Restor Dent Endod.  2013 Nov;38(4):194-203.

Enamel matrix derivative for replanted teeth in animal models: a systematic review and meta-analysis

• Kim SG
• Ryu SI

Abstract

OBJECTIVES
To investigate the effect of enamel matrix derivative (EMD) on periodontal healing of replanted teeth in animal models.
MATERIALS AND METHODS
The authors searched MEDLINE, PubMed, EMBASE, Cochrane Library, Web of Knowledge and Scopus for articles published up to Oct 2012. Animal studies in which EMD was applied in transplanted or replanted teeth with adequate controls and histological data were considered. Normal periodontal healing or root resorption determined by histology after EMD was applied in replanted teeth with adequate controls was used as outcome measures. The following search strategy was used: ('Emdogain' OR 'enamel matrix proteins' OR 'enamel matrix derivative') AND ('avulsion' OR 'transplantion' OR 'autotransplantation' OR 'replantation').
RESULTS
Six animal studies were included in the final review. There was great heterogeneity in study design among included studies. Two studies with similar study designs were identified and analyzed by a meta-analysis. The pooled estimates showed a significantly higher normal healing and surface resorption and significantly less inflammatory and replacement resorption in EMD-treated groups compared with non-EMD-treated groups.
CONCLUSIONS
With the limitations of this systematic review, the use of EMD led to greater normal periodontal healing and surface root resorption and less inflammatory and replacement root resorption in the presence of periodontal ligaments. However, no definite conclusion could be drawn with regard to the effect of EMD on periodontal healing and root resorption when no periodontal ligaments exist.

Keyword

Emdogain; Enamel matrix derivative; Replantation; Root resorption

MeSH Terms

Animals*
Dental Enamel Proteins
Dental Enamel*
Models, Animal*
Outcome Assessment (Health Care)
Periodontal Ligament
Population Characteristics
Replantation
Root Resorption
Tooth*
Transplants
Dental Enamel Proteins

Figure

• 

  Figure 1 Flow chart of the selection of relevant articles.

• 

  Figure 2 Effect of EMD on normal healing in the presence of PDL. EMD, enamel matrix derivative; PDL, periodontal ligament; Std diff, standardized difference; CI, confidence interval.

• 

  Figure 3 Effect of EMD on surface resorption in the presence of PDL. EMD, enamel matrix derivative; PDL, periodontal ligament; Std diff, standardized difference; CI, confidence interval.

• 

  Figure 4 Effect of EMD on inflammatory resorption in the presence of PDL. EMD, enamel matrix derivative; PDL, periodontal ligament; Std diff, standardized difference; CI, confidence interval.

• 

  Figure 5 Effect of EMD on replacement resorption in the presence of PDL. EMD, enamel matrix derivative; PDL, periodontal ligament; Std diff, standardized difference; CI, confidence interval.

Reference

1. Andreasen JO, Andreasen FM. Avulsion. In : Andreasen JO, Andreasen FM, Andersson L, editors. Textbook and color atlas of traumatic injuries to the teeth. 4th ed. Oxford: Blackwell Munksgaard;2007. p. 444–488.

2. Marcenes W, Alessi ON, Traebert J. Causes and prevalence of traumatic injuries to the permanent incisors of school children aged 12 years in Jarague do Sul, Brazil. Int Dent J. 2000; 50:87–92. PMID: 10945187.

3. Lee JY, Divaris K. Hidden consequences of dental trauma: the social and psychological effects. Pediatr Dent. 2009; 31:96–101. PMID: 19455926.

4. Andreasen JO, Borum MK, Jacobsen HL, Andreasen FM. Replantation of 400 avulsed permanent incisors. 1. Diagnosis of healing complications. Endod Dent Traumatol. 1995; 11:51–58. PMID: 7641619.

5. Andreasen JO, Borum MK, Jacobsen HL, Andreasen FM. Replantation of 400 avulsed permanent incisors. 4. Factors related to periodontal ligament healing. Endod Dent Traumatol. 1995; 11:76–89. PMID: 7641622.

6. Malmgren B, Malmgren O. Rate of infraposition of reimplanted ankylosed incisors related to age and growth in children and adolescents. Dent Traumatol. 2002; 18:28–36. PMID: 11841463.

7. Hupp JG, Mesaros SV, Aukhil I, Trope M. Periodontal ligament vitality and histologic healing of teeth stored for extended periods before transplantation. Endod Dent Traumatol. 1998; 14:79–83. PMID: 9558520.

8. Barbakow FH, Cleaton-Jones PE, Austin JC, Vieira E. Healing of replanted teeth following typical treatment with fluoride solutions and systemic admission of thyrocalcitonin: a histometric analysis. J Endod. 1981; 7:302–308. PMID: 6942087.

