filled with about 5-20 ml of about 5000-10000 units of heparin to prevent blood clotting. Aspirate and mix in medium such as DMEM. As an additive to this medium, 10% fetal bovine serum (FBS), penicillin G (concentration of about 75 to 125 U / ml), streptomycin (concentration of about 75 to 125 μg / ml) or amphotericin B (concentration of about 0.10 to 0.10) Antibiotics such as 0.50 μg / ml). The mesenchymal stem cells are concentrated from the nucleated cell fraction of the bone marrow by density gradient centrifugation using 1.063 g / cc of Percoll buffer. Nucleated cells in about 5 ml of medium are carefully layered on about 10-30 ml of Percoll reagent and centrifuged. Centrifugation is performed at 300-500 g for about 20 minutes. After collecting and washing the cells at the medium-Percoll reagent interface, the culture dish is seeded with about 5 to 10 ml of the above medium at a cell concentration of about 1.0 to 2.0 × 10 ⁴ cells / cm ² . The cells obtained by the above method are cultured at 37 ° C. in a humidified atmosphere in the presence of 5% CO ₂ . On the second day of culture, non-adherent cells not attached to the culture vessel were removed together with the culture medium. During the culture, the medium was exchanged twice a week, and 0 to about 10 to 13 days of culture. The cells are detached from the culture vessel and recovered by exposure to an EDTA solution containing 0.05% trypsin (concentration of about 0.25 to 0.75 mM) for about 5 minutes. Subsequent subculture is performed by re-seeding at a concentration of about 1.0 × 10 ^{3 to} 2.0 × 10 ³ cells / cm ² , and cells approaching confluence, typically after seeding. Cells after 5-7 days are collected.

In the method of culturing hepatocytes purified by the above method, stem cells are seeded on the periodontal tissue regeneration material prepared by the above method or the like on a cell culturing vessel. Examples of the container for culturing cells include petri dishes, flasks, bags, and the like, but are not limited thereto. Examples of the seeding method include a method in which a medium in which cells are suspended is directly applied to a periodontal tissue regeneration material. The amount of cells in the suspension is about 0.1 × 10 ^{3 to} 2.0 × 10 ⁶ cells / 100 μl, preferably about 0.1 × 10 ^{4 to} 2.0 × 10 ⁵ cells in terms of cell density. / 100 μl. As a medium used for these cell suspensions, it is preferable to use an appropriate medium according to the purpose such as cells to be cultured and differentiation / proliferation, and examples thereof include αMEM medium, DME medium, and DMEM medium. The cells in the droplets thus dropped on the cell support are incubated for about 0.5 to 5 hours at about 37 ° C., 100% humidity and 5% by volume carbon dioxide gas until they adhere on the cell support. To do. The seeded stem cells are cultured by conventional means. For example, it can be cultured at room temperature of about 37 ° C. in a humidified atmosphere in the presence of 5% CO ₂ . The number of days for culturing is usually about 7 to 30 days.

  Even when the periodontal tissue regeneration material is obtained through the above-described hepatocyte culture step, it can be used in the novel periodontal tissue regeneration method. The reproduction method can be carried out in the same manner as described above, and is not particularly limited.

  Further, when the periodontal tissue regeneration material of the present invention is a planar membrane-shaped continuous porous body having a thickness of about 0.05 to 2 mm, preferably about 0.1 to 1 mm, it is used as a blocking film in the conventional GTR method. can do. A gap is created surgically between the gums and roots for the regeneration of the desired periodontal tissue, causing a healing reaction in the form of a new attachment, while the gaps are capped with a blocking membrane, and the gingival epithelium This is a method of inhibiting the invasion, that is, the downgrowth. Regeneration of periodontal tissue can be promoted by securing a space for regeneration of periodontal tissue while preventing downgrowth of the gingival epithelium using a blocking film.

