References

Melcher AH. Cells of periodontium: their role in the healing of wounds. Ann R Coll Surg Engl. 1985; 67:130-131
Melcher AH. On the repair potential of periodontal tissues. J Periodontol. 1976; 47:256-260 https://doi.org/10.1902/jop.1976.47.5.256Saline/ultrasonicwaterjet
Karring T, Nyman S, Lindhe J. Healing following implantation of periodontitis affected roots into bone tissue. J Clin Periodontol. 1980; 7:96-105 https://doi.org/10.1111/j.1600-051x.1980.tb01952.x
Nyman S, Lindhe J, Karring T, Rylander H. New attachment following surgical treatment of human periodontal disease. J Clin Periodontol. 1982; 9:290-296 https://doi.org/10.1111/j.1600-051x.1982.tb02095.x
Chung YM, Lee JY, Jeong SN. Comparative study of two collagen membranes for guided tissue regeneration therapy in periodontal intrabony defects: a randomized clinical trial. J Periodontal Implant Sci. 2014; 44:194-200 https://doi.org/10.5051/jpis.2014.44.4.194
Sanz M, Tonetti MS, Zabalegui I Treatment of intrabony defects with enamel matrix proteins or barrier membranes: results from a multicenter practice-based clinical trial. J Periodontol. 2004; 75:726-733 https://doi.org/10.1902/jop.2004.75.5.726
Cortellini P, Tonetti MS. Focus on intrabony defects: guided tissue regeneration. Periodontol 2000. 2000; 22:104-132 https://doi.org/10.1034/j.1600-0757.2000.2220108.x
Hammarström L, Heijl L, Gestrelius S. Periodontal regeneration in a buccal dehiscence model in monkeys after application of enamel matrix proteins. J Clin Periodontol. 1997; 24:669-677 https://doi.org/10.1111/j.1600-051x.1997.tb00248.x
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 https://doi.org/10.1111/j.1600-051x.1997.tb00253.x
Sculean A, Kiss A, Miliauskaite A Ten-year results following treatment of intra-bony defects with enamel matrix proteins and guided tissue regeneration. J Clin Periodontol. 2008; 35:817-824 https://doi.org/10.1111/j.1600-051X.2008.01295.x
Takei HH, Han TJ, Carranza FA Flap technique for periodontal bone implants. Papilla preservation technique. J Periodontol. 1985; 56:204-210 https://doi.org/10.1902/jop.1985.56.4.204
Trombelli L, Farina R, Franceschetti G, Calura G. Single-flap approach with buccal access in periodontal reconstructive procedures. J Periodontol. 2009; 80:353-263
Cortellini P, Tonetti MS. Improved wound stability with a modified minimally invasive surgical technique in the regenerative treatment of isolated interdental intrabony defects. J Clin Periodontol. 2009; 36:157-163 https://doi.org/10.1111/j.1600-051X.2008.01352.x
Esposito M, Coulthard P, Thomsen P, Worthington HV. Enamel matrix derivative for periodontal tissue regeneration in treatment of intrabony defects: a Cochrane systematic review. J Dent Educ. 2004; 68:834-844
Graziani F, Gennai S, Petrini M Enamel matrix derivative stabilizes blood clot and improves clinical healing in deep pockets after flapless periodontal therapy: a randomized clinical trial. J Clin Periodontol. 2019; 46:231-240 https://doi.org/10.1111/jcpe.13074
Aimetti M, Ferrarotti F, Mariani GM, Romano F. A novel flapless approach versus minimally invasive surgery in periodontal regeneration with enamel matrix derivative proteins: a 24-month randomized controlled clinical trial. Clin Oral Investig. 2017; 21:327-337 https://doi.org/10.1007/s00784-016-1795-2
Wennström JL, Lindhe J. Some effects of enamel matrix proteins on wound healing in the dento-gingival region. J Clin Periodontol. 2002; 29:9-14 https://doi.org/10.1034/j.1600-051x.2002.290102.x
Sato S, Kitagawa M, Sakamoto K Enamel matrix derivative exhibits anti-inflammatory properties in monocytes. J Periodontol. 2008; 79:535-540 https://doi.org/10.1902/jop.2008.070311

Enamel Matrix Derivative Use in Dentistry: An Update

From Volume 49, Issue 4, April 2022 | Pages 301-306

Authors

Michael Daldry

Foundation Dentist, Dental Centre, Bournemouth

Articles by Michael Daldry

Email Michael Daldry

Jaini Shah

Foundation Dentist, Poynters Road Dental Practice, Dunstable

Articles by Jaini Shah

Ewen McColl

BSc(Hons), BDS, MFDS, FDS RCPS, MCGDent, MRD RCS Ed, MClinDent, FDS RCS(Rest Dent), FHEA, FDTF(Ed), , BSc (Hons), FCGDent, FDTFEd, FFD RCSI

