Bone regeneration using the principie of guided tissue regeneration

Sture Nyman Department of Periodontology, University of Gothenburg, Gothenburg, Sweden and University of Berne, School of Dental Medicine, Berne Switzerland

. Nyman S: Bone regeneration using the prineiple of guided tissue regeneration. J Clin Periodontol 1991; 18: 494-498. Abstract. The biological principle of "guided tissue regeneration" (GTR) was developed for regenerating periodontal tissues, lost as a result of periodontal disease. This principle was based on the hypothesis that non-desirable types of tissue cells can be prevented from migrating into a wound by means of a membrane barrier and at the same time giving preference to those particular cells to repopulate the wound, which have the capacity to regenerate the desired type of tissue. This principle may have its application in many areas of surgery, aimed at regeneration of lost tissues. One such area is osseous surgery aimed at bone regeneration. In the present paper, a series of experiments in laboratory animals using the method of GTR for regeneration of various types of bone defects are presented as well as examples of application in humans for regeneration of jaw bone defects in conjunction with the placement of dental implants.

In the last decade, numerous animal studies have documented the possibility of excluding non-desirable tissue cells from repopulating a wound area by means of membrane barriers and by favoring the proliferation of defined tissue cells in order to obtain wound healing with a desired type of tissue. This principle was developed for regenerating periodontal tissues lost as a result of inflammatory periodontal disease (for review, see Nyman et al. (1989)). New connective tissue fiber attachment and new cementum formation were promoted by excluding dentogingival epithelium and gingival connective tissue proliferation into the wound area adjacent to the root surface and, simultaneously, creating a space to give preference to periodontal ligament cells for coronal migration. This new approach for reconstructive periodontal therapy was termed "guided tissue regeneration" and was tested in several human studies for a variety of periodontal defects (Nyman et al. 1982, Gottlow et al. 1986, Pontoriero et al. 1988, 1989, Becker et al. 1988, Schallhorn & McClain 1988). In the following section, a series of experiments are briefly presented, studying the possible application of the guided tissue regeneration principle on bone regeneration more in general and not related to the treatment of a periodontal defect.

Experiments

In a first study by Dahhn et al. (1988), standardized through-and-through osseous defects were prepared in the angular region of the mandible on both sides of the jaw in 30 Sprague-Dawley rats following elevation of mucoperiosteal fiaps at both the buccal and lingual aspects of the jaw bone. On one side of the jaw (control), the fiaps were repositioned and sutured, while on the other side (test), the defect was covered both bucally and lingually with a polytetraOuoroethylen (PTFE) membrane (Gore-Tex; W.L. Gore and Associates, Flagstaff, Ariz., USA) extending approximately 3 mm over the borders of the defect. The fiaps were repositioned on the outer surfaces of the membrane and sutured to complete coverage. Histologic analysis after healing periods of 3, 6, 9, 13 and 22 weeks demonstrated complete bone healing on the test side in all animals after 6 weeks. Little or no sign of bone healing was found on the control side even after 22 weeks (Fig. Incomplete bone healing is often observed following endodontic treatment of periapical lesions which have penetrated both the buccal and lingual/ palatal cortical bone plates (Andreasen & Rud 1972, Rud et al. 1972), the reason being the ingrowth of connective

Key words: alveolar ridge augmentation; bone regeneration; dental implants; guided tissue regeneration, osseous surgery. Accepted for publication 18 September 1990

tissue into the tunnehng defect. In an experimental study in 6 monkeys (Dahlin et al. 1990), this situation was imitated by surgically preparing transosseous defects bilaterally in the apical area of the maxillary lateral incisors including apicectomy. On the right side (test side), PTFE membranes were placed both buccally and palatally covering the entrances to the defects. The membranes were adjusted to extend about 3 mm over the margins of the bone defects. The fiaps were sutured to obtain total coverage of the wound area. The contralaterai sites served as controls as no membranes were placed. Histologic analysis after a heahng period of 3 months showed that at all test sites, the defects had healed with almost complete closure by newly formed bone, while at the control sites, none of the defects had healed with bone closure. The defects were found to be filled with a fibrous connective tissue. An intersting side observation was that, at the test sites but not at the controls, a new cementumlike tissue with inserting collagen fibers had formed, covering the cut root sur faces (Fig. 2). Insufficient bone volume is often i significant problem in conjunction wit) the placement of dental implants. In ; third study carried out in rabbits (Dahl in et al. 1989), the principle of guide* tissue regeneration was tested for it

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Fig. 1. The healing result in test and control sites. In the test sites (a, b), complete bone healing had occurred. Arrows in (b) indicate the initial borders of the bone defect. In the control sites (c, d), connective tissue from the mucosal flap has invaded the defect, thereby preventing defect closure by bone tissue.

