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Periodontics The biologic concept for the use of enamel matrix protein: True periodontal regeneration Hideaki Hirooka, DDS, MSc* Guided tissue regeneration procedures have been used successfiitly to reestablish periodontal attachment. However, this new attachment reportedly differs from the original attachment in strength and continuity. Enamel matrix proteins secreted by Hertwig 's epithelial sheath play an important role in cementogenesis on roots atid in the development of the periodontal attachment apparatus. Enamel matrix protein har- vested from developing porcine teeth, or enamel matrix derivative (Emdogaiii), i¡ reported to induce true periodontal regetieration (the attachment of new, aceltular cementum to the underlying dentin surface). The results of experimental and clinical trials ofEmdogain are reviewed, and the procedure for applica- tion of the material is described. (Quintessence Int 1998:29:621-630] Key words: cementogenesis, Etndogain. enamel matrix protein, periodontal disease, true periodontal regeneration Several studies have confirmed tbe efficacy of me- Clinical relevance chanical subgingival plaque control in periodontal ther- apy, irrespective of the approach used.-'-' Adequate An enamel mairix derivative has been used suc- supragingival plaque control by patients is prerequisite cessfully to reestablish the biologic processes of for the success of the periodontal treatrnent.^'' developing tooth roots and their supporting tissues. However, subgingival bacteria in deep pockets with complicated anatomy, in infrabony pockets, and in areas of furcal involvement are sometimes difficult to remove with nonsurgical therapy. In these pockets, open access eriodontal disease is an infectious disease affecting with surgical therapy may be indicated to clean the root Ptooth-supporting tissues. Clinically it results in color surfaces. chatiges of the gingiva, periodontal pocket formation, Mechanical removal of subgingival calculu.s and bleeding, clinical attachment loss, increased tooth mobil- plaque may not be enough to control subgingival infec- ity, and loss of alveolar bone on the radiographs. The ex- tion in specific cases. Thus, antibiotics are sometimes trinsic etiology of periodontal disease is bacterial plaque employed to enhance healing by suppressing specific in the periodontal pockets. bacteria that cannot be removed hy mechanical therapy The main aim of conventional periodontal therapy is alone.'' to halt and possibly reverse tbe attachment loss result- ing from the disease. To this end, initial therapy is Guided tissue regeneration or guided tissue repair? focused on removing bacterial plaque from teeth and periodontal pockets and preventing supragingival Even when inflammation has been eliminated and plaque accumulation. Subgingival plaque can be re- healthy periodontal tissue has been established after moved by nonsurgical forms of therapy, such as scaling patbogenic microorganisms are removed from peri- and root planing, or by surgical means. The efficacy of odontal pockets, the anatomy of healed defects can be a nonsurgical methods is well documented.'•- problem, particularly in areas where esthetics or mainte- nance is critical and maintenance is difficult, such as in the anterior dentition with gingival recession, infrabony •Sweden Dental Center. Tokyo, Japan. defects, and furcations. Reprint requests: Dr Hideaki Hirooka, Sweden Dental Cenler. Hibiyako- In the early 19S0s. a series of experimental studies ku.îai Building 3F, 2-2-3, Uchisaiwai-cho. Chi>oda-ku, Tokyo 100, Japan, was conducted on a procedure to regenerate the lost at- E-mail: sweden[c(?sa2..so-net.or.jp tachment apparatus, A membrane was placed under the Translated from: "The Biological Concept for the Lise of EMDOGAIN— flap to prevent epithelial downgrowth and to make a True Periodontal Regeneration", the Quintessence 1997;16(9):47-57 (in Japanese). space for periodontal re-formation." The procedure. Quintessence International 621 Hirooka termed guided tissue regeneration (GTR). was ititro- crown, the intier layer of Hertwig's epithcli^'l -heath, duced in the ciiiiical setting by Gottlow et al.^ Guided which is equivalent to inner enamel epith' ' • stimu- tisstie regeneration tlierapy has been applied to furca- lates connective tissue of mesenchymal ' '" the tion and inf'rabony sites tinder certain conditions, and its dental papilla, induces odontoblasts, an uns root efficacy has been reported,'"" dentin. Also, as in tbe crown formation, th mner layer Initially, nonresorbable membrane,s were used, and of Hertwig's epithelial sheath secretes protein on the these had to be removed dttring a second suigery. Tbis newly formed root dentin surface. Thi.'