Director of Clinical Dentistry; Peninsula Dental School, University of Plymouth

Articles by Ewen McColl

Email Ewen McColl

Rob Witton

Director of Community-based Dentistry, Peninsula Dental School, University of Plymouth

Articles by Rob Witton

Abstract

Following a review of periodontal wound healing, this article discusses techniques designed to optimise periodontal wound healing, including guided-tissue regeneration and periodontal regeneration using enamel matrix derivatives. Enamel matrix derivatives are porcine derived, and are thought to stimulate differentiation, proliferation, migration and mineralization in cells found in periodontal tissues. This article charts the development in surgical techniques to optimise outcomes from regenerative techniques, in addition to explaining complications and how they can be avoided. Recent research relating to use of enamel matrix derivatives as an adjunct to non-surgical periodontal therapy is described, and while the evidence is limited to a single research study, the present article discusses the potential use of this technique in practice, accepting that a cost–benefit analysis would be required for individual patients.

CPD/Clinical Relevance: An update for practitioners on developments in use of enamel matrix derivatives in dentistry to allow informed decision-making on the utility and value of using flapless techniques.

Article

After most cases of non-surgical or surgical periodontal therapy, reparative wound healing occurs with the formation of a long junctional epithelium, reduction in inflammation, and maturation of the collagen in the periodontal connective tissue. However, this fails to replicate the previous healthy periodontal architecture and function. Regenerative periodontal techniques aim to replicate the original form and function of the periodontium, by allowing key elements, such as cementum, the periodontal ligament and bony architecture, to reform.1

Background

It is now well understood that periodontal health is a balance between the microbial biofilm (Figure 1) and the host response, and bacterial dysbiosis, or a change in this balance, may lead to both hard and soft tissue destruction.

Figure 1. Diagram illustrating: (a) healthy gingival attachment; (b) periodontal breakdown mechanisms; and (c) reparative healing, resulting in long junctional epithelium and clinical attachment loss.

In 1976, Melcher suggested that wound healing following periodontal treatment was determined by the first type of cell to repopulate the root surface. This cell type would then determine the nature of the clinical attachment that forms.2 In a series of studies carried out by Lindhe and Karring on periodontally compromised teeth, it was shown that, if the first cell to populate the root surface was epithelium, reparative healing occurred and a new attachment was formed, creating a long junctional epithelium (Figure 1).3 Nyman expanded on these findings and established that cells from the periodontal ligament held the key to regeneration of the periodontium.4 This understanding of periodontal healing methods led to the development of surgical periodontal regeneration therapy, where practitioners have explored the use of graft types and inhibition methods, such as guided tissue regeneration (GTR), and the introduction of enamel matrix proteins (Emdogain, Straumann, Basel, Switzerland), to optimize periodontal healing (Figure 2).

Figure 2. Timeline showing the history of key periodontology discoveries.

Guided tissue regeneration

The concept of GTR is based around the idea of limiting the access of epithelial cells to the root surface.5 This is achieved by placing a physical barrier to ensure cells from the periodontal ligament contact the root surface first, preventing long junctional epithelial formation.5 The technique involves using a range of barrier membranes, but largely relies on raising extensive surgical flaps to allow membrane placement, often leading to complications.6 GTR is shown to have the greatest impact when used in narrow, deep, three-walled defects (Figure 3); 7 however, case selection is of paramount importance, and exposure of membranes, alongside other post-operative healing complications are not uncommon.

Figure 3. Diagram schematic to illustrate bony defect classifications: (a) one-walled defect; (b) two-walled defect; and (c) three-walled defect.

Enamel matrix proteins

The biological concept of using enamel matrix proteins (EMPs: Emdogain) is the hope that they mimic the cells from Hertwig's epithelial root sheath in the formation of the periodontium8. EMPs are thought to be deposited onto the root surface and are the prerequisite needed to generate cementum. As cementum production occurs, stimulation of the periodontal ligament follows.9 The use of Emdogain has been shown to accelerate wound closure, reduce inflammation and increase predictability of healing outcomes.10

Using EMPs clinically is less technique sensitive, but still relies on the need for good primary closure; leading to a range of surgical flap designs to optimise apposition.11,12,13. Figure 4 shows a pre-surgical radiograph prior to Emdogain surgery (Figure 5) distal to the LR6 where a modified papilla preservation flap has been used to ensure good primary closure following application of Emdogain. Figure 6 shows the radiographic outcome of the surgery, with good bony infill of the two-walled vertical bone defect.