  The material for periodontal tissue regeneration of the present invention may be selected in a form that can be created by the user's hand in view of the usefulness of being able to be molded into a shape suitable for the shape of the affected area. Therefore, in order to prepare the periodontal tissue regeneration material by the user's hand, it includes a kit form comprising a collagen thread and a biodegradable polymer aqueous solution. In some cases, a mold may be included.

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

Example 1: Manufacture of collagen thread The collagen aqueous solution was discharged from a nozzle attached to the syringe by applying air pressure to a syringe filled with a 7 wt% collagen aqueous solution. The discharged 7% by weight collagen aqueous solution was immediately dehydrated and solidified into a filament shape in an ethanol tank containing 3L of 99.5% by volume ethanol. The filamentous collagen pulled up from the ethanol bath was rotated with a roll-shaped winder having a diameter of 100 mm and a total length of 200 mm, and wound while being dried with dry air. During winding, the roll-shaped winder was reciprocated in the axial direction at a speed of 1.5 mm / s. After completion of winding, the collagen filamentous material is removed from the roll-shaped winder, and thermal dehydration cross-linking treatment is performed at 135 ° C. under reduced pressure (1 Torr or less) for 24 hours using a vacuum dry oven (manufactured by EYELA: VOS-300VD type). To obtain a collagen thread (outer diameter of about 10 to 15 μm) subjected to thermal crosslinking treatment.
Next, the collagen filaments that had been subjected to the thermal crosslinking treatment were immersed in a 7.5 wt% aqueous sodium hydrogen carbonate solution for about 5 minutes for neutralization treatment, and then immediately washed with a sufficient amount of 70 vol% ethanol. Subsequently, it was immersed in a sufficient amount of 99.5% by volume ethanol, allowed to dry naturally, and subjected to a thermal dehydration cross-linking reaction treatment at 135 ° C. under reduced pressure (1 Torr or less) for 24 hours using the vacuum dry oven described above.

Example 2: Preparation of periodontal tissue regeneration material About 0.02 g of collagen filamentous material obtained in Example 1 was formed with a gap of about 0.6 cm ³ (bottom area of about 1.5 cm ² , thickness of about 0.4 cm). A polylactic acid (molecular weight: 100,000) dichloromethane solution prepared to a concentration of 0.15 g / l was poured into a mold (female). The ratio at this time was about 40 ml of polylactic acid methylene chloride solution with respect to about 1 g of collagen filamentous material. After capping with a mold (male mold) and mixing uniformly, methylene chloride was naturally dried to prepare a periodontal tissue regeneration material.

Example 3 Mesenchymal Stem Cell Culture Mesenchymal stem cells were collected from canine iliac bone marrow and cultured in MSCB medium (BIO WHITKERKER, CA, USA) for 1 week. Next, the mesenchymal stem cells were cultured for one week in an MSCB medium supplemented with ascorbic acid, dexamethasone, and β-glycerophosphate, and then seeded on the periodontal tissue regeneration-inducing substrate prepared in Example 2 and further cultured for one week. Thus, a periodontal tissue regeneration material in which mesenchymal cells were cultured was obtained.

Experimental Example 1: Animal Implantation Experiment The periodontal tissue around the 3rd mandibular premolar and the 4th mandibular premolar in the dog from which the mesenchymal stem cells were collected in Example 3 was removed to create a horizontal bone defect. . The gingival flap was restored and left for 3 months to be exposed to oral bacteria. Thereafter, the gingival flap was opened again to remove the infected periodontal tissue, and the root bifurcation was completely exposed (FIG. 1).
Next, the periodontal tissue regeneration substrate obtained by culturing mesenchymal cells obtained in Example 3 was adapted (dreaming) according to the shape of the implant site (FIG. 2), and the periodontal tissue was removed. The implant was transplanted around the root of the tooth, and a gingival flap was placed around the implant and fixed by suture (FIG. 3).

  As a result of visual observation and X-ray photography after 4 months, the alveolar crest height was clearly raised by the newly formed bone, and good bone formation was confirmed. In addition, as a result of excision and histological evaluation 6 months after the operation, there were signs of periodontal tissue regeneration such as periodontal ligament and cementum between the root surface and the alveolar bone (FIGS. 4 and 5). .

