FI78825C - FOEREMAOL FOER BEHANDLING AV PERIODONTAL SJUKDOM. - Google Patents

Description

78825

Product for the treatment of periodontal disease

The present invention relates to a product for the treatment of periodontal disease, in particular a product for preventing the formation of a periodontal pocket and for curing periodontal defects.

Periodontal disease is a disease of the periodontium (the root membrane of the tooth), the tissue that covers and supports the tooth. As shown in Figure 1 of the drawing, these tissues include: gingival 1, soft gingival tissue of the mouth, gingival epithelium 2, a gingival protective surface layer that closes against the tooth at the point where the tooth enters the oral cavity, dental cement (not shown) that is a natural adhesive covering the root, the alveolar bone 3, wherein the jaw bone surrounds the root of the tooth and the periodontal ligament 4, the connective tissue that secures the tooth and supports it between the alveolar bone and the root of the tooth.

The gingival tissue surrounding a healthy adult tooth forms a furrow 5, i.e., a score line at the point where it attaches to the tooth. In the early stages of periodontal disease, the bacteria break the attachment of the gingival epithelium to the tooth and force the epithelium to adhere again apically (toward the root) away from the infected tissue. Because the tissue is prone to disease, new attachment is weak. The additional infection increasingly displaces the attachment apically until the tooth is surrounded by a loose sleeve of diseased gingiva that forms a pocket that is much deeper than a normal spleen. The loose sleeve, called the periodontal pocket 6, is difficult to clean because the toothbrush and floss cannot reach the bacteria and plaque that accumulate in the pocket. As the disease expands the periodontal pocket, the dental cementum, periodontal ligament, and alveolar sciatic bone rupture, leaving a periodontal injury filled with 2,78825 plaques and bacteria. The loss of a sturdy periodontum eventually leads to tooth loss.

Periodontal disease is the most common disease known to humans, reportedly affecting 75% of adults, and is the leading cause of tooth loss after the age of 35 years. 55 million teeth are lost to the disease each year in the United States.

Conventional treatment of periodontal defects involves attempts to surgically alter the morphology of the periodontal pocket or to achieve coronal, i.e., tooth-toward, tooth attachment to the tooth.

Previous attempts to correct periodontal defects with synthetic materials have not resulted in the attachment of gin-givial tissue to the tooth while controlling the apical movement of the epithelium, i.e., migration. For this reason, these techniques are only of limited success. It is an object of the present invention to provide a means by which periodontal disease could be treated by arresting the migration of epithelium close to its pre-disease level. In terms of gingival attachment, apical injury, can then be cured with appropriate periodontal tissues.

U.S. Patent No. 4,007,494 discloses the use of a porous, biocompatible material as a bone patch to cover the bare end of a broken bone and to allow ingrowth of bone and other tissue, wherein the patch contains a biologically acceptable, non-porous material. However, the publication makes no mention of the treatment of periodontal disease, nor does it disclose any product suitable for this use.

According to the present invention, there is provided a product for the treatment of periodontal disease, wherein the treatment is based on promoting the growth of gingival tissue into the product around a desired groove line. The product comprises a piece of porous material capable of supporting the ingrowth of gingival-connective tissue and preventing apical migration of gingival epithelium with a biologically compatible non-porous support on one side of the piece that can be wrapped at least partially around the tooth surface.

As a result of the porous material being located between the gingival tissue and the tooth, the porous material fills with gingival connective tissue and thus stops the apical downward growth of the gingival epithelium. As such, the area that previously comprised the periodontal pocket is filled with healthy periodontal tissue.

The present invention can be used in a method of treating periodontal disease, comprising: a) temporarily separating gingival tissue from a tooth surface in an area where periodontal disease occurs, b) partially overlapping a product with a tooth surface perimeter, the product comprising a piece of porous material capable of supporting gingival connective tissue ingrowth and prevent apical migration of the gingival epithelium with a biocompatible, non-porous support on one side of the piece that can be wrapped at least partially around the tooth surface; and c) repositioning the gingival tissue around the tooth and in contact with the product; the product is placed between the gingival tissue to be reattached and the tooth.

The accompanying drawings illustrate by way of example three embodiments of the invention.

Figure 1 shows a mesial-distal (parallel to the jawbone brush) cross-sectional view of a healthy adult tooth and periodontium.