9. Kum KY, Kwon OT, Spängberg LS, Kim CK, Kim J, Cho MI, Lee SJ. Effect of dexamethasone on root resorption after delayed replantation of rat tooth. J Endod. 2003; 29:810–813. PMID: 14686811.

10. Lustosa-Pereira A, Garcia RB, de Moraes IG, Bernardineli N, Bramante CM, Bortoluzzi EA. Evaluation of the topical effect of alendronate on the root surface of extracted and replanted teeth. Microscopic analysis on rats' teeth. Dent Traumatol. 2006; 22:30–35. PMID: 16422756.

11. Filippi A, Pohl Y, von Arx T. Treatment of replacement resorption by intentional replantation, resection of the ankylosed sites, and Emdogain-results of a 6-year survey. Dent Traumatol. 2006; 22:307–311. PMID: 17073922.

12. Flores MT, Andreasen JO, Bakland LK, Feiglin B, Gutmann JL, Oikarinen K, Pitt Ford TR, Sigurdsson A, Trope M, Vann WF Jr, Andreasen FM. International Association of Dental Traumatology. Guidelines for the evaluation and management of traumatic dental injuries. Dent Traumatol. 2001; 17:193–198. PMID: 11678536.

13. Heijl L, Heden G, Svärdström G, Ostgren A. Enamel matrix derivative (Emdogain) in the treatment of intrabony periodontal defects. J Clin Periodontol. 1997; 24:705–714. PMID: 9310876.

14. Hammarström L. Enamel matrix, cementum development and regeneration. J Clin Periodontol. 1997; 24:658–668. PMID: 9310870.

15. Lindskog S, Blomlöf L, Hammarström L. Repair of periodontal tissues in vivo and in vitro. J Clin Periodontol. 1983; 10:188–205. PMID: 6573345.

16. Filippi A, Pohl Y, von Arx T. Treatment of replacement resorption with Emdogain-preliminary results after 10 months. Dent Traumatol. 2001; 17:134–138. PMID: 11499763.

17. Iqbal MK, Bamaas N. Effect of enamel matrix derivative (Emdogain) upon periodontal healing after replantation of permanent incisors in beagle dogs. Dent Traumatol. 2001; 17:36–45. PMID: 11475769.

18. Ninomiya M, Kamata N, Fujimoto R, Ishimoto T, Suryono , Kido J, Nagayama M, Nagata T. Application of enamel matrix derivative in autotransplantation of an impacted maxillary premolar: a case report. J Periodontol. 2002; 73:346–351. PMID: 11922266.

19. Filippi A, Pohl Y, von Arx T. Treatment of replacement resorption with Emdogain-a prospective clinical study. Dent Traumatol. 2002; 18:138–143. PMID: 12154769.

20. Barrett EJ, Kenny DJ, Tenenbaum HC, Sigal MJ, Johnston DH. Replantation of permanent incisors in children using Emdogain. Dent Traumatol. 2005; 21:269–275. PMID: 16149922.

21. Caglar E, Tanboga I, Süsal S. Treatment of avulsed teeth with Emdogain-a case report. Dent Traumatol. 2005; 21:51–53. PMID: 15660758.

22. Chappuis V, von Arx T. Replantation of 45 avulsed permanent teeth: a 1-year follow-up study. Dent Traumatol. 2005; 21:289–296. PMID: 16149925.

23. Pohl Y, Filippi A, Kirschner H. Results after replantation of avulsed permanent teeth. II. Periodontal healing and the role of physiologic storage and antiresorptive-regenerative therapy. Dent Traumatol. 2005; 21:93–101. PMID: 15773888.

24. Araújo M, Hayacibara R, Sonohara M, Cardaropoli G, Lindhe J. Effect of enamel matrix proteins (Emdogain) on healing after re-implantation of 'periodontally compromised' roots. An experimental study in the dog. J Clin Periodontol. 2003; 30:855–861. PMID: 14710765.

25. Lam K, Sae-Lim V. The effect of Emdogain gel on periodontal healing in replanted monkeys' teeth. Oral Surg Oral Med Oral Pathol Oral Radiol Endod. 2004; 97:100–107. PMID: 14716264.

26. Molina GO, Brentegani LG. Use of enamel matrix protein derivative before dental reimplantation: a histometric analysis. Implant Dent. 2005; 14:267–273. PMID: 16160573.

27. Schjøtt M, Andreason JO. Emdogain does not prevent progressive root resorption after replantation of avulsed teeth: a clinical study. Dent Traumatol. 2005; 21:46–50. PMID: 15660757.

