EMD-liquid contributes to tissue thickness gain in soft tissue augmentation using a collagen matrix.

OBJECTIVES: To investigate the function of enamel matrix derivative (EMD)-liquid compared to EMD-gel (original Emdogain® with polyglycolic acid-carrier) in inducing soft tissue regeneration using a rat dorsal model. MATERIAL AND METHODS: Four subcutaneous pouches were created through dorsal skin incisions in 18 female Wistar rats and randomly allocated to the following groups: (1) sterile saline + non-crosslinked collagen matrix (CM), (2) EMD-gel + CM, and (3) EMD-liquid + CM. After 2 and 4 weeks of healing, the specimens were harvested and stained with Goldner's trichrome, hematoxylin and eosin, and were immunohistochemically stained with an anti-CD31 antibody. RESULTS: The EMD-liquid group showed the thickest connective tissue compared to the other groups, with statistical significance both at 2 (p < 0.001) and 4 weeks (p = 0.011 and 0.023, respectively). The number of multinucleated giant cells was not significantly different among the groups for both periods. Moreover, there was a tendency to have more blood vessels over a longer period, and the highest number of blood vessels was observed in the EMD-liquid group at 4 weeks (p = 0.009 and 0036, respectively). CONCLUSION: EMD-liquid-treated CM is advantageous compared to using CM alone or EMD-gel-treated CM, owing to the histomorphometric results that show significantly increased soft tissue thickness and number of blood vessels when EMD-liquid was pre-primed to CM. CLINICAL RELEVANCE: EMD with a liquid carrier may be an appropriate biologic supplement to provide cell-inducing properties to the CM scaffold and is clinically more beneficial for phenotype modification therapy than CM only and EMD-gel-treated CM.

Comparative evaluation of treatment outcome of partial pulpotomy using different agents in permanent teeth-a randomized controlled trial.

AIM: To compare and evaluate the clinical and radiographic performance, post-operative pain, and anti-inflammatory intake after partial pulpotomy (PP) with calcium hydroxide (CH), mineral trioxide aggregate (MTA), Biodentine (BD), and Emdogain (EMD) as pulp capping agents in mature permanent molars with definitive diagnosis of reversible pulpitis. MATERIALS AND METHODS: As part of this prospective, randomized clinical trial with four parallel arms (CTRI Registration No.: CTRI/2020/11/029329 dated 24/11/2020), hundred and ten permanent molars with a clinical diagnosis of reversible pulpitis and normal apical tissues, from patients between the ages of 15 and 45 years, were recruited and randomly assigned to four groups-CH, MTA, BD, and EMD. Operative procedure was performed under local anesthesia and dental dam isolation. After carious pulpal exposure, 2 mm of superficially inflamed coronal pulp tissue was amputated and either of the four pulp capping materials was placed. The outcome assessment was carried out at 1, 3, 6, and 12 month(s) and was categorized as success (asymptomatic patients with PAI score = 1) or failure (symptomatic patients or PAI score > 1). RESULTS: There was a significant difference in post-operative pain and anti-inflammatory medication intake after partial pulpotomy with Emdogain vis-à-vis other three capping agents. No difference in both clinical and radiographic performances was observed among the four capping agents. CONCLUSION: Partial pulpotomy when performed following evidence-based guidelines results in high success rates regardless of capping agent employed. EMD can be considered a valid and suitable pulp capping agent in PP. CLINICAL RELEVANCE: Meticulous examination and removal of superficially inflamed pulp under magnification and complete asepsis lead to successful pulpal healing regardless of capping agent employed.

Regaining enamel color quality using enamel matrix derivative.

This study aimed to demonstrate and compare the accuracy of tooth shade selection due to the remineralized enamel crystal with enamel matrix derivative (EMD) in vitro. Etched enamel slices were immersed in four types of mineralization buffers for 16 h. Sodium fluoride (NaF) was added to final concentrations of 1-100 ppm with the mineralization buffer that demonstrated the highest mineralization efficiency. EMD was added to the mineralization buffer containing NaF to see if it has any remineralization capacities. The remineralized enamel crystal was analyzed by SEM and XRD. The tooth shade was evaluated by CIE L*a*b*. The results showed that, without NaF, plate-like nanocrystals were formed on the enamel surface, but with NaF, needle-like nanocrystals were formed. By adding EMD, a layer of well-compacted hydroxyapatite crystals was successfully precipitated onto the natural enamel surface. No significant differences were observed in the L* value of the mineralization surface pre-etching and after mineralization buffer containing NaF and EMD. A new method has been developed to recover the color quality of enamel, as well as to mineralize the tooth enamel by constructing hydroxyapatite crystals with mineralization buffers containing NaF and EMD on the etched tooth surface.

Comparison of the effectiveness of Ankaferd Blood Stopper® and Emdogain in periodontal regeneration.

