bs_bs_banner

Aust Endod J 2013; 39: 171–175

L I T E R AT U R E R E V I E W

Efficacy of the enamel matrix derivative in direct pulp capping procedures: A systematic review aej_357

171..175

Khalid Al-Hezaimi, MSc1; Fawad Javed, PhD1; Khalid Al-Fouzan, MSc1,2; and Franklin Tay, PhD3 1 Engineer Abdullah Bugshan Research Chair for Growth Factors and Bone Regeneration, 3D Imaging and Biomechanical Lab, College of Applied Medical Sciences, King Saud University, Riyadh, Saudi Arabia 2 Division of Endodontics, King Abdulaziz Medical City, National Guard Hospital, Riyadh, Saudi Arabia 3 Department of Endodontics, School of Dentistry, Medical College of Georgia, Augusta, Georgia, USA

Keywords dental, dentine, direct pulp capping, enamel matrix derivative, treatment. Correspondence Dr Khalid Al-Hezaimi, Growth Factors and Bone Regeneration, 3D Imaging and Biomechanical Lab, College of Applied Medical Sciences, King Saud University, Riyadh 60169, Saudi Arabia. Email: [email protected] doi:10.1111/j.1747-4477.2012.00357.x

Abstract The aim was to review the efficacy of the enamel matrix derivative (EMD) in direct pulp capping (DPC) procedures. Databases were explored using the following keywords: ‘dental’, ‘dentine’, ‘enamel matrix derivative’, ‘pulp capping’ and ‘treatment’. The inclusion criteria were: (i) original studies; (ii) human and animal studies; (iii) reference list of potentially relevant original and review articles; (iv) intervention: effect of EMD on pulp-capping procedures; and (v) articles published only in English. Eight studies (four human and four animal) were included. Among the human studies, two studies reported that EMD is a more efficient DPC procedure compared with calcium hydroxide (Ca(OH)2). One study reported Ca(OH)2 to be more efficient for DPC than EMD. One study reported no difference in the efficacies between EMD and Ca(OH)2 for DPC. All animal studies reported EMD to be more effective in reparative dentine formation in comparison with Ca(OH)2. EMD can provide favourable results in DPC procedures.

Introduction Direct pulp capping (DPC) is a commonly used procedure for the treatment of small accidental pulp exposures in the newly erupted permanent dentition (1–5). Although calcium hydroxide (Ca(OH)2) has been traditionally used for DPC (6,7), other studies reported that the strong alkaline nature of the material may induce necrosis of the pulp (8,9). The efficacy of Ca(OH)2 in DPC has also been challenged due to its poor sealing quality, degradation over time and the presence of tunnel defects in dentine bridges (10). Such disadvantages of Ca(OH)2 led to the development of new pulp-capping materials, including bioactive molecules and enamel matrix protein (6,10–16). It is known that the enamel matrix proteins play biological roles in the formation of dentine, acellular cementum and alveolar bone during tooth development (17). Bone sialoprotein and osteopontin are major noncollagenous protein expressed in bone and dentine (18,19). Enamel matrix proteins have been reported to increase the levels of mineralization markers (including

© 2012 The Authors Australian Endodontic Journal © 2012 Australian Society of Endodontology

bone sialoprotein and osteopontin) in odontoblasts (20). Based on this concept, the enamel matrix derivative (EMD) was formulated. The regenerative process of EMD consists of differentiation of odontoblasts with consequent dentine formation and pulpal wound healing without affecting the vitality of the remaining pulp in a manner similar to normal dentinogenesis (13–21). Amelogenin is the principal component of EMD that has an important role in dentine formation during dentinogenesis (17,22–24). When a pulp wound is exposed to EMD, a significant amount of reparative dentine-like tissue is formed with successive neogenesis of normal pulp tissues, in a manner similar to the classical woundhealing process. This process appears to imitate normal dentinogenesis due to the high fractions of amelogenin and amelin found in EMD (17,22–24). EMD has also been reported to contain growth factors such as transforming growth factor-beta 1 and small amelogenin peptides that are actively involved in cell signalling to stimulate matrix formation and mineralization (11,22,25,26). These growth factors are recognized as mediators in 171

Enamel Matrix Derivative and Pulp Capping

K. Al-Hezaimi et al.

Table 1 List of excluded studies and main reasons for exclusion Paper

Reason for exclusion

Min KS, Yang SH, Kim EC. The combined effect of mineral trioxide aggregate and enamel matrix derivative on odontoblastic differentiation in human dental pulp cells. J Endod 2006; 35: 847–51 Jiang J, Goodarzi G, He J et al. Emdogain-gel stimulates proliferation of odontoblasts and osteoblasts. Oral Surg Oral Med Oral Pathol Oral Radiol Endod 2006; 102: 698–702. Innes N. Enamel matrix derivative for direct pulp capping. Evid Based Dent 2010; 11: 45–6.