Comparative Example 1: Control Example of Animal Experiment For a dog different from Experimental Example 1, periodontal tissues around the 3rd mandibular premolar and the 4th mandibular premolar were removed to create a horizontal bone defect. The gingival flap was restored and left for 3 months to be exposed to oral bacteria. Thereafter, the gingival flap was opened again to remove the infected periodontal tissue, and the root bifurcation was completely exposed.

  As a result of visual observation and X-ray imaging after 4 months, in Comparative Example 1, bone regeneration was observed only at the base of the defect, and the alveolar crest height remained low, clearly showing bone formation as compared to Experimental Example 1. Was inferior (FIGS. 6 and 7). In addition, as a result of excision at 6 months after the operation and histological evaluation, no signs of periodontal tissue regeneration such as periodontal ligament and cementum were observed.

  The periodontal tissue regeneration material of the present invention is a good scaffold material for periodontal tissue regeneration, and can be applied to severe periodontal tissue damage that had to be abandoned in conventional clinical settings. It has regenerative ability and is very excellent in decomposition and absorption. Further, the periodontal tissue regeneration material can be used as a blocking film (GTR film) that has been used in the conventional GTR method, and is extremely excellent in strength.

It is a photograph of the 3rd mandibular premolar and the 4th mandibular premolar of the dog which exposed the root bifurcation part completely. It is the photograph which applied (dreaming) the periodontal tissue regeneration material obtained in Example 3 to the 3rd mandibular premolar of the dog and the 4th mandibular premolar of the dog which exposed the root bifurcation part completely. After applying the material for periodontal tissue regeneration obtained in Example 3 to the dog's 3rd mandibular premolar and 4th mandibular premolar whose dog roots were completely exposed, the surrounding gingival flap was It is a photograph that is put on and secured by stitching. It is a photograph 4 months after transplantation in Experimental Example 1. 4 is a photograph of X-ray photography taken 4 months after transplantation in Experimental Example 1. 4 is a photograph of Comparative Example 1 4 months after transplantation. 3 is an X-ray photograph of Comparative Example 1 4 months after transplantation.

Claims (9)

  A scaffold material for periodontal tissue regeneration, which is a continuous porous body molded from a composite thread having a collagen thread and a biodegradable polymer coating layer.   The scaffold material for periodontal tissue regeneration according to claim 1, wherein the continuous porous body is a film having a thickness of 0.05 to 70 mm.   The scaffold material for periodontal tissue regeneration according to claim 1, wherein the collagen filamentous material has an outer diameter of 5 to 70 µm.   The scaffold material for periodontal tissue regeneration according to claim 1, wherein the biodegradable polymer is polylactic acid, collagen, polyglycolic acid, polysaccharide, biodegradable polyester or polypeptide.   The scaffold material for periodontal tissue regeneration according to claim 1, wherein the biodegradable polymer is polylactic acid.   Cells are seeded on a periodontal tissue regeneration material, which is a continuous porous body formed by a composite thread having a collagen thread and a biodegradable polymer coating layer formed on the surface of the collagen thread. A scaffold material for periodontal tissue regeneration obtained by culturing.   The cells are mesenchymal stem cells, epithelial stem cells, hematopoietic stem cells, vascular endothelial stem cells, neural stem cells, hepatic stem cells, inner ear stem cells, pancreatic stem cells, osteoblasts, periosteum-derived cells, fibroblasts, embryonic stem cells or somatic stem cells A scaffold material for periodontal tissue regeneration according to claim 6. A method for producing a scaffold material for periodontal tissue regeneration, comprising mixing a collagen thread and a biodegradable polymer solution, followed by drying to form a continuous porous body. Production of scaffold material for periodontal tissue regeneration, characterized by seeding and culturing cells in a continuous porous body formed of a composite filamentous material having a collagen filamentous material and a biodegradable polymer coating layer Method.

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