The enamel matrix derivative (Emdogain) enhances human tongue carcinoma cells gelatinase production, migration and metastasis formation.

Enamel matrix derivative Emdogain (EMD) is widely used in periodontal treatment to regenerate lost connective tissue and to improve the attachment of the teeth. Gelatinases (MMP-2 and -9) have an essential role in the promotion and progression of oral cancer growth and metastasis formation. We studied the effects of EMD on human tongue squamous cell carcinoma (HSC-3) cells in vitro and in vivo. In vitro, EMD (100 microg/ml and 200 microg/ml) remarkably induced the MMP-2 and -9 production from HSC-3 cells analysed by zymography and enzyme-linked immunosorbent assay. EMD also slightly induced the MMP-2 and -9 production from benign human mucosal keratinocytes (HMK). Furthermore, EMD clearly induced the transmigration of HSC-3 cells but had no effect on the HMK migration in transwell assays. The in vitro wound closure of HSC-3 cells was notably accelerated by EMD, whereas it had only minor effect on the wound closure of HMKs. The migration of both cell lines was inhibited by a selective cyclic anti-gelatinolytic peptide CTT-2. EMD had no effect on HSC-3 cell proliferation or apoptosis and only a limited effect on cell attachment to various extracellular matrix components. The in vivo mice experiment revealed that EMD substantially induced HSC-3 xenograft metastasis formation. Our results suggest that the use of EMD for patients with oral mucosal carcinomas or premalignant lesions should be carefully considered, possibly avoided.

Inflammatory external root resorption following surgical treatment for intra-bony defects: a report of two cases involving Emdogain and a review of the literature.

BACKGROUND: Enamel matrix-derived proteins have been shown to regenerate periodontal tissues lost as a result of disease in humans. Emdogain, a commercial preparation of porcine enamel matrix derivative (EMD), has been shown to induce new cementum, periodontal ligament and bone formation in human periodontal defects. Although a number of studies have reported successful outcomes, local adverse effects have so far not been reported in the literature. This case report describes two examples of external inflammatory resorption following surgical root surface debridement and the use of Emdogain. TREATMENT: The treatment in both cases involved raising a full-thickness flap following completion of non-surgical therapy. The granulation tissue from the defect was removed and the root surfaces debrided. Emdogain was applied following the manufacturers' instructions and involved conditioning the root surfaces with Pref-Gel and applying the Emdogain to the defect. The flaps were sutured and the site reviewed regularly. Radiographs were taken before the treatment was undertaken and also at 6 months to assess the healing of the defect. RESULTS: External inflammatory root resorption was observed on the treated teeth 6-24 months after therapy. CONCLUSION: External inflammatory root resorption may be an unusual adverse event following Emdogain treatment.

Two patterns of histologic healing in an intrabony defect following treatment with enamel matrix derivative: a human case report.

Human histologic evidence of periodontal regeneration following treatment of intrabony defects with enamel matrix derivative has yielded inconsistent results in recent case reports. A 46-year-old woman presenting one deep intrabony defect at the distal root of a mandibular first molar scheduled for extraction was selected for enamel matrix derivative therapy. During surgery, a notch was placed at the most apical level of calculus on the experimental root. Nine months postsurgery, a block section including the distal root and surrounding periodontal tissues was obtained and processed in a mesiodistal plane. Histologic analysis demonstrated two different patterns of healing along the proximal and furcal surfaces. Regeneration with new cellular cementum, bone, and periodontal ligament with functional fiber orientation was observed on the distal aspect of the root, whereas the furcal surface healed through ankylosis. This report underlines the biologic variability in wound healing following enamel matrix derivative therapy in periodontal intrabony defects and within the same defect. Host-specific intrinsic and/or extrinsic factors accounting for this variability remain to be investigated.

A multicenter study evaluating the sensitization potential of enamel matrix derivative after treatment of two infrabony defects.

BACKGROUND: Several studies reported some success toward regeneration in infrabony defects using enamel matrix derivative (EMD). Clinically and statistically significant improvements in probing depth reduction, clinical attachment levels, and bone fill have been demonstrated. This multi-center study evaluated the potential for sensitization to EMD in a subgroup of periodontal patients treated at least twice with at least 2 months between treatments. METHODS: Three hundred seventy-six (376) patients in 11 university-based postgraduate periodontics programs and five private practices were selected. Surgeries were performed on infrabony defects. Following reflection of mucoperiosteal flaps and debridement of the root surface and defect, root conditioning (either citric acid pH = 1 or 24% EDTA) was performed and the site was irrigated with sterile saline. Enamel matrix derivative was reconstituted and applied to the exposed root surface and the bony defect. Flaps were sutured and pressure applied for 5 minutes. The second test defect was treated in a similar manner at least 8 weeks after the first surgery. The patient was given a diary card where any subjective adverse events (erythema, swelling, itching, headache, root hypersensitivity, or pain) were recorded at weeks 1 and 2 post-surgery. In addition, objective adverse events (gingival inflammation, ulcers, abscess, cratering, and lesions) were recorded by the investigator on an adverse event form. RESULTS: No clinical adverse reactions to multiple applications of EMD were noted. Of 376 patients, two were referred to a dermatologist for evaluation, but neither had signs indicating any adverse events due to EMD treatment. Instead their reactions were classified as a small local abscess and tinea cruris. The single immunoassay performed (on the patient with a small local abscess) did not demonstrate any EMD-reactive antibodies, neither IgE nor IgG. Other subjective/objective reactions that occurred during this study were of the type that are commonly experienced by patients immediately following periodontal surgery, but were not related to EMD. They included headache, swelling, itching, pain, and root hypersensitivity. CONCLUSIONS: This study demonstrated a lack of clinical adverse reactions following two separate applications of EMD. Any subjective/objective adverse reactions experienced by the patient were typical complications following routine periodontal surgery and were not directly related to the use of enamel matrix derivative.