. protein is second surgery is tiot only a burden for patients but also thought be the same as the above-mentioned enamei a potential trauma to iratnature periodontal tisstte Ltnder- matrix proteins that induce ameloblasts," going regeneration. Adverse reactions, ¡ncluding pocket Simultaneously, Hertwig's epithelial root sheath breaks formation and gingival recession, have been reported.'- up and becomes the epithelial rests of Malassez. As the In tbe 1990s, one-step procedures utilizing resorbable two epithelium layers of ectodermal origin are divided, membranes were developed, and these have been re- the enamel matrix proteins on the dentin surface stimulate ported to have favorable results," mesenchymal cells around the dental follicle, and cemen- However, histologie specimens from some sites re- toblasts are indticed on the root dentin surface, resulting generated with the GTR technique revealed that there is in the formation of root cementum.'''This root cementum, often an artifactual defect between regenerated cemen- which is produced in the initial stage, cotitains no cells tum and root dentin,'•' It has been claimed that the new and is called acelhdar cementum. Principal fibers are em- attachment between regenerated cementum obtained bedded in this acellular cementum, and tbe cementum from GTR procedures and root dentin may not be as functions to maintain attachment to the tooth ¡Fig 1). strong as tbe attachment between original cementum On the other hand, if Hertwig's epithehal sheath is and root dentin." not divided and the enamel proteins are not exposed to Because cementum resulting from GTR therapy ap- mesenchymal cells, an enamel pearl may be produced parently is different from cementum formed during on the root dentin surface. tootb development (acellular cementum). the appropri- Following the production of root cementum, a series ateness of the term regeneration in the context of GTR of cell inductions occur in the intrinsic dental follicle, therapy has been questioned.'^ Recently, some authors and the periodontal ligament and alveolar bone proper have started using the term ti-ue periodontal regenera- arc formed. tion, which has been defined as "healing after periodon- tal treatment that results in the regain of lost supporting Development of enamel matrix derivative tissues including new acellular cementum attached to the underlying dentin surface, a new periodontal liga- Thus, enamel matrix proteins secreted by Hertwig's ment with functionally oriented collagen fibers inserting epithelial sheath play an important role not only in into the new cementum and new alveolar bone attached cementogenesis on roots but also in the development of to the periodontal ligament.'"'^ the periodontal attachment apparatus. Research was focused on enamel matrix proteins in a series of The role of enamel matrix protein in cementogenesis studies.-"--- These proteins were applied for the regener- ation of tooth-supporting tissues that were lost to peri- In the embryonic stage, ectodermal epithelium becomes odontal disease. invaginated and changes into inner and outer enamel The enamel matrix protein harvested from developing epithelium, forming the enamel organ. Inner enamel porcine teeth is called enamel matrix derivative (EMD), epithelium stimulates connective tissue of mesenchymal Stable, freeze-dried EMD was purified {Emdogain, origin in the dental papilla, induces odontoblasts, and Biora) for use in periodontal tissue regeneration (Fig 2). creates coronal dentin. Simultaneously, on the newly formed dentin surface, inner enamel epithelium secretes Experimental study of enamel matrix derivative enamel matrix protein (primarily composed of amelo- genin), which induces ameloblasts on the dentinal sur- Hammarstrom et al-' used Emdogain to attempt face in the enamei organ and fotms enamel. periodontal tissue regeneration in monkeys. After a After Ihe coronal portion of the tooth (crown) is mucoperiosteal flap extending from tbe maxillaty ca- formed, hoth inner and outer enamel epithelium con- nine to the maxillary first molar was elevated bilater- tinue to proliferate apically in the dental follicle. These ally, the buccal alveolar botie, periodontal ligairnrnt, and two cell layers of ectodermal origin are called Hertwig 's cementutn were removed with a dental bur, cre.i mg an epithelial root sheath. Just as in dentinogenesis in the artificial dehiscence defect (Fig 3). On the test site. ..ifter 622 Volume 29, Number lo. 199g H i rook a Fig 1 i-iertwigs epitheiiai root sheath (blue bundles) Fig Z Emdogain is packed under strict steriiization secretes enamel protein (green line; arrows) on the conditions. newiy formed root dentin surface. Cementobiasts (red) are induced and aceiiular extrinsic fiber cementum (blue) is formed. Fig 3 Artificiai dehiscence defects Fig 4 Atte/ EMD (green)

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