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Figure 2 shows a close-up of the gingival recess of Figure 1.

Figure 3 shows a mesial-distal cross-sectional view of a periodontally diseased tooth with a periodontal pocket and defect.

Figure 4 shows a mesial-distal cross-sectional view of the diseased tooth of Figure 3 corrected using the present invention.

Figure 5 is a three-dimensional view of uniaxial expanded polytetrafluoroethylene.

Figure 6 is a three-dimensional view of a first preferred embodiment of a product according to the invention.

Figure 7 is a three-dimensional view of another preferred embodiment of a product according to the invention.

Figure 8 is a three-dimensional view of a third preferred embodiment of a product according to the invention.

Preferably, a periodontally diseased tooth is prepared for repair by exposing all diseased parts of the tooth and periodontal. For example, one or more strips of yoke 1 buccal (facing the cheek) or lingual 5 78825 (facing the tongue) may be turned away from the root of the tooth and the surrounding bone. The exposed defect can then be cleaned by conventional periodontal techniques, such as scaling or scraping. Topical antibiotics can be used on diseased sites to keep bacterial colonies away.

A strip of porous material (described in detail below) is placed against the surface of the tooth and should extend coronally to the plane where the defect is to be corrected. The porous material is placed in a plane on the tooth just apically at the point where the gingival epithelium (fissure) is to end.

The porous material can be wrapped around the entire circumference of the tooth. It is preferably placed around the part of the tooth ring from which periodontal tissue attachment has been lost due to disease. The porous material can be placed evenly against the tooth surface. Preferably, the porous material extends outwardly from the tooth surface to cover the bone defects surrounding the tooth.

The porous material should be tightly attached to the tooth surface so that the gingival epithelium cannot enter between the porous material and the tooth surface. The porous material can be placed simply between the gingival: tissue and the tooth surface, or it can be attached to the tooth surface.

The porous material can be attached to the tooth surface by gluing the material to the tooth with suitable dental adhesives. A suitable dental adhesive is non-toxic to the surrounding tissues, is able to form an adhesive bond in the open oral environment, remains long enough to allow the defect to be corrected, and is capable of forming a bond between the porous surface and the tooth surface. Tooth adhesives are e.g. zinc euginol, zinc phosphate, zinc silicophosphate, acrylic, glass ionomer silicate and polycarboxylate binders.

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The porous material can also be attached to the area around the tooth using sutures or strands. Sutures can be used to bind the porous material to the surrounding tissue and then hold it tightly against the tooth. The suture material can also be used to join the ends of the porous material together to secure the porous material around the tooth. The wire-like material can be attached to the ends of the porous material and used to bind the porous material around the tooth. Suitable suture or thread-like materials must be biologically compatible, i. they must be of materials which do not adversely affect the oral tissue. In addition, sutures or thread-like materials must not act as a channel for bacterial infiltration and must not be resorbed until such a long time has elapsed that the periodontal tissue has filled the damaged area.

The gingival tissue is placed against the porous material so that the porous material separates some part of the gingival from the tooth surface. The coronal portion of the porous material may extend coronal to the gingival tissue. Preferably, as shown in Figure 4, the porous material 8 is completely coated with gingival tissue, whereby no part of the porous material remains exposed with respect to the oral cavity.

; The porous material may remain in the mouth for the rest of the patient's life.

Alternatively, the porous material may be removed after a sufficient period of time until the periodontal tissue fills the defect and adheres to the tooth surface.

The porous material should be made of biologically compatible materials. Preferably, the porous material is soft and flexible so that it conforms to the curvature of the tooth and surrounds the bone and does not cause tissue necrosis in the tissues against which it is placed. Suitable biologically suitable materials that can be made porous include e.g. silicones, polyurethanes, polyethylenes * polysulfones, polyacrylics, 7,78825 polycarboxylates, polyesters, polypropylenes, poly (hydroxyethyl methacrylates) and polyfluorinated polymers such as fluorinated ethylene propylene and polytetrafluoroethylene.

The above can be made porous by methods known in the art which keep the materials such that they are able to support gingival connective tissue ingrowth while preventing apical migration of the gingival epithelium. Such methods include e.g. careful sintering of controlled size beads, combining materials with a partially absorbable graft that absorbs or could be absorbed in vivo or in vitro to form a porous surface, weaving or knitting fibers together to form a tissue-like material, or using a blowing agent during treatment to create bubbles and produce pores as it hardens.

