Effect of an enamel matrix protein derivative (Emdogain®) on ex vivo dental plaque vitality

BACKGROUND: A common clinical observation following surgical periodontal therapy with an enamel matrix derivative (Emdogain) is the improved healing of the soft tissues and the limited inflammation of the operated areas. These clinical observations are empirical and difficult to explain. One of the factors influencing the early wound healing might be a potential antimicrobial effect of Emdogain. AIM: To investigate the effect of Emdogain on the vitality of ex vivo supragingival dental plaque and to compare this effect to that of a standard 0.2% chlorhexidine solution. MATERIALS AND METHODS: 24 patients suffering from adult periodontitis were included in the study. At the beginning of the experiment, all participants were given a professional tooth cleaning. For the following 4 days, they had to refrain from any kind of oral hygiene measures. At day 5, from each of the volunteers, a voluminous plaque biofilm sample was taken with a sterile curette from the vestibular surfaces of the 1st lower molars and divided into 5 equal parts. Each part was mounted with 5 microl of the following solutions: (1) NaCl, (2) enamel matrix derivative dissolved in water (EMD), (3) enamel matrix derivative dissolved in the vehicle (Emdogain), (4) vehicle (propylene glycol alginate, PGA), (5) 0.2% chlorhexidine digluconate (CHX). After a reaction time of 2 min the test solutions were sucked off, and subsequently the biofilm was stained with a fluorescence dye. The vitality of the plaque flora after the treatments was evaluated under the fluorescence microscope (VF%). RESULTS: Plaque samples treated with NaCl showed a mean vitality of 76.8+/-8%. The EMD, Emdogain, PGA and CHX showed VF values of 54.4+/-9.2, 21.4+/-10.6%, 19.6+/-11.6% and 32.3+/-11.8%, respectively. Emdogain, PGA and CHX showed statistically highly significant reductions (p<0.0001) in terms of bacteria vitality when compared to water (negative control) and EMD. Both Emdogain and PGA were found to be statistically significantly different compared to CHX (p<0.001) (positive control). CONCLUSION: The results of this study indicate that Emdogain might have an antibacterial effect on the vitality of the ex vivo supragingival dental plaque flora.     

釉质基质蛋白诱导延迟再植牙牙周愈合的研究

目的：研究应用釉基质蛋白对延迟再植比格犬恒切牙牙周再生的影响。方法：选取3只比格犬的15颗干燥60min的切牙随机分为两组,实验组10颗牙根涂釉基质蛋白;对照组5颗牙根不涂釉基质蛋白,进行再植。8周后处死犬,每隔500μm切取5μm厚的横断切片作组织学观察。结果：与对照组相比,实验组牙再植后能显著地增加牙周膜性愈合的数量（P〈0．001）,并减少替代性吸收（P〈0．001）。结论：釉基质蛋白能对延迟再植牙的牙周愈合有促进作用。     

Effect of enamel matrix derivative (EMDOGAIN®) upon periodontal healing after replantation of permanent incisors in Beagle dogs

Abstract – This study histologically assessed the effect of enamel matrix derivative (EMDOGAIN^®) on periodontal healing in re-implanted teeth in nine Beagle dogs. Incisors in dogs were re-implanted after 15, 30 and 60 min of dry storage with and without the application of EMDOGAIN. The pulps were removed in all teeth. In groups 1 and 2, dog teeth were splinted and the dogs sacrificed after 8 and 12 weeks, respectively. In group 3, dog teeth were not splinted and sacrifice took place after 12 weeks. The histological parameters studied were healed PDL, surface, inflammatory and replacement resorption. Univariable and multivariable analysis of data was performed. Increased incidence of healed PDL was inversely proportional to extraalveolar time. No significant differences were noticed between splinted and non-splinted teeth. The EMDOGAIN group showed a higher incidence of healed PDL, while controls showed a higher incidence of ankylosis. The effect of EMDOGAIN was more pronounced at the 12-week interval.     

Replantation of permanent incisors in children using Emdogain®

Abstract –  The aim of this study was to determine whether application of an enamel matrix protein derivative, Emdogain^® (Biora AB Malmo, Sweden) to the root surface of avulsed permanent incisors would improve postreplantation outcomes in a pediatric population. Between June 1999 and May 2002, 25 avulsed permanent maxillary incisors (22 centrals and three laterals) were treated with Emdogain^® and followed for up to 32 months, mean duration 20.6 months (range: 6.9–32.5 months). Mean patient age at the time of treatment was 12.0 years (range: 7.7–17.6 years) and mean extra-alveolar duration was 185 min (range: 100–300 min). At the end of their follow-up each of the replanted incisors demonstrated radiographic evidence of replacement root resorption and clinical evidence of ankylosis. None of the replanted teeth were affected by inflammatory root resorption and there was no evidence of infection. When compared with the control samples from Barrett and Kenny ( Endod Dent Traumatol 1997;15:269–72.) and Andersson et al. ( Endod Dent Traumatol 1989;5:38–47.) this sample treated with the Emdogain^® protocol demonstrated significantly less root resorption than either of the control samples ( anova , P  < 0.0001). Although the Emdogain^® protocol did not produce periodontal regeneration, it did eliminate inflammatory resorption and infection and led to significantly less root resorption compared with the two historical controls.     