Cell culture study

processes such as tissue homeostasis, inflammation, healing and neogenesis. EMD has been tested as a pulp-capping material in human (5) as well as animal studies (12,14,15). The results showed EMD to be in close proximity to the newly formed hard tissue, thereby supporting the hypothesis that EMD is a more effective DPC agent that promotes hard tissue formation in exposed human pulps compared with Ca(OH)2 (5,12,14,15). Nevertheless, Garrocho-Rangel et al. (2) reported no significant differences in the efficacies of EMD and Ca(OH)2 as DPC materials. Although clinical and experimental studies on DPC with EMD have demonstrated promising results, the results remain debatable. Thus, the aim of the present systematic review was to examine the efficacy of the EMD in pulp-capping procedures. The focused question to be answered (a problem, intervention, comparison and outcome (PICO) question) may be framed as follows: ‘In vital teeth with pulpal exposures, does DPC with calcium hydroxide, compared with enamel matrix derivative, result in a worse clinical or histologic outcome?’

Cell culture study Commentary

The second step was to hand search the bibliography of the original and review articles that were obtained from the computer search. Titles and abstracts of the retrieved articles were screened by the authors and checked for agreement. After final selection of the papers, full texts of the studies that fulfilled the selection criteria were retrieved and processed for data extraction. The following data were extracted from all the selected studies: investigators and year of publication of the study, aim, study design, study participants or animal models (in human and animal studies, respectively), numbers of teeth included, follow-up duration, and conclusion. The initial search yielded 12 studies. Four studies that did not fulfil the eligibility criteria were excluded (Table 1). Eight studies (four human (2–5) and four animal (13–16) that fulfilled the inclusion criteria were included (Tables 2,3). Because only a limited number of studies fulfilled our inclusion criteria, a qualitative review was performed to primarily summarise the pertinent data. No metaanalyses were performed to analyse the data.

Results Materials and methods Inclusion and exclusion criteria The inclusion criteria were: (i) original studies; (ii) human and animal studies; (iii) reference list of potentially relevant original and review articles; (iv) intervention: effect of EMD on pulp-capping procedures; and (v) articles published only in English. The exclusion criteria were historic reviews, cell culture studies, commentaries, letters to the editor and unpublished articles.

Search strategy The MEDLINE/PubMed (National Library of Medicine, Bethesda, MD, USA) and Google scholar databases were first searched for appropriate articles addressing the focused question. Databases were explored from 1949 to 2010 (last accessed 2 November 2010) using the following keywords in various combinations: ‘dental’, ‘dentine’, ‘enamel matrix derivative’, ‘pulp capping’ and ‘treatment’. A similar search was also conducted using EMBASE and Wiley Online Database. 172

Of the eight included studies, six studies reported that DPC with EMD yields favourable outcomes (3,5,13–16).

Human studies The numbers of participants ranged from 1 female subject to 45 individuals (2–5). The numbers of teeth investigated ranged from 1 tooth to 30 teeth. The size of the exposure defects ranged between 1 and 2 mm. The duration of follow-up after EMD treatment ranged from approximately 3 months up to 1 year. The teeth included in the ‘test-group’ received EMD dressings for DPC, whereas teeth in the ‘control-group’ received Ca(OH)2 dressings. In two (2,3) out of the four studies, the efficacy of EMD for DPC was tested in primary molars; in the remaining studies (4,5), the effectiveness of the material was tested in the permanent dentition. One study (2) reported no significant difference between the efficacies of EMD and Ca(OH)2 as DPC materials. Two studies (3,5) reported that EMD enhanced the formation of reparative dentine when compared with Ca(OH)2. Results from Kiatwateeratana et al. (4) indicated that DPC with Ca(OH)2 has more

© 2012 The Authors Australian Endodontic Journal © 2012 Australian Society of Endodontology

To compare the clinical and radiographic efficacy of EMD and Ca(OH)2 as DPC materials for primary molars To assess the efficacy of EMD as a DPC material in primary first molars To compare the effect of EMD and Ca(OH)2 on exposed human pulp tissues To compare the effects of EMD and Ca(OH)2 on experimentally exposed human pulps and to register post-operative symptoms

Garrocho-Rangel et al. (2)