Treatment of intrabony periodontal defects with enamel matrix derivative: a literature review.

The enamel matrix derivative (EMD) has been recently introduced in the periodontal field to overcome short-comings associated with currently available regenerative techniques. Information accumulated over the past years with application of EMD guided regeneration (EGR) in intrabony periodontal defects allowed a thorough evidence-based retrospective analysis. Clinical data from EMD controlled studies were pooled for meta-analysis and weighted according to the number of treated defects. Clinical attachment gain amounted to 3.2 +/- 0.9 mm (33% of the original attachment level) and probing reduction averaged 4.0 +/- 0.9 mm (50% of the baseline probing depth) for a total of 317 lesions with a mean baseline depth of 5.4 +/- 0.8 mm. Improvements in clinical parameters achieved with EMD were statistically significant in reference to preoperative measurements. However, despite the overall efficacy of EGR therapy, a significant variation in clinical outcomes was observed. Similar therapeutic results were reported in studies where EGR was compared directly to guided tissue regeneration. However, the controlled clinical trials did not have adequate statistical power to firmly support superiority or equivalency between the 2 regenerative therapies. The statistical superiority of EGR over treatment with open flap debridement has been established. Preliminary histologic investigations with surgically created defects and experimental periodontal lesions demonstrated the ability of EGR to induce formation of acellular cementum and promote significant anaplasis of the supporting periodontal tissues. The potential of EMD to encourage periodontal regeneration was also confirmed in human intrabony defects. However, recent human histologic studies have questioned both the consistency of the histologic outcomes and the ability of EGR to predictably stimulate formation of acellular cementum. Identifying clinical modifying parameters and understanding cellular interactions are apparently essential for the development of methodologies to enhance predictability and extent of EGR clinical and histologic results.

Enamel matrix derivative (EMDOGAIN) in the treatment of intrabony periodontal defects.

The aim of the present clinical trial was to compare the long-term effect of EMDOGAIN treatment as an adjunct to modified widman flap (MWF) surgery with the effect of MWF and placebo treatment. The investigation was a placebo-controlled, randomized multicenter trial involving 33 subjects with 34 paired test and control sites. The protocol required 2 interproximal sites, appropriately separated, in the same jaw with probing pocket depths > or = 6 mm and an associated intrabony defect with a depth of > or = 4 mm and a width of > or = 2 mm as measured on a radiograph. Only predominantly 1- and 2-wall defects were included. Clinical attachment gain and radiographic bone gain were used as primary outcome variables. Assessments were made at baseline, 8, 16 and 36 months. Mean values for clinical attachment level gain in test and control sites at 8 months were 2.1 mm and 1.5 mm, respectively; at 16 months, 2.3 mm and 1.7 mm, respectively; and at 36 months 2.2 mm and 1.7 mm, respectively; and the differences were statistically significantly different at each time point (p < 0.01). The radiographic bone level continued to increase over the 36 months at the EMDOGAIN-treated sites, while it remained close to the baseline level at the control sites. The statistically significant (p < 0.001) radiographic bone gain at 36 months of 2.6 mm at EMDOGAIN-treated sites corresponded to 36% gain of initial bone loss or 66% defect fill. The present trial has demonstrated that topical application of EMDOGAIN onto diseased root surfaces associated with intrabony defects during MWF periodontal surgery will promote an increased gain of radiographic bone and clinical attachment compared to control (placebo application) surgery in the same patient. There was no evidence to indicate any clinical adverse effects from application of EMDOGAIN conjunction with periodontal surgery.

Tooth enamel dust as an asthma stimulus. A case report.

A case report of a first-year dental student with asthma, who experienced exacerbation of symptoms and a severe asthmatic crisis in the course of her preclinical dental training, is presented. Dust generated as a result of preparing natural teeth triggered the bronchoconstrictive response. Her subsequent medical and preventive measures are cited. This case identifies, for the first time, enamel dust as an asthma stimulus, thus serving as a precaution to prospective dental students and personnel afflicted with the disease and emphasizing the importance of effective face masks in dental laboratories during dust-generating procedures.