Emdogain® does not prevent progressive root resorption after replantation of avulsed teeth: a clinical study

Abstract –  Emdogain^® has been shown in clinical and experimental studies to promote regeneration of all periodontal tissues: cementum with anchoring fibres, a functional, periodontal ligament and alveolar bone in connection with treatment of marginal periodontitis.
The intention of this study was to analyse whether this regenerative capacity upon the periodontal ligament also worked in a trauma situation where a significant number of PDL cells have been eliminated because of unphysiologic storage or actual damage during avulsion or replantation. Furthermore if ankylosis sites already established because of earlier replantation after avulsion could be surgical removed and application of Emdogain^® could revert the ankylosis stage to a normal PDL situation. The first treatment situation was tested in seven patients with a total of 16 avulsed teeth with varying time of extra oral storage. The teeth were extra-orally endodontically treated and the root and socket covered with Emdogain^® before replantation. All teeth demonstrated subsequent ankylosis, primarily diagnosed by a percussion test. The second treatment situation where an ankylosis was already established constituted of seven patients with a total of 11 teeth because of previous replantation after avulsion. These teeth were all extracted, the ankylosis sites removed and the root and socket treated with Emdogain^®. After 6 months all teeth showed recurrence of ankylosis. It is concluded that Emdogain^® was not able to prevent or cure ankylosis.     

The use of enamel matrix derivative (Emdogain®) for improvement of probing attachment level of the autotransplanted teeth

Abstract –  The enamel matrix derivative (EMD, Emdogain^®) was used for the purpose to obtain the periodontal regeneration on the denuded root-surfaces of the donor teeth in two cases of the immediate tooth-transplantation. The root-surfaces at the cervical portion of the teeth were denuded because of extrusion. The healthy periodontium of each tooth remained at the apical portion of the roots. The denuded root-surfaces were cleansed before extraction. Then, the donor teeth were gently extracted with forceps, administered EMD, and transplanted so that the denuded surfaces were covered by gingival flaps. After the transplantation, the mean probing attachment level (PAL) improved 3.2 mm and 1.5 mm, respectively. The mean probing pocket depth was within normal level. The actual supporting areas of the roots of the transplanted teeth increased and the teeth worked as the abutments of prosthetic bridges.     

Successful treatment of a radicular groove by intentional replantation and Emdogain® therapy

Abstract –  Radicular groove is an anatomical malformation often predisposing to a severe periodontal defect. Treatment of such an anomaly presents a clinical challenge to the operator. Presented is a case of successful treatment of a radicular groove associated with a maxillary lateral incisor in a 15-year-old girl. A combination of endodontic, intentional replantation and Emdogain® therapy was used. At 1-year follow-up, the patient was comfortable and active healing was evident.     

Effects and distribution of the enamel matrix derivative Emdogain® in the periodontal tissues of rat molars transplanted to the abdominal wall

Abstract – The enamel matrix derivative Emdogain^® (EMD) has been found to promote regeneration of lost periodontal tissues. We have studied the effects and distribution of EMD in the periodontal tissues of maxillary rat molars transplanted to a subcutaneous position in the abdominal wall. The molars were transplanted with or without EMD either immediately after extraction or after drying for 30 min. After 2 days, 1, 2 or 4 weeks the rats were killed and the teeth were examined by means of light microscopy and immunohistochemistry with anti-amelogenin antibodies. Teeth transplanted immediately after extraction showed formation of alveolar bone separated from the dental roots by a periodontal space, regardless of the use of EMD. Among the teeth that were transplanted with EMD after drying for 30 min, new alveolar bone was formed in five out of eight teeth after 2 and 4 weeks. None of the teeth that were dried for 30 min and transplanted without EMD showed alveolar bone formation. Only one tooth transplanted with EMD showed root resorption after drying, while resorption was noted in all teeth transplanted without EMD. All teeth that were transplanted with EMD and none of the teeth that were transplanted without EMD showed an immunohistochemical reaction for amelogenin. After 2 days, amelogenin was precipitated on all surfaces exposed at the transplantation procedure. Later, the immunoreactive material was redistributed to cells at the root surface, where it was still demonstrable after 4 weeks. In conclusion, EMD is accumulated in cells at the root surface and promotes regeneration of the periodontal tissues of the transplanted teeth. It also seems to promote healing of root resorption.     