18

8 subjects

© 2012 The Authors

Australian Endodontic Journal © 2012 Australian Society of Endodontology

To investigate the efficacy of EMD as a DPC material after pulp amputations of upper first molars To assess the efficacy of EMD in DPC procedures in dogs To assess the efficacy of EMD to induce reparative dentine formation in pulpotomized teeth To assess the effects of EMD on exposed pulp tissue of premolars of adult miniature swines

Igarashi et al. (12) Ishizaki et al. (13) Nakamura et al. (14) Nakamura et al. (15)

1–2 2 2

32 36 22

2 adult mongrel dogs 11 adult miniature swine 4 adult miniature swine

0.8

47

Diameter of exposure defect (mm)

2

2

1

1

~3

6

12

12

~2

~2

~2

~1

DPC of a primary molar with EMD may represent a promising treatment in small pulp exposures DPC with Ca(OH)2 had more favourable reparative effects compared with those capped with EMD. DPC with EMD enhances formation of reparative dentine with post-operative symptoms being less frequent in comparison with Ca(OH)2.

No significant difference in the efficacies of EMD and Ca(OH)2 as DPC materials for primary molars

Conclusion

EMD is a biologically active DPC agent that induces pulp wound healing and dentine formation. DPC with EMD has more favourable reparative effects compared with those capped with Ca(OH)2.

EMD enhances formation of reparative dentine and dentine bridges during wound healing of amputated rat molar pulp. EMD may play a positive role in DPC procedures.

Conclusion

Follow-up (months)

Follow-up (months)

Diameter of exposure defect (mm)

Wistar rats

Animal model

Ca(OH)2, calcium hydroxide; DPC, direct pulp-capping; EMD, enamel matrix derivative.

Aim

Publication

Table 3 Characteristics of the four animal studies selected for review in the present study

Number of teeth

30

15 subjects

1

45 subjects

6.7-year-old female



Study subjects

Ca(OH)2, calcium hydroxide; DPC, direct pulp capping; EMD, enamel matrix derivative.

Garrocho-Rangel et al. (3) Kiatwateeratana et al. (4) Olsson et al. (5)

Aim

Publication

Number of teeth

Table 2 Characteristics of the four human studies selected for review in the present study

K. Al-Hezaimi et al. Enamel Matrix Derivative and Pulp Capping

173

Enamel Matrix Derivative and Pulp Capping

favourable outcomes compared with EMD in terms of reparative dentine formation.

Animal studies Of the four studies included in the present review, the numbers of teeth ranged from 22 to 47 teeth and the size of the exposure defects ranged between 0.8 and 2 mm. In one study performed using Wistar rats as the animal model (13), the pulp status was assessed 1 month after DPC. With the remaining studies using mongrel dogs (13) or miniature swines (14,15) as the animal model, post-operative evaluation was performed approximately 2 months following DPC. Results from all animal studies reported EMD to be more effective in forming reparative dentine over exposed pulp tissues when compared with Ca(OH)2.

Discussion The comprehensive search in the present study indicated that only a limited number of studies had performed on the efficacy of EMD in pulp-capping procedures. According to Murray et al. (27), microleakage from the margins of the capping material into the pulp chamber may lead to bacterial contamination, thereby inducing post-operative complications. Olsson et al. (5) employed glass-ionomer and zinc-oxide eugenol cements as sealing materials to prevent bacterial microleakage into the pulp. According to the results from that study, EMD appeared to be a favourable DPC material when compared with Ca(OH)2. However, whether this favourable outcome should be credited entirely to EMD treatment is debatable. Garrocho-Rangel et al. (2) compared the clinical and radiographic efficacy of EMD and Ca(OH)2 as DPC materials. The authors used a dentine adhesive and glass ionomer coats in order to prevent microleakage. The results showed no significant differences between the clinical and radiographic efficacy of EMD and Ca(OH)2 during DPC of exposed pulp tissues. It may therefore be hypothesised that adequate sealing of the exposed pulp should be the primary objective in DPC protocols and the role of the capping material (either EMD or Ca(OH)2) is only secondary in nature. This hypothesis may also explain the results reported by Kiatwateeratana et al. (4) that reported that Ca(OH)2 was a more effective pulpcapping agent when compared with EMD. In that study, the cavity was also covered in layers with intermediate restorative material (Dentsply-Caulk, Milford, DE, USA) and a resin-bonded glass ionomer cement. Calcium hydroxide is a strong alkali that may contribute to reducing bacterial contamination of the pulp tissues. Thus, microbial invasion may affect the EMD-treated pulps more often than those capped with Ca(OH)2. In 174