OBJECTIVES: The present study was performed to compare the effectiveness of Ankaferd Blood Stopper® (ABS) with enamel matrix derivatives (EMD) for treating fenestration defects in rats. MATERIALS AND METHODS: Forty-eight male Wistar rats were randomly divided into six groups (each n = 8). Fenestration defects were created in all rats, to which ABS, EMD, or saline (S) was then applied. The rats were grouped and sacrificed at one of two different time points, as follows: ABS-10-group, ABS-treatment/sacrifice on day 10; EMD-10-group, EMD-treatment/sacrifice on day 10; S-10-group, S-treatment/sacrifice on day 10; ABS-38-group, ABS-treatment/sacrifice on day 38; EMD-38-group, EMD-treatment/sacrifice on day 38; and S-38-group, S-treatment/sacrifice on day 38. Then, histomorphometric analysis including measurements of new bone area (NBA) and new bone ratio (NBR), and immunohistochemical analysis including the determination of osteopontin (OPN) and type-III-collagen (C-III) expression were performed. RESULTS: The NBA and NBR were significantly higher in the ABS-10-group and EMD-10-group compared to the S-10-group (p < .05), and in the EMD-38-group compared to the S-38-group (p < .05). The levels of C-III and OPN immunoreactivity were significantly higher in the ABS-10-group compared to the S-10-group (p < .017). CONCLUSIONS: The results of this study suggested that ABS can promote early periodontal regeneration, although its efficacy seems to decrease over time.

Gingival recession treatment with enamel matrix derivative associated with coronally advanced flap and subepithelial connective tissue graft: a split-mouth randomized controlled clinical trial with molecular evaluation.

OBJECTIVES: The goal of this study was to evaluate the impact of enamel matrix derivative (EMD) on periodontal healing after root coverage (RC) surgery, involving CAF in combination with SCTG, and to assess the molecular profile, verifying the inflammation level in early stage (1 and 2 weeks). MATERIALS AND METHODS: Thirty-two recessions (RT1) were submitted to periodontal surgery with (test) or without (control) EMD. The clinical parameters analyzed on the day of surgery and 6 months after the surgical procedure were as follows: recession height and width, keratinized tissue height, percentual root coverage, and the gingival thickness of keratinized tissue. Moreover, the main inflammatory biomarkers and growth factors (IL-1ß, IL-6, IL-8, FGF, MIP-1α and ß, PDGF, TNF-α, and VEGF) were evaluated at baseline, 7, and 14 days after procedures. RESULTS: The average root coverage was significantly higher in the test group as compared to the control group (86% vs. 66%, p = 0.008). The test side had significantly lesser final RH compared to the control side (p = 0.01). Also, there was a significant reduction of RW in both groups, with more significant results in the test group. KTH and GT were not significantly different at any time and group. After 14 days, the immunological analysis showed an increase of VEGF (p = 0.03) on the test group compared to the control side. CONCLUSION: The use of EMD in RC surgeries resulted in a significantly higher RC, as well as a significant increase in VEGF expression, suggesting that EMD may contribute to the angiogenic and healing process. CLINICAL RELEVANCE: EMD provided better results in root coverage treatment when associated with CAF and SCTG, beyond a greater releasing of angiogenic growth factor (VEGF), which enhanced the result.

Enamel matrix derivative does not affect osteoclast formation or bone resorption in cultures of mouse bone marrow macrophages or human monocytes.

OBJECTIVE: Enamel matrix derivative (EMD) is widely used under the brand name Emdogain® to promote periodontal regeneration in surgical treatment of periodontitis and peri-implantitis. The molecular mechanisms are unclear, but it has been proposed that EMD has stimulatory effects on the root cementum and periodontal ligament cells. Since dental implants lack these structures, we hypothesized that EMD-induced bone gain involve interactions with osteoclast precursor cells, with consequent inhibitory effect on osteoclast formation and/or activity. The aim was to evaluate this hypothesis. MATERIAL AND METHODS: Primary mouse bone marrow macrophages (BMMs) and human peripheral blood monocytes were cultured in the presence of receptor activator nuclear factor-κB ligand (RANKL) to stimulate osteoclast formation. A purified Emdogain® fraction was added to the cell cultures and the effect on number and size of newly formed osteoclasts were evaluated. In cultures on natural bone slices, bioanalytical methods were used to assay osteoclast number and bone resorption. RESULTS: EMD had a negative effect on osteoclastogenesis in mouse cultures on plastic surface, whereas addition of EMD to osteoclast precursor cells on bone substrate did not affect osteoclast formation or bone resorption. CONCLUSIONS: The results on natural bone matrix contradict a direct effect of EMD on osteoclast precursor cells.

Cold Atmospheric Plasma Promotes Regeneration-Associated Cell Functions of Murine Cementoblasts In Vitro.