A comparative study on the use of Bio-Oss® and enamel matrix derivative (Emdogain®) in the treatment of periodontal bone defects

The aim of the study was to evaluate the clinical and radiographic outcome following two different techniques of periodontal bone defects treatment. The study included 24 generally healthy subjects with advanced periodontitis. The patients were divided into two equal groups, according to the method applied. In the first group, a bovine-derived hydroxyapatite xenograft (Bio-Oss) combined with a resorbable collagen membrane (Bio-Gide) was used. The other group was treated with enamel matrix derivative (Emdogain). Clinical and radiographic examinations were performed prior to and 1 yr after surgery. The following parameters were evaluated: plaque index, gingival index, probing pocket depth, clinical attachment level, gingival recession, radiographic defect depth, and defect width. All clinical and radiographic parameters (except plaque index and gingival recession) were significantly reduced after treatment in both groups. No differences were revealed between the two groups of patients in examined parameters after treatment. The results demonstrated that the treatment of periodontal bone defects with both techniques leads to similar and significant improvements in clinical and radiographic parameters.     

Comparison of ready-to-use EMDOGAIN®-gel and EMDOGAIN® in patients with chronic adult periodontitis

OBJECTIVES: The aim of this multicenter trial was to compare the clinical and radiographical outcome of a ready-to-use Emdogain-gel (test) with the marketed Emdogain (control). METHODS: Subjects with bilateral infrabony defects > or =4 mm deep and > or =2 mm wide according to radiographs were selected. 88 subjects with probing pocket depth (PPD) > or =6 mm > or =1 month after supervised oral hygiene and scaling participated. At baseline plaque index, bleeding on probing, PPD and probing attachment level were recorded and reproducible radiographs for computer-based bone level measurements were taken. In each subject, 1 tooth was randomly treated with the test and 1 tooth with the control gel. Examinations were repeated 8 and 16 months post-operatively. RESULTS: After 16 months, the mean test PPD was 4.1 mm and the mean control PPD 4.2 mm. The mean gain of attachment was 2.7 mm for test and 2.9 mm for the control sites, and the radiographic measurements demonstrated a mean gain of 1 mm for both test and control sites. CONCLUSION: This series of cases demonstrated a statistically significant reduction of pocket depths and gain of attachment and bone after 8 and 16 months with no difference between the 2 preparations.     

电子探针微量分析法对酸性氟磷酸盐作用乳牙釉质的实验研究

目的:运用电子探针微量分析(electron probe microanalysiser,EPMA)中的面、线分析法研究酸性氟磷酸盐(acidulated phosphate fluaide,APF)作用乳牙釉质前后,乳牙釉质表层氟、钙、磷3种元素含量的分布和变化。方法:将1个下颌第二乳磨牙一分为二,近中和远中分别浸入到APF溶液和去离子水中12h,取出后分别对其窝沟釉质表层进行面、线分析,观察氟、钙、磷的含量分布和变化。结果:APF作用乳磨牙后,釉质表层约20μm深度内氟含量明显增加,最表层约10μm的氟含量相对较高,大于20μm深度的氟含量接近正常,有明显氟含量增加的釉质层成条带状分布;釉质表层的钙、磷含量无明显变化。结论:EPMA面分析能清晰显示一定平面区域微量元素氟和矿物元素钙、磷的浓度分布情况,而线分析则能清晰显示一定直线区域3种元素的浓度分布情况,这两种分析法研究乳牙釉质元素含量分布和变化比较直观。     

Clinical safety of enamel matrix derivative (EMDOGAIN®) in the treatment of periodontal defects

Abstract The aim of the present clinical trial was to test tolerability during 2 treatments with EMDOGAIN® in a large number of patients. An open, controlled study design in 10 Swedish specialist clinics was chosen, with a test group of 107 patients treated with EMDOGAIN® in connection with periodontal surgery at 2 surgical test sites per patient. The procedures were performed 2 to 6 weeks apart on one-rooted teeth with at least 4 mm deep intraosseous lesions. A control group of 33 patients underwent flap surgery without EMDOGAIN® at I comparable site. In total 214 test and 33 control surgeries were performed. Serum samples were obtained from test patients for analysis of total and specific antibody levels. 10 of the patients had samples taken before and after the first surgery. 56 other samples were taken after one treatment with EMDOGAIN®, and 63 after 2 treatments. None of the samples, not even from allergy-prone patients after 2 treatments, indicated deviations from established baseline ranges. This indicates that the immunogenic potential of EMDOGAIN® is extremely low when applied in conjunction with periodontal surgery. Comparison between the test and control groups demonstrated the same type and frequency of post-surgical experiences, i.e., reactions caused by the surgical procedure itself. Clinical probing and radiographic evaluation was performed at baseline and 8 months postsurgery. About half of the patients (44 test and 21 control) were also evaluated after 3 years. There was a significant difference between the test and control results at 8 months post surgery. and this difference had increased further at the 3 year follow-up. The 2.5–3 mm increase in attachment and bone level after treatment with EMDOGAIN® was of the same magnitude as seen in the studies with split-mouth design aiming for lest of effectiveness of EMDOGAIN®.     