K. Al-Hezaimi et al.

the study by Olsson et al. (5), the pulpal inflammatory response was found to be more pronounced in teeth treated with EMD than those capped with Ca(OH)2. This highlights that small, accidentally exposed pulp exposures should be sealed as soon as possible in order to avoid microbial contamination. Although operative debris such as dentine chips may be considered to be advantageous because they stimulate dentine bridge formation, they may also act as opportunistic contaminants (28,29). Such debris may often be contaminated with bacteria, which can infiltrate the pulp tissue to stimulate immune reactions. In severe cases, pulp necrosis may occur, thereby preventing the formation of dentine bridges (30). From the literature reviewed, accidental pulpal exposures up to 2 mm in diameter responded positively to DPC regardless of the capping material. An example is the study by Garrocho-Rangel et al. (2) wherein pulpal exposures of 1 mm diameter were sealed with either EMD or Ca(OH)2. The result of that study indicated that there was no significant difference between the efficacy of EMD and Ca(OH)2 in DPC protocols. It may therefore be hypothesised that small pulpal exposures may prevent the dentine chips to contaminate the underlying pulp tissues, thereby contributing to the overall success of the DPC procedure. Assessment of DPC in larger pulpal exposures (greater than 2 mm in diameter) requires further clinical investigations. Long-term follow-up results may assist in evaluating the overall success or failure of any restorative procedure. According to Barthel et al. (30), the success of the DCP of teeth is 37% after 5 years and 13% after 10 years. From the literature reviewed, we found it difficult to predict the long-term success rate of DPC with EMD. This is because there were only two clinical studies that performed follow-up after 12 months of pulp capping, with opposing conclusions. One of those studies reported that EMD produced promising results in DPC protocols (3), whereas no significant difference between the efficacies of EMD and Ca(OH)2 was observed in the other study (2). Further clinical studies with long-term follow-up durations should be performed to achieve a better understanding of the efficacy of EMD in DPC procedures. In conclusion, EMD appears to produce favourable results when used in DPC procedures. However, in order to categorise EMD as the ‘material of choice’ for DPC, further clinical trials with long-term follow-up durations are needed.

References 1. Yamamura T. Differentiation of pulpal cells and inductive influences of various matrices with reference to pulpal wound healing. J Dent Res 1985; 64: 530–40.

© 2012 The Authors Australian Endodontic Journal © 2012 Australian Society of Endodontology

Enamel Matrix Derivative and Pulp Capping

K. Al-Hezaimi et al.

2. Garrocho-Rangel A, Flores H, Silva-Herzog D, Hernandez-Sierra F, Mandeville P, Pozos-Guillen AJ. Efficacy of EMD versus calcium hydroxide in direct pulp capping of primary molars: a randomized controlled clinical trial. Oral Surg Oral Med Oral Pathol Oral Radiol Endod 2009; 107: 733–8. 3. Garrocho-Rangel A, Flores H, Silva-Herzog D, RosalesIbañez R, Pozos-Guillen AJ. Direct pulp capping in primary molars with enamel matrix derivative: report of a case. J Clin Pediatr Dent 2009; 34: 9–12. 4. Kiatwateeratana T, Kintarak S, Piwat S, Chankanka O, Kamaolmatyakul S, Thearmontree A. Partial pulpotomy on caries-free teeth using enamel matrix derivative or calcium hydroxide: a randomized controlled trial. Int Endod J 2009; 42: 584–92. 5. Olsson H, Davies JR, Holst KE, Schröder U, Petersson K. Dental pulp capping: effect of Emdogain Gel on experimentally exposed human pulps. Int Endod J 2005; 38: 186–94. 6. Glass RL, Zander HA. Pulp healing. J Dent Res 1949; 28: 97–107. 7. Zander HA, Glass RL. The healing of phenolized pulp exposures. 1949. Oral Surg Oral Med Oral Pathol Oral Radiol Endod 2005; 100 (Suppl 2): S97–101. 8. Seltzer S, Bender IB. Some influences affecting repair of the exposed pulps of dogs’ teeth. J Dent Res 1958; 37: 678–87. 9. Furey A, Hjelmhaug J, Lobner D. Toxicity of Flow Line, Durafill VS, and Dycal to dental pulp cells: effects of growth factors. J Endod 2010; 36: 1149–53. 10. Schuurs AH, Gruythuysen RJ, Wesselink PR. Pulp capping with adhesive resin-based composite vs. calcium hydroxide: a review. Endod Dent Traumatol 2000; 16: 240–50. 11. Jiang J, Goodarzi G, He J et al. Emdogain-gel stimulates proliferation of odontoblasts and osteoblasts. Oral Surg Oral Med Oral Pathol Oral Radiol Endod 2006; 102: 698–702. 12. Igarashi R, Sahara T, Shimizu-Ishiura M, Sasaki T. Porcine enamel matrix derivative enhances the formation of reparative dentine and dentine bridges during wound healing of amputated rat molars. J Electron Microsc (Tokyo) 2003; 52: 227–36. 13. Ishizaki NT, Matsumoto K, Kimura Y, Wang X, Yamashita A. Histopathological study of dental pulp tissue capped with enamel matrix derivative. J Endod 2003; 29: 176–9. 14. Nakamura Y, Hammarström L, Matsumoto K, Lyngstadaas SP. The induction of reparative dentine by enamel proteins. Int Endod J 2002; 35: 407–17. 15. Nakamura Y, Hammarström L, Lundberg E et al. Enamel matrix derivative promotes reparative processes in the dental pulp. Adv Dent Res 2001; 15: 105–7. 16. Accorinte ML, Loguercio AD, Reis A et al. Response of human dental pulp capped with MTA