The aim of the study was to examine the efficacy of cold atmospheric plasma (CAP) on the mineralization and cell proliferation of murine dental cementoblasts. Cells were treated with CAP and enamel matrix derivates (EMD). Gene expression of alkaline phosphatase (ALP), bone gamma-carboxyglutamate protein (BGLAP), periostin (POSTN), osteopontin (OPN), osterix (OSX), collagen type I alpha 1 chain (COL1A1), dentin matrix acidic phosphoprotein (DMP)1, RUNX family transcription factor (RUNX)2, and marker of proliferation Ki-67 (KI67) was quantified by real-time PCR. Protein expression was analyzed by immunocytochemistry and ELISA. ALP activity was determined by ALP assay. Von Kossa and alizarin red staining were used to display mineralization. Cell viability was analyzed by XTT assay, and morphological characterization was performed by DAPI/phalloidin staining. Cell migration was quantified with an established scratch assay. CAP and EMD upregulated both mRNA and protein synthesis of ALP, POSTN, and OPN. Additionally, DMP1 and COL1A1 were upregulated at both gene and protein levels. In addition to upregulated RUNX2 mRNA levels, treated cells mineralized more intensively. Moreover, CAP treatment resulted in an upregulation of KI67, higher cell viability, and improved cell migration. Our study shows that CAP appears to have stimulatory effects on regeneration-associated cell functions in cementoblasts.

Enamel matrix derivative (Emdogain) in treatment of replanted teeth - a systematic review.

OBJECTIVE: The main purpose of the present systematic review was to evaluate the efficacy of enamel matrix derivative Emdogain in healing of replanted teeth in humans. MATERIALS AND METHODS: This review conducted in adherence to PRISMA standards and was registered in PROSPERO with registration number CRD42017062736. We graded the methodological quality of the studies by means of Cochrane's tool of risk of bias in non-randomized studies - of interventions (ROBINS-I). RESULTS: In total, 65 studies were identified for screening, and five studies were eligible. The uneventful healing of replanted teeth was varied from 20% to 75%. Two controlled trials found Emdogain treatment significantly reduced resorption of replanted teeth and improved the healing of periodontal ligament compared with controls. Two studies showed high recurrent resorption in Emdogain treated teeth. CONCLUSIONS: To conclude, the number of publications that met all inclusion criteria were limited and did not allow for drawing evidence for Emdogain being effective in supporting healing of replanted teeth.

Effects of mineral trioxide aggregate, calcium hydroxide, biodentine and Emdogain on osteogenesis, Odontogenesis, angiogenesis and cell viability of dental pulp stem cells.

BACKGROUND: Vital pulp therapy preserves and maintains the integrity and the health of dental pulp tissue that has been injured by trauma, caries or restorative procedures. The enhancement of cells viability and formation of reparative dentine and new blood vessels are vital determinants of the success of direct pulp capping. Therefore, the aims of this study was to evaluate and compare the in vitro osteogenic, odontogenic and angiogenic effects of mineral trioxide aggregate (MTA), calcium hydroxide [Ca(OH)2], Biodentine and Emdogain on dental pulp stem cells (DPSCs) and examine the effects of the tested materials on cell viability. METHODS: DPSCs were treated with MTA, Ca(OH)2, Biodentine or Emdogain. Untreated cells were used as control. The cell viability was measured by MTT assay on day 3. Real-Time PCR with SYBR green was used to quantify the gene expression levels of osteogenic markers (alkaline phosphatase and osteopontin), odontogenic marker (dentin sialophosphoprotein) and angiogenic factor (vascular endothelial growth factor) on day 7 and day 14. RESULTS: All capping materials showed variable cytotoxicity against DPSCs (77% for Emdogain, 53% for MTA, 26% for Biodentine and 16% for Ca(OH)2 compared to control (P value < 0.0001). Osteopontin (OPN) and dentin sialophosphoprotein (DSPP) gene expression was increased by all four materials. However, alkaline phosphatase (ALP) was upregulated by all materials except Emdogain. Vascular endothelial growth factor (VEGF) expression was upregulated by all four tested materials except Ca(OH)2. CONCLUSIONS: Our results suggest MTA, Biodentine and Emdogain exhibit similar attributes and may score better than Ca(OH)2. Emdogain could be a promising alternative to MTA and Biodentine in enhancing pulp repair capacity following dental pulp injury. However, further future research is required to assess the clinical outcomes and compare it with the in vitro findings.

Cytokine expression in response to root repair agents.

AIM: To evaluate the expression of TNF-α, IL-6, IFN-γ, TGF-ß, IL-4, IL-10, RANKL, RANK and OPG on mouse calvarial bone treated with MTA, Geristore® and Emdogain® . METHODOLOGY: Bone wounds were made on the heads of C57BL/6 mice, breaking the periosteum and the cortical surface of the calvaria. Each repair agent was