In a preferred embodiment, the porous material is expanded polytetrafluoroethylene (expanded PTFE). Expanded PTFE is a highly inert and biocompatible material used in medical implants. U.S. Patents 3,953,566 and 4,187,390 disclose methods for making expanded PTFE and explain its porous structure. The porous structure of the expanded PTFE is shown in more detail in Figure 5. The microstructure of the expanded PTFE is a three-dimensional matrix of nodes 9 interconnected by fibrils 10.

The pore size of the expanded PTFE can be characterized by determining the bubble point and average flow pressure of the material. The bubble point and mean flow pressure are measured according to American Society for Testing and Materials Standard F316-80 using ethanol.

The density of expanded PTFE determines the number of voids in the material into which connective tissues can grow. The density of expanded PTFE is the ratio of the mass of a given sample of expanded PTFE to its volume.

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The fibril length of expanded PTFE is determined here as the average of ten measurements between nodes connected by fibrils in the direction of expansion. Although Figure 5 shows a material that is expanded in only one direction, PTFE that is expanded in more than one direction may equally well be used in the invention. To measure the average fibril length of the expanded PTFE, two parallel lines are drawn across the photomicrograph of the surface of the material about 40-50 times magnified to divide the micrograph into three equal areas. If the material is uniaxially expanded, these lines are drawn in the direction of expansion (i.e., in the direction of fibril orientation). By measuring from left to right, five measurements of fibril length are made along the top line of the photomicrograph, starting from the first node to intersect the line near the left edge of the photomicrograph and continuing with successive nodes intersecting the line. Another five measurements are made along the second line from right to left, starting from the first line to cut the line on the right in the photomicrograph. If the material is expanded in more than one direction, the lines are drawn and the fiber lengths are measured as described above except when the knot is not connected to the intersection of the line drawn by the fibrils. In this case, the fibril length from node to node that provides the smallest angle with the draw line is measured along the axial orientation of the fibril. The ten measurements obtained by this method are averaged to form the average fibril length of the material.

Materials with average fibril lengths greater than 60 microns (i.e., pn), preferably greater than 100 microns, with ethanol bubble points less than 2.0 psi (13.8 kPa), preferably less than 0.75 psi (5.2 kPa), with an average ethanol flow pressure of less than 10 psi (69 kPa), preferably less than 3.0 psi (21 kPa), and densities of less than 1 g / cm 3 and preferably 0.3 to 0.1 g / cm 3, improve connective tissue ingrowth; and therefore, they are preferably used in the present invention.

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When expanded PTFE is used as the porous material, it is most convenient that a portion of the nodes 9 pass through the wall thickness of the expanded PTFE, as shown in Figure 5, to form channels for tissue ingrowth and to produce a fracture-resistant wall. Expanded PTFE, in which the nodes do not pass through its wall thickness, breaks more easily due to biting forces, resulting in a decrease in pore size, an increase in density, and difficulty in ingrowth. Preferably, most of the nodes run across the wall thickness dimension. In the preferred embodiments, an expanded gingival interface with PTFE with a wall thickness of about 1 mm is used.

The shape of the expanded PTFE may vary. Figure 6 shows the "Apron" shape. The collar 11 of the apron is pulled tightly against the circumference of the tooth, preferably by tying the ends 12 of the collar together with a pair of wires 16 attached to the ends 12 of the cladding collar. The lower part 13 of the apron is placed coronally on the bone defects adjacent to the tooth. Figure 7 shows a "collar shape". The collar of expanded PTFE is pushed tightly against the circumference of the tooth, preferably by tying the ends 14 of the collar together using wires (not shown). Figure 8 shows another preferred "location" format. The notch 15 of the site, shown in Figure 8, is positioned tightly against the tooth, preferably using suture material to bond the sides of the notch to the tissue surrounding the tooth.

The porous material can be treated or filled with biologically active agents such as antibiotics, fibrin, thrombin and collagen. These agents can improve connective tissue formation in the porous material and prevent infection during healing.

The porous material is supported by a non-porous material on the side 17 of the porous material which: is placed on the tooth surface. The non-porous material helps maintain the open, porous structure of the porous material. The non-porous material also helps to close the porous material against the tooth surface by adapting to surface irregularities. Suitable non-porous materials include e.g. chemical substances listed above and combinations thereof.