Figure 4. Pre-operative radiograph of Emdogain surgery distal to LR6.
Figure 5. Intra-surgical view of a modified papilla preservation flap exposing a bony defect, before being treated with Emdogain.
Figure 6. Radiographic evidence of bony infill and improved healing using Emdogain surgically on LR6.

Surgical flap designs

Improving surgical flap designs helps to produce predictable results, assisting healing, improved patient comfort and decreased complications. It should be noted, however, that when carrying out any surgical technique, access and vision should be optimal, and an awareness of vital structures is important to limit adverse complications. Takei's papilla preservation technique (Figure 7) allows support for clot stabilization and close apposition of the surgical site,11 all contributing to primary wound healing. This technique has since been developed into the single flap approach12 or modified-minimally invasive papilla preservation surgical flap technique.13 Surgical papilla preservation flaps rely not only on good magnification, but also the use of microsurgical instruments (Figure 8).

Figure 7. Diagram schematic to illustrate papilla preservation flap technique. (a, b) Pre-surgical. (c, d) Buccal full-thickness flap with the defect-associated papilla still in place. (e, f) Papilla elevated along with the full-thickness palatal flap. (g, h) Barrier membrane placed following debridement. (i, j) Placement of sutures. The left column depicts the buccal view and the right column the occlusal view.
Figure 8. An example range of microsurgical instruments.

GTR versus EMPs

When comparing the use of EMPs to GTR techniques, both have produced improvements in wound healing clinical parameters.14 However, when investigating healing outcomes of both GTR and EMPs, Sanz and colleagues found that all the GTR cases had complications, whereas of the EMP cases, only 8% had complications.6

Proposed flapless technique using enamel matrix derivatives

Recent work carried out by Graziani and colleagues has suggested that Emdogain used following non-surgical debridement can improve clinical parameters.15 While this improvement in clinical parameters has been suggested to reduce the need for future surgery, there is no histological evidence to quantify the type of healing involved, or suggest that regeneration of periodontal tissues has occurred.15

After appropriate case selection (Table 1), Emdogain is applied to clean root surfaces. A single research study suggests that the use of Emdogain Flapless can improve the effectiveness of the first phase of treatment, leading to the hope that patients will not surgical intervention.16 Graziani's work shows a 32% reduction in the need for follow-up treatment, which includes surgical therapy.14 In addition, there is a suggestion of less pain and a reduction in inflammatory markers, which may improve the speed of recovery.17,18


Indications Contraindications
Adjunct to non-surgical periodontal therapy (initial phase of therapy) Uncontrolled diabetes or other systemic diseases that impact healing potential
Pockets ≤5mm Chronic high-dose steroid therapy
Implants Metabolic bone disease
Support wound healing Radiation or other immunosuppressive therapies
Good oral hygiene Infection or vascular impairment at the site
Minimally Invasive Porcine origin
Avoid surgical procedures Allergies to constituents
Smoker

With no initial surgical intervention needed, the manufacturers suggest this method (Table 2) can be incorporated as part of the wider dental team's day-to-day general practice, allowing them to offer more effective phase 1 care.15 However, this assertion needs to be approached with caution, because there is still limited evidence on outcomes, and the high cost of Emdogain (a single vial of Emdogain Flapless costs £109.39 incl VAT at time of writing) may limit utility when similar outcomes may be achieved with effective non-surgical debridement and optimal patient self-care.


Before Emdogain
1. Root debride and scale Removal of biofilm and plaque
2. Root conditioning Application of PreGel. Pressure and gel dislodges blood from pocket. Leave 2 mins.
3. Rinse Saline/ultrasonic waterjet
4. Haemostasis Can be facilitated by floss packing into the pocket
5. Emdogain FL application Pocket base upwards until excess seen
6. Post-operative instructions Oral health instructions to include interdental brushing. Recall at 2–3-monthly intervals

Instruments

To complement the Emdogain Flapless technique, minimally invasive periodontal instruments are available to facilitate the approach, for example micro-mini curettes. Using minimally invasive instruments helps to decrease unwanted iatrogenic damage and facilitate operator ease during the procedure.13 Additionally, Emdogain Flapless uses a thinner canula delivery system (Figure 9) to aid application into the targeted site.15

Figure 9. Emdogain FL delivery system. Courtesy of Straumann.

Conclusion

With a greater understanding of wound healing within the periodontium, we are now able to offer patients innovative techniques that improve the outcome of the treatment provided. With non-surgical, minimally invasive techniques showing some promise (though significant cost), such techniques may have an increased role in promoting wound healing and improving non-surgical periodontal outcomes.15 Further research will be required to ascertain the mechanism of healing in such flapless techniques.