ability to generate bone around titanium implants. The bone surface at the medial border of both tibiae in 15 New Zealand rabbits was exposed by a skin incision and subperiosteal dissection. A fixture (Nobelpharma, Gothenburg, Sweden) was inserted into both tibiae in such a way that 3 to 4 of the

coronal fixture threads were left exposed on one side of each implant. In each animal, a PTFE membrane was placed over one of the fixtures (test side) in such a way that 5 to 8 mm of the surrounding bone was covered, and that at the same time a secluded space was created between the fixture and the in-

Fig. 2. Complete bone healing of the transosseous defects in the apical area of the maxillary lateral incisors in monkeys.

ner surface of the membrane. The flap was then adapted and sutured on the outer surface of the membrane. The fixture, implanted in the contralateral tibia in the same animal, served as sham-operated control. The animals were divided into 3 groups with 5 animals in each group, allowing for healing periods of 6, 9 and 15 weeks, respectively. The results of heahng, evaluated both histologically and by photometric measurements of the amount of newly formed bone covering the titatnium implants, can be seen in Fig. 3. The amount of bone regeneration, expressed as a % of the original defect area, was much larger at the test sites (x = 99.5%; range 95,6% to 100%) compared to the controls (x = 66.4%; range 38.9% to 92.4%); (/;< 0.0001). A further application of the principle of GTR for bone regeneration may be "alveolar ridge augmentation" in situations when the ridge is too resorbed for, e.g., the placement of a dental im-

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Fig. 3. On the membrane side (a, test), all fixture threads were covered with bone, while on the control side (b, no membrane placed), only partial bone coverage had occurred.

plant or for proper function of a removable denture. The traditional treatment of such cases has been the placement of different types of grafts such as calcium

hydroxyapatite, tricalcium phosphate, etc. A study was designed to test the biological principle of GTR in reconstructing surgically-created ridge defects

Fig. 4. The concavity in the alveolar ridge preventing correct placement of a dental implant.

in beagle dogs (Seibert & Nyman 1990). The 1st, 2nd and 3rd premolars were extracted following flap elevation, and alveolar ridge defects that averaged 13 mm mesio-distally, 7 mm corono-apically and 3.5 mm bucco-lingually were produced. After a healing period of 3 months, mucoperiosteal flaps were again raised and a PTFE membrane was placed over the ridge defect overlapping the edge of the bone on the periphery of the defect but leaving an appropriate space between the defect and the membrane. The result of healing showed complete bone fill of the space provided by the membrane 90 days after the augmentation procedure, while the alveolar crest in the sham-operated controls was found to maintain the same general bone topography as at the time of "reconstructive" surgery, i.e., 3 months after defect production. The potential of the GTR method for

Fig. 5. The result of the generative treatment. A normal anatomy of the bone crest is established (a), and an implant is then placed in correct position (b).

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Bone regeneration

bone regeneration described was then tested in humans (Nyman et al. 1990), 2 examples will be presented. In 1 case, a missing mandibular 2nd premolar in a 22-year-old female should be replaced by insertion of a titanium implant. The alveolar ridge in the area was too reduced, however, in the bucco-lingual dimension for the placement of the implant (Fig. 4). A sufficient width was achieved by covering the defect with a PTFE membrane leaving an appropriate space in accordance with the principle for the animal experiments described above. This resulted in a buccolingual gain of bone and provided an adequate bone volume for the installation of a titanium implant (Fig. 5). In another case, a titanium implant (ITI Bonefit®, Strauman AG, Waldenburg, Switzerland) was inserted into an alveolus immediately after tooth extraction and secured in position by obtaining press-fit in the apical part. This re-

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is the placement of different types of bone grafts or bone substitutes into existing defects. However, harvesting of autogenous bone grafts from the patient's ihac crest, ribs or tabiae is traumatic, commercially available allografts or bone substitutes serve mainly as a scaffold for bone formation, and the incorporation of such grafts with the host bone appears unpredictable (Amler Fig. 6. The measuring 1987). gauge of a dental implant inserted into the Based on the biological principle of alveolus immediately "guided tissue regeneration" (GTR), a after tooth extraction new concept for bone regeneration has (dimensions equal been developed. This principle is based those of an implant). on the hypothesis that the different types of cells, located adjacent to a wound area, are striving to repopulate the wound during early healing. By suited in a space between the osseous means of a membrane barrier, a mechwalls of the alveolus and the implant anical hindrance to non-desirable tissue with a width of 1.5-4 mm and a depth cells can be achieved and the prohferof 5-6 mm (Fig. 6). A PTFE membrane ation of such cells into the wound space was placed over the implant and its sur- prevented, thereby giving preference to rounding osseous defect, tightly adapt- those particular cells to repopulate the ed to and extending 3-4 mm over the defect, which have the capacity to regendefect's bone borders. A re-entry oper- erate the desired type of tissue. With ation, carried out after 6 months of regard to the regeneration of bone in healing, demonstrated complete osseous osseous defects, an inert membrane barhealing of the defect with close adap- rier is placed over the defect and adapttation of the newly formed bone to the ed in close contact with the surrounding implant surfaces (Fig. 7). bone tissue. This creates a secluded space between the bone defect and the membrane into which cells exclusively Discussion originating from bone tissue can miThe result of osseous surgery, aimed at grate. Hence, osteogenesis can occur bone regeneration, is often unsatisfac- without the interference of other comtory and unpredictable. As an example, peting types of tissue cells. ingrowth of connective tissue into bony The 5 studies alluded to in the present defects jeopardizes complete bone heal- review, suggest that the principle of ing, leaving persisting bony defects. The "guided tissue regeneration" may be apmost common method hitherto advo- plied in areas of reconstructive surgery cated in order to stimulate osteogenesis exceeding the field of periodontics. One