The non-porous material can also be used to adhere the porous material to the tooth surface, whereby it acts as a surface that binds to the adhesive adhering to the tooth. In this embodiment, a suitable dental adhesive, as described above, may be applied to the tooth or to the non-porous side of the porous material prior to gluing the material to the tooth. In another embodiment, one component of the multicomponent adhesive may be incorporated into the non-porous material. The adhesive or the remaining components of the adhesive are added immediately before the material is glued to the tooth.

The porous material may be formed as a collar, a seat, or an apron as shown in the above embodiment. Preferably, the porous material is formed into an apron in which the yarns act as "apron strips", as shown in Figure 6.

Preferably, the porous material is expanded PTFE.

The wires may be attached to the piece of porous material by any method that provides an attachment capable of holding the porous material in place until sufficient ingrowth of periodontal tissue has occurred. Preferably, the yarns are knotted or knitted into a porous material. If both the porous material and the wires consist of expanded PTFE, the two can be joined by pressure and heat.

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The products of the present invention are preferably sterilized before being placed in a periodontal pocket. These products are preferably sterilized and placed in a package with a sterile inner environment.

The production of porous polytetrafluoroethylene and the planting of the products formed therefrom are described in more detail below.

Manufacture of porous PTFE material

Expanded PTFE was prepared according to U.S. Patents 4,187,390 and 3,953,566 as follows: A mixture of PTFE resin in a liquid lubricant was extruded into a tubular shape. The extruded tubular form was dried for 96 hours at about 300 ° C, which removed the lubricant. The tubular shape, kept at a temperature of about 195eC, was then stretched at a constant speed along the central axis of the tube at about 75% / sec until it was almost 10 times its original length, the speed being determined as follows: ϋ x 100% li (t) where lf * final length, li = initial length and t = total expansion time. After stretching, the tube was longitudinally fixed and heat treated at about 375 ° C for about 75 seconds. The expanded PTFE tube was then split lengthwise through its wall and laid flat. The wall was about 1 mm thick and knots passed through its wall thickness. The material had an ethanol bubble point of about 0.5 psi (3.4 kPa) and an average ethanol flow pressure of about 1.0 psi (6.9 kPa). The average fibril length was about 200 microns and the density was about 0.2 g / cm 3.

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Planting of apron-shaped PTFE claddings

Expanded PTFE linings corresponding to those shown in Figure 6 were implanted in dogs.

The badge portion and collar portion of the apron were cut from the expanded PTFE so that the collar was about 2 cm long and 2 mm wide and the badge portion extended about a centimeter from the collar. 6-0 GORE-TEX (trademark) Expanded PTFE Suture yarn manufactured by W.L. Gore & Associates, Flagstaff, Arizona, was passed through each end of the apron collar. The whole apron was assembled in a clean environment. The apron was sterilized before implantation.

At implantation, the buccal and lingual bone membrane strips were inverted around the canine interdental tooth. Approximately 2 mm of bristle bone was removed from the perimeter of the tooth to expose the root surface against which the aprons could be fitted. Either a three-walled mid-injury or a single-walled cheek-side injury was induced adjacent to the tooth using a drill and chisels. The collar of the apron was placed around the circumference of the tooth, whereby the breast was placed on top of the corona-induced bone defect. GORE-TEX (trademark) The ends of the Expanded PTFE sutures were then tied together on the tooth on the side opposite the injury, pulling the ends of the collar together and tightening the Apron around the tooth. Any excess suture was cut off and the gingival strips were again placed on the apron by suturing them in place. A total of five grafts were placed in two dogs.

One week after surgery, the transplant sites were evaluated clinically. After initial healing, the inspection showed in all cases a healthy-looking gingiva attached to the apron and forming a 2-3 mm deep normal-looking furrow. In one case, a small portion of the apron had been carelessly exposed to the oral cavity, but the entire is 78825 surrounding tissue appeared healthy and had fitted to the remainder of the apron.

Two grafts, including the above case, were dissected on days 20 and 30 and examined histologically. The collar and the downward portion of the expanded PTFE appeared to be filled with connective tissue in all areas except the area exposed to the oral cavity.