28. Poi WR, Carvalho RM, Panzarini SR, Sonoda CK, Manfrin TM, Rodrigues Tda S. Influence of enamel matrix derivative (Emdogain) and sodium fluoride on the healing process in delayed tooth replantation: histologic and histometric analysis in rats. Dent Traumatol. 2007; 23:35–41. PMID: 17227379.

29. Guzmán-Martínez N, Silva-Herzog FD, Méndez GV, Martín-Pérez S, Cerda-Cristerna BI, Cohenca N. The effect of Emdogain and 24% EDTA root conditioning on periodontal healing of replanted dog's teeth. Dent Traumatol. 2009; 25:43–50. PMID: 19208009.

30. Wiegand A, Attin T. Efficacy of enamel matrix derivatives (Emdogain) in treatment of replanted teeth-a systematic review based on animal studies. Dent Traumatol. 2008; 24:498–502. PMID: 18821951.

31. Higgins JPT, Altman DG. Assessing risk of bias in included studies. In : Higgins JPT, Green S, editors. Cochrane Handbook for Systematic Reviews of Interventions Version 5.1.0 The Cochrane Collaboration. 2011. updated Mar 2011. Available from: http://www.cochrane-handbook.org/.

32. Saito A, Saito E, Yoshimura Y, Takahashi D, Handa R, Honma Y, Ohata N. Attachment formation after transplantation of teeth cultured with enamel matrix derivative in dogs. J Periodontol. 2011; 82:1462–1468. PMID: 21309716.

33. Oortgiesen DA, Meijer GJ, Bronchers AL, Walboomers XF, Jansen JA. Fenestration defects in the rabbit jaw: an inadequate model for studying periodontal regeneration. Tissue Eng Part C Methods. 2010; 16:133–140. PMID: 19397470.

34. Weinberg MA, Bral M. Laboratory animal models in periodontology. J Clin Periodontol. 1999; 26:335–340. PMID: 10382571.

35. Andersson L, Andreasen JO, Day P, Heithersay G, Trope M, Diangelis AJ, Kenny DJ, Sigurdsson A, Bourguignon C, Flores MT, Hicks ML, Lenzi AR, Malmgren B, Moule AJ, Tsukiboshi M. International Association of Dental Traumatology guidelines for the management of traumatic dental injuries: 2. Avulsion of permanent teeth. Dent Traumatol. 2012; 28:88–96. PMID: 22409417.

36. Tsukiboshi M. Autotransplantation of teeth: requirements for predictable success. Dent Traumatol. 2002; 18:157–180. PMID: 12442825.

37. Söder PO, Otteskog P, Andreasen JO, Modéer T. Effect of drying on viability of periodontal membrane. Scand J Dent Res. 1977; 85:164–168. PMID: 403591.

38. Andreasen JO. Effect of extra-alveolar period and storage media upon periodontal and pulpal healing after replantation of mature permanent incisors in monkeys. Int J Oral Surg. 1981; 10:43–53. PMID: 6792094.

39. Trope M. Clinical management of the avulsed tooth: present strategies and future directions. Dent Traumatol. 2002; 18:1–11. PMID: 11841460.

40. Blomlöf J, Jansson L, Blomlöf L, Lindskog S. Root surface etching at neutral pH promotes periodontal healing. J Clin Periodontol. 1996; 23:50–55. PMID: 8636457.

41. Lyngstadaas SP, Lundberg E, Ekdahl H, Andersson C, Gestrelius S. Autocrine growth factors in human periodontal ligament cells cultured on enamel matrix derivative. J Clin Periodontol. 2001; 28:181–188. PMID: 11168744.

42. Qu Z, Laky M, Ulm C, Matejka M, Dard M, Andrukhov O, Rausch-fan X. Effect of Emdogain on proliferation and migration of different periodontal tissue-associated cells. Oral Surg Oral Med Oral Pathol Oral Radiol Endod. 2010; 109:924–931. PMID: 20399692.

43. Veis A, Tompkins K, Alvares K, Wei K, Wang L, Wang XS, Brownell AG, Jengh SM, Healy KE. Specific amelogenin gene splice products have signaling effects on cells in culture and in implants in vivo. J Biol Chem. 2000; 275:41263–41272. PMID: 10998415.

44. Kawase T, Okuda K, Momose M, Kato Y, Yoshie H, Burns DM. Enamel matrix derivative (Emdogain) rapidly stimulates phosphorylation of the MAP kinase family and nuclear accumulation of smad2 in both oral epithelial and fibroblastic human cells. J Periodontal Res. 2001; 36:367–376. PMID: 11762872.

45. Valentine JC, Pigott TD, Rothstein HR. How many studies do you need? A primer on statistical power for meta-analysis. J Educ Behav Stat. 2010; 35:215–247.