Effect of GBR in combination with deproteinized bovine bone mineral and/or enamel matrix proteins on the healing of critical-size defects

OBJECTIVES: To evaluate the effect of guided bone regeneration (GBR) in combination with or without deproteinized bovine bone mineral (DBBM) and/or an enamel matrix derivative (EMD) on the healing of critical-size calvarial defects. MATERIAL AND METHODS: Forty rats were used. In all animals, a standardized critical-size calvarial defect was created surgically. The animals were randomly allocated into 4 groups of 10 animals each. Group A: One calvarial defect was left untreated, while the galeal and the cerebral aspect of the contralateral defect were covered with a bioresorbable membrane (GBR). Group B: One calvarial defect was filled with EMD, while the contralateral defect was treated with GBR and EMD. Group C: One defect was filled with DBBM, while the contralateral defect was treated with combination of GBR and DBBM. Group D: One defect was filled with DBBM combined with EMD, while the contralateral defect was treated with combination of GBR, DBBM and EMD. The healing period was 4 months. Five specimens from each group were macerated and the length, the width and the vertical dimension (thickness) of the remaining defect were evaluated by a stereomicroscope. The remaining specimens in each group were analyzed histologically. RESULTS: The defects of the macerated specimens that were left untreated or were treated only by EMD, DBBM and combination of EMD and DBBM did not present predictably complete healing of the defects. All the defects where GBR was applied alone or combined with DBBM and/or EMD presented always complete healing (P<0.05). The combined use of GBR with EMD and/or DBBM did not offer any significant advantage above GBR alone in terms of healing of the length and the width of the defect. However, the vertical dimension of the defect was significantly higher (P<0.05) in the GBR-treated specimens of Groups C and D. The histological analysis supported these findings. CONCLUSION: The predictability of bone formation in critical-size defects depends mainly on the presence or absence of barrier membranes (GBR). The combined use with deproteinized bovine bone mineral and/or enamel matrix proteins did not significantly enhance the potential for complete healing provided by the GBR procedure.     

Effect of enamel matrix proteins (Emdogain') on healing after re-implantation of "periodontally compromised" roots. An experimental study in the dog

OBJECTIVE: The present experiment was performed to assess whether Emdogain applied on the root surface of extracted teeth or teeth previously exposed to root planning can protect the tooth from ankylosis following re-implantation. MATERIAL AND METHODS: The experiment included two groups of dogs, including five animals each. The root canals of all mandibular third premolars (3 P 3) were reamed and filled with gutta-percha. A crestal incision was placed from the area of the second to the fourth premolar. Buccal and lingual full thickness flaps were elevated. With the use of a fissure bur, the crown and furcation area of 3 P 3 were severed in an apico-coronal cut. The distal and mesial tooth segments were luxated with an elevator and extracted with forceps. Group A: The mesial and distal segments of 3 P 3 were air dried on a glass surface for 60 min. The roots from the right side were conditioned and exposed to Emdogain application. The roots from the left side received the same treatment with the exception of Emdogain application. The mesial and distal tooth segments were re-implanted and the crown portions were severed with a horizontal cut and removed. The buccal and lingual flaps were mobilized and sutured to obtain complete coverage of the submerged roots. Group B: A notch was prepared in each root, 4-5 mm apical of the cemento-enamel junction. The area of the root that was located coronal to the notch was scaled and planned. The roots in the right side of the mandible were treated with Emdogain, while the roots in the left side served as controls. After 6 months of healing, the dogs were killed and blocks containing one root with surrounding tissues were harvested, and prepared for histological examination, which also included morphometric assessments. Thus, the proportions of the roots that exhibited signs of (i) replacement (ii) inflammatory and (iii) surface resorption were calculated. RESULTS AND CONCLUSION: It was demonstrated that healing of a re-implanted root that had been extracted and deprived of vital cementoblasts was characterized by processes that included root resorption, ankylosis and new attachment formation. It was also demonstrated that Emdogain treatment, i.e. conditioning with EDTA and placement of enamel matrix proteins on the detached root surface, failed to interfere with the healing process.