The epithelium clearly stopped its apical migration in or directly coronal to the swollen PTPEs and the new bone had filled in the defects formed.

Planting of piece-shaped products

The expanded PTPE was cut into small pieces measuring approximately 12 mm x 12 mm as shown in Figure 8. The pieces had an ethanol bubble point of less than 0.75 psi (5.2 kPa), an average ethanol flow pressure of less than 3 psi (21 kPa), an average fibril length greater than 100 microns, density 0.3 ... 0.1 g / cm3 and wall thickness about 1 mm. After the gingival strips were inverted, triangular mesial defects were formed in the roots of the first two molars of the dog and the fourth premolar of the lower jaw of the second dog. The pieces were fitted over the bone defects and fitted to the bone ridge so that the root of the tooth to be treated was in the hole of the piece. The gingival ramps were repositioned on the pieces and sutured in place. Molar grafts were removed on days 19 and 20 after surgery, and the premolar graft was removed 30 days after surgery.

At all sites, approximately 2 mm of expanded PTFE remained exposed with respect to the oral cavity adjacent to the mesial side of the treated teeth. Histological analysis showed that the gingival tissue had filled the space between the piece cavity and the tooth. The new bone had filled in the defects and the pieces had clearly I4 78825 prevented the growth of gingival tissue into the defective condition. Parts of the expanded PTFE that were not exposed to the oral cavity were healed with healthy, vascularized connective tissue. The epithelium had clearly stopped apical migration from expanded PTFE at the interface between exposed and healed portions.

This method of treatment was a bit unfortunate because the gingival tissue was able to grow between the surfaces of the piece and the tooth. It may be possible to attach the notch of such a piece more tightly to the tooth by tying the piece to an adjacent tooth with braces or other suitable means. Such a piece may allow the formation of a normal fissure around the tooth without the formation of gingival tissue between the piece and the tooth or without exposing the piece to the oral cavity. The bone defect can be filled with suitable periodontal tissues as shown in the example.

The following examples illustrate the present invention.

Example 1

The expanded PTFE collars shown in Figure 7, supported by medical silicone and polyurethane, were implanted in dogs. Medical silicone, marketed by Dow-Corning Corporation, and polyurethane, Cardiomat 610 (trademark), marketed by Kontron Cardiovascular Inc., were fitted to expanded PTFE as a thin support and allowed to cure. The expanded PTFE had an ethanol bubble point of less than about 0.75 psi (5.2 kPa), an average ethanol flow pressure of less than about 3 psi (21 kPa), an average fibril length greater than about 100 microns-a, and a density of about 0.3 - 0.1 g / cm 3 and a wall thickness of about 1 mm.

The supported, expanded PTFE was cut into strips (collars) about 2 mm wide and 2 cm long. collar

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is 78825 sets were sterilized and implanted in premolar sites according to the method described in the example without producing defects. The side of the collars supported with slicone or polyurethane was placed against the tooth, and each collar was fastened around the tooth by tying its ends together with GORE-TEX (trademark) Expanded PTFE sutures. Four grafts were taken between days 19 and 32 postoperatively for histological analysis.

Inspection of the grafts prior to removal showed a normal-looking furrow with no inflammation and gingiva attached to the collar. Microscopic examination of the graft showed that the polyurethane and silicone supports were attached to the tooth root in most places. The expanded PTFE was filled with connective tissue and the gingival epithelium was attached to the connective tissue in the collar, clearly stopping its apical migration.

Example 2

The expanded PTFE with urethane support was glued to the dog's teeth using a conventional glass ionomer tooth adhesive. The ethanol bubble point of the expanded PTFE was less than 0.75 psi (5.2 kPa), and the average ethanol flow pressure was less than 3 psi (21 kPa), the average fibril length was greater than 100 microns, and the density was 0.3 to 0, 1 g / cm 3, and the wall thickness was about 1 mm. It was supported by a glass ionomer mixture, Chembond (trademark) Glass Ionomer Cement, marketed by L.D. Caulk Company, and a mixture of liquid urethane, Cardiomat 610 (trademark) Polymer. About 1.2 cm 3 of urethane was mixed with about 1 g of powder and sprayed as a thin coating on one side of the expanded PTFE. The support was allowed to cure for about 24 hours. The supported, expanded PTFE was sterilized.