© 2012 The Authors Australian Endodontic Journal © 2012 Australian Society of Endodontology

17.

18.

19.

20.

21.

22.

23.

24.

25.

26.

27.

28.

29.

30.

and calcium hydroxide powder. Oper Dent 2008; 33: 488–95. Hammarström L. Enamel matrix, cementum development and regeneration. J Clin Periodontol 1997; 24: 658–68. Mizuno M, Imai T, Fujisawa R, Tani H, Kuboki Y. Bone sialoprotein (BSP) is a crucial factor for the expression of osteoblastic phenotypes of bone marrow cells cultured on type I collagen matrix. Calcif Tissue Int 2000; 66: 388–96. Fujisawa R, Kuboki Y. Changes in levels of osteonectin in bovine dentin during tooth development. Arch Oral Biol 1989; 34: 89–92. Weishaupt P, Bernimoulin JP, Trackman P, Hägewald S. Stimulation of osteoblasts with Emdogain increases the expression of specific mineralization markers. Oral Surg Oral Med Oral Pathol Oral Radiol Endod 2008; 106: 304–8. Papagerakis P, MacDougall M, Hotton D, BailleulForestier I, Oboeuf M, Berdal A. Expression of amelogenin in odontoblasts. Bone 2003; 32: 228–40. Veis A, Tompkins K, Alvares K et al. Specific amelogenin gene splice products have signaling effects on cells in culture and in implants in vivo. J Biol Chem 2000; 275: 41263–72. Viswanathan HL, Berry JE, Foster BL et al. Amelogenin: a potential regulator of cementum-associated genes. J Periodontol 2003; 74: 1423–31. Zhang W, Ahluwalia IP, Yelick PC. Three dimensional dental epithelial-mesenchymal constructs of predetermined size and shape for tooth regeneration. Biomaterials 2010; 31: 7995–8003. Kawase T, Okuda K, Yoshie H, Burns DM. Anti-TGF-b antibody blocks enamel matrix derivative-induced upregulation of P21WAF1/cip1 and prevents its inhibition of human oral epithelial cell proliferation. J Periodontal Res 2002; 37: 255–62. Nebgen DR, Inoue H, Sabsay B, Wei K, Ho CS, Veis A. Identification of the chondrogenic inducing activity from bovine dentin (bCIA) as a low molecular mass amelogenin poplypeptide. J Dent Res 1999; 78: 1484–94. Murray PE, Hafez AA, Smith AJ, Windsor LJ, Cox CF. Histomorphometric analysis of odontoblast-like cell numbers and dentine bridge secretory activity following pulp exposure. Int Endod J 2003; 36: 106–16. Gwinnett AJ, Tay F. Early and intermediate time response of the dental pulp to an acid etch technique in vivo. Am J Dent 1998; 11: S35–S44. Fitzgerald M, Chiego DJ Jr, Heys DR. Autoradiographic analysis of odontoblast replacement following pulp exposure in primate teeth. Arch Oral Biol 1990; 35: 707–15. Barthel CR, Rosenkranz B, Leuenberg A, Roulet JF. Pulp capping of carious exposures: treatment outcome after 5 and 10 years: a retrospective study. J Endod 2000; 26: 525–8.

175

Efficacy of the enamel matrix derivative in direct pulp capping procedures: a systematic review.

The aim was to review the efficacy of the enamel matrix derivative (EMD) in direct pulp capping (DPC) procedures. Databases were explored using the fo...
124KB Sizes 0 Downloads 0 Views