Fig, 7. Clinical (a) and radiographical (b) demonstration of complete osseous healing of the defect with close adaptation of the newly formed bone to the implant surfaces. '

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technique. A experimental study in monkeys. Scandinavian Journal of Plastic and Reconstructive Hand Surgery 24, 13-19. Dahiin, C, Sennerby, L,, Lekholm, U., Linde, A., Nyman, S. (1989) Generation of inew bone around titanium implants using a membrane technique: an experimental study in rabbits. The International Journal of Oral and Maxiilofacial Implants 4, 19-25. Dahiin, C , Linde, A., Gottlow, J, & Nyman, S. (1988) Healing of bone defects by guided tissue regeneration. Plastic and Reconstructive Surgery 81, 672-676. Gottlow, J., Nyman, S., Lindhe, J., Karring, T. & Wennstrom, J, (1986) New attachment formation in the human periodontium by guided tissue regeneration. Case References reports. Journal of Clinical Periodontology 13, 604-616. Amler, M. H, (1987) Osteogenic potential of nonvital and synthetic implant materials. Nyman, S., Lang, N. R, Buser, D. & Bragger, Journal of Periodontology 58, 758-763, U. (1990) Bone regeneration adjacent to Andreasen, ,J, O. & Rud, J. (1972) Modes titanium dental implants using "guided of healing histologically after endodontic tissue regeneration". The International surgery in 70 cases. International Journal Journal of Oral and Maxiilofacial Implants of Oral Surgery 1, 148-160, 5, 9-14. Becker, W,, Becker, B, E,, Berg, L,, Pritchard, Nyman, S., Lindhe, J., Karring, T. & RylandJ., Caffesse, R. & Rosenberg, E, (1988) er, H. (1982) New attachment following New attachment after treatment with root surgical treatment of human periodontal isolation procedures: Report for treated disease. Journal of Clinical Periodontology class III and class II furcations and vertical 9, 290-296. osseous defects. The International Journal Nyman, S., Lindhe,J. & Karring, T, (1989) of Periodonties and Restorative Dentistry 3, Reattachment - new attachment. Textbook 2-16. of clinical periodontology, 2nd edition, ed, Dahiin, C, Gottlow, J,, Linde, A, & Nyman, Lindhe, J,, pp. 450-476. Munksgaard, S, (1990) Healing of maxillary and manCopenhagen, dibular bone defects using a membrane Pontoriero, R,, Lindhe, J., Nyman, S., Kar-

of these applications is obviously osseous surgery aimed at bone regeneration. In this respect, the principle as such may substitute for various grafting procedures hitherto advocated for bone-fiU in osseous defects and/or increase in bone dimension. It should be realized that the procedures, based on this principle, result in the regeneration of the body's own local bone. Hence, this treatment concept opens new avenues in oral and maxiilofacial surgery and probably also in several areas of general surgery.

ring, T., Rosenberg, E. & Sanavi, F. (1988) Guided tissue regeneration in degree II furcation-involved mandibular molars. A clinical study. Journal of Clinical Periodontology 15, 247-254. Pontoriero, R., Lindhe, J., Nyman, S,, Karring, T., Rosenberg, E. & Sanavi, F. (1989) Guided tissue regeneration in the treatment of furcation defects in mandibular molars. A clinical study of degree III involvements. Journal of Clinical Periodontology 16, 170-174. Rud, J., Andreasen, J, O, & Moller-Jensen, J, E. (1972) A multivariate analysis of the influence of various factors upon healing after endodontic surgery. International Journal of Oral Surgery 1, 258-271. Schallhorn, R. G, & McClain, P K. (1988) Combined osseous composite grafting, root conditioning, and guided tissue regeneration. The International Journal of Periodontics and Restorative Dentistry 4, 9-31. Seibert, J. & Nyman, S, (1990) Localized ridge augmentation in dogs: A pilot study using membranes and hydroxyapatite. Journal of Periodontology 61, 157-165, Address: iS. Nyman Department of Periodontology School of Dentistry University of Goteborg Box 33070 S-40033 Goteborg Sweden

Bone regeneration using the principle of guided tissue regeneration.

The biological principle of "guided tissue regeneration" (GTR) was developed for regenerating periodontal tissues, lost as a result of periodontal dis...
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