A small piece of supported material, approximately 1 cm x 0.5 cm, was glued to the root of the dog's right maxillary canine. After the gingival ramp was inverted, the glass ionomer adhesive was mixed according to the manufacturer's instructions and placed on top of the root. The supported side of the expanded PTFE was pressed into the cement before the cement had hardened and the excess cement was removed. After the adhesive had cured, the gingival ramp was repositioned on the expanded PTFE and sutured in place.

About a month after surgery, the graft was removed. Microscopic examination showed that the support had not remained fully attached to the tooth, but the expanded PTFE had been filled with healthy, vascularized connective tissue. The gingival epithelium appeared to be attached to connective tissue and clearly arrested epithelial apical migration.

Example 3

The Apron as shown in Figure 6 and the two collars shown in Example 1 were supported by a thin strip of either silicone or urethane elastomer. Approximately 0.5 mm wide strips of Cardiomat 610 (trademark) Urethane or Dow Corning medical silicone were forced over the length of the collar by hand syringe expanded PTFE. The strips were placed on the side of the collar that was meant to fit against the tooth. The collar of expanded PTFE was kept loose for about 75% of its fully stretched length during elastomer application, so that after the collar was stretched around the tooth and the ends of the collar were tied together with sutures, the elastomer held the collar against the tooth as the elastic waistband holds the pants. against the waist.

Each graft was sterilized and implanted in the premolar sites of the dog, with the downward portion of the apron covering the defect as shown in Example 1 and the collars placed in the defect-free locations. In all cases, after about a week of initial healing, examination of n 78825 showed healthy-looking gingiva that had adhered to the expanded PTFE and formed a normal-looking furrow adjacent to the tooth. Histological analysis showed that the epithelium clearly stopped its apical migration in or directly coronally with expanded PTFE filled with connective tissue. The new bone had healed apically apically to the apron.

Example 4

The expanded PTFE was glued to the tooth using an acrylic cement. The ethanol bubble point of the expanded PTFE was less than 0.75 psi (5.2 kPa), and the average ethanol flow pressure was less than 3 psi (21 kPa), the average fibril length was greater than 100 microns, and the density was 0.3 to 0, 1 g / cm 3 and the wall thickness was about 1 mm. Concise (trademark) and Silar (trademark) cements supplied by Dental Products / 3M were used.

After the buccal gingival strips were inverted from the canine maxillary canine, the exposed root was notched about 0.5 mm deep and 2 mm wide directly from the bone surrounding the root from the mesial side to the distal side of the exposed tooth.

Silar (trademark) paste, mixed according to the manufacturer's instructions, was then used to cover the notch.

A strip of expanded PTFE that had been sterilized was cut about 2 mm wide and long, sufficient to pass from the mesial side to the distal side of the exposed root. Concise (trademark) resin liquids were mixed with Concise (trademark) paste components to obtain a paste that could be sprayed and attached to one side of a strip of expanded PTFE. The paste side of a strip of expanded PTFE was placed against a house on top of the root filled with Silar (trademark) 78825. The adhesive was allowed to cure and the gingival ramp was repositioned on a strip of expanded PTFE and sutured in place.

After 40 days, the graft was removed. The strip of expanded PTFE appeared to be well attached to the tooth. The epithelium appeared to terminate against the expanded PTFE, but the gingival tissue surrounding and in the expanded PTFE showed a clear adverse reaction to the adhesive.

An adhesive system that could bind a strip of expanded PTFE to the tooth and that would be biologically compatible with the oral tissue would be a more useful treatment.

Claims (6)

78825 A product for the treatment of periodontal disease, characterized in that it comprises a piece of porous material (11) capable of supporting the ingrowth of gingival connective tissue and preventing apical migration of the gingival epithelium with a biocompatible, non-porous support on one side of the piece (11). 17), which can be wrapped at least partially around the tooth surface. Product according to Claim 1, characterized in that the non-porous support (17) is made of polyurethane. Product according to Claim 1, characterized in that the non-porous support (17) is made of silicone. Product according to claim 1, characterized in that it has at least one filament (16) attached to each opposite end (12) of the piece (11) to ensure that the material adheres to the tooth. Product according to one of the preceding claims, characterized in that it is in the form of an apron. Product according to one of the preceding claims, characterized in that it contains a biologically active substance.