Abstract
Enamel Matrix Derivatives (EMD) is a novel biomaterial that has been discovered in the late ’90 s and has found numerous uses in the field of periodontics. It is mainly used in areas that require natural regeneration and healing. It has found applications in other branches of dentistry, such as; wound healing, regenerative procedures, endodontics, pedodontics, and others. It mainly consists of amelogenins and other proteins such as amelin, enamelin, tufetelin etc. It is known to increase cementogenesis and improve periodontal attachment. The amount of research done on this product is very little and very scattered. The maximum amount of research has been done regarding its use in periodontic surgery and other related procedures since it had been initially discovered as a material that would increase periodontal attachment. Given its various biological properties, it is safe to say that it has the potential to succeed in other branches. Our review, therefore, aims to collect and present the research performed and ongoing research potential regarding EMD products, which are now available in a gel-based form known as Emdogain.
Introduction
Enamel Matrix Proteins are a group of proteins that are secreted by Hertwig’s Epithelial Root Sheath [1]. The fraction extracted from developing porcine teeth is known as Enamel Matrix Derivative [1]. It majorly comprises amelogenins, and other proteins include amelins, enamelin, etc. A therapeutic agent that increases periodontal regeneration after periodontal surgery was approved in the United States in 19962. It is an Enamel Matrix Derivative known as Emdogain (Straumann,Biora AB, Malmo, Sweden) [1, 2]. It is extracted from the developing enamel of porcine origin and majorly consists of amelogenin.It is usually an aqueous solution of propylene glycol alginate. It has been widely used in the field of Periodontics; especially in the treatment of intrabony defects. Its primary clinical function is to stimulate new periodontal attachment, including PDL, Cementum, and Alveolar Bone [2].
Enamel Matrix Derivative (EMD’s); Emdogain has been used for perforation repair, pulpotomy agent for primary teeth, etc. Apart from its general ability to induce periodontal regeneration, it also has other possible applications in other branches such as endodontics, pedodontics,trauma management and others [3].
This review aims to explain Emdogain as a biomaterial in periodontal regenerative procedures and view its various possible applications.
Data search strategy
An electronic search was conducted with the words enamel matrix derivative, Emdogain, Endodontics, Trauma Management, Periodontics, Implantology, Wound Healing, Enamel MAtrix proteins and Regeneration Potential. All the collected records were scrutinized, and the collected information was distributed under the following headings; Histological background Mechanism of action Commercial availability in India Clinical applications Periodontology Implantology Trauma management Endodontics Pedodontics
Histological background
About 20 years ago, Lars Hammarstrom, Sven Lindskog, and Leif Blomoff [4] found that enamel matrix proteins(EMP) could be used as an agent capable of periodontal regeneration. Five years later, it was proven in studies conducted by Lindskog et al [5] and Slavkin et al [6]; that certain EMP’s were deposited on the tooth surface during growth. They could play a possible role in cementogenesis. This finally became the base hypothesis of many clinical studies that proved that Hertwig’s Epithelial Root Sheath cells played a significant role in cementogenesis and periodontal regeneration. The proteins secreted by these cells are known as Enamel Matrix Proteins(EMP). The purified form extracted from porcine teeth is known as Enamel Matrix Derivative(EMD). The term EMD was coined in 1997 [7]. These proteins are known to self-assemble into supramolecular aggregates that form extracellular matrices and function to control the ultrastructural organization of the developing enamel crystals [8]. Amelogenin is the main content of these proteins, and others include, amelin tuftelin, enamelin etc [8].
Mechanism of action
The precise mechanism of action of Emdogain is unknown,but in vitro studies have demonstrated that it influences the migration, attachment, proliferative capacity and biosynthetic activity of PL cells. During odontogenesis,enamel matrix derivatives are replaced by pre-ameloblasts, including amelogenins.The proliferation of periodontal ligament cells is stimulated more quickly than that of fibroblasts and bone cells [2].
Commercial availability in India
In India EMD is available as Emdogain Gel which is a glycol based gel. It is of the Straumman Company of the United States of America.
Clinical applications
Periodontology
Emdogain is used in various periodontal surgeries and procedures. Heijl L, 1997 [9], in his study concluded that topical application of EMDOGAIN onto diseased root surfaces associated with intrabony defects during MWF periodontal surgery promoted an increased gain of radiographic bone and clinical attachment compared to control (placebo application) surgery in the same patient. Sculean et al [10] reported 32 cases in 1999 wherein Emdogain was used to treat intrabony defects and it was seen that the treatment of intrabony periodontal defects with Emdogain may lead to significant improvements of all clinical parameters.In a case reported in 2003 by Abbas et al [11] the clinical procedures and outcomes of the treatment of several gingival recessions were described. Initial gingival recession averaged 4.8 mm, with a mean probing pocket depth of 2.2 mm. At the 12-month follow-up, a mean of 3.5 mm of root coverage was observed. Probing pocket depth-averaged 1.7 mm, indicating a 4-mm gain of clinical attachment (range 3 to 5 mm). Mucogingival surgery combined with the application of Emdogain gel resulted in predictable root coverage and clinical attachment gain while maintaining shallow pockets. A prospective controlled clinical study done in 2005 by Francetti et al. [12]; proved that The use of EMD as an adjunct to periodontal surgery in the treatment of angular defects significantly enhanced the rate and degree of periodontal regeneration. In 2009, an intervention review was performed by Esposito et al [13], where 13 case reports were collected and a meta analysis was performed where it was seen that Probing Attachment Level had improved by 1.1 mm and Pocket Probing Depth had reduced by 0.9 mm on using EMD for one year.
Implantology
Studies on the use of EMD in implantology are far and few. An experimental study was conducted by Miron et al.; using titanium discs. It was seen that Alkaline phosphatase activity was significantly increased on EMD-coated titanium compared with titanium alone. There was a 6 fold increase in levels of mRNA encoding bone sialoprotein and osteocalcin in osteoblasts cultured on EMD-coated titanium surfaces compared with uncoated surfaces. It was concluded that titanium coating with EMD enhanced the proliferation and differentiation of osteoblasts irrespective of the titanium substratum topography [14].
Trauma management and tooth replantation
According to a case reported by Baygin et al.; Emdogain was used to successfully manage a horizontally fractured tooth along with MTA.No pathologies were found, marked healing in the periodontal tissues and ankylosis were found observed in the teeth at the 48-month clinical-radiographic follow-up [15]. In a report by Caglar et al.; it was seen that he used Emdogain in the reimplantation of avulsed teeth. At 1–2–6–12-month follow-up period, the clinical and radiographic appearance of the teeth showed resolution of mobility and no signs of replacement resorption [16].
Endodontics
Emdogain gel has had various applications in the many treatment procedures for endodontics, mainly in procedures requiring regeneration. When compared against products such as MTA and Calcium Hydroxide, its results proved to be inconclusive. Olsson et al [17]; in his study, showed that in the EMD gel-treated teeth, postoperative symptoms were scarcer, and the amount and pattern of hard tissue formation were markedly different and superior to in the teeth treated with calcium hydroxide. Heziami et al [18]; in their analysis, also showed that Emdogain combined with MTA was efficient as a direct pulp capping agent.
Pedodontics
In a study conducted by Sunitha et al.; a comparison was drawn between Formocresol, Pulpotec, MTA, and Emdogain as pulpotomy agents [19]. MTA and Emdogain had similar values, thus proving EMD could at least be as good as MTA. It has also proved to be a successful indirect pulp capping agent, according to Nakamura et al [20].
Discussion
From the above review, it becomes clear that Emdogain has use in Periodontics and other branches. The maximum amount of research and treatment trials have been done in the field of Periodontics and Periodontal Regeneration. It has been proved to be a promising biomaterial to stimulate natural growth and healing. Emdogain with or without additives has been successful histologically by Mohammadi et al [21] and Hezaimi et al [18]. Emdogain used in various other treatment regimes has also succeeded, as seen in the studies described above. Our review has tried to bring together scattered research studies and reports that show Emdogain as a potential biomaterial with multiple functions in multiple branches. Compared with most other biomaterials, Emdogain proves to be at least as good as if not better than most materials considered ‘gold standard. In a systematic review by Rathe in 2009 [22], Guided Tissue Regeneration with and without Emdogain was compared. It was proven by most collected records that Emdogain was a successful adjuvant to GTR. Birang et al [23] proved that Emdogain combined with bone ceramic promoted better bone growth in osseous defects. It has been enlisted as an injectable bio-regenerative material by Haugen et al [24] in his review on injectable biomaterials. In another systematic review conducted by Soares [25] in 2020, EMD was not found to have any significant result in treating Class II furcation defects. Youseff [26] compared the osteogenic, odontogenic, angiogenesis, and cell viability of dental pulp stem cells on using MTA, Calcium Hydroxide, Biodentine and Emdogain. It was seen that Emdogain could replace MTA and Biodentine in terms of healing the pulp. It has a wide role to play in tissue engineering and will be helpful in periodontal regeneration [27].
Conclusion
In this review, we want to conclude that it is possible to consider Emdogain for various branches and their treatment regimes. Since this product is not very well researched and homogenous data is not yet available, it is not easy to zero in on its exact potential. This very reason makes this material more open to research and development.
Conflict of interest
The authors have no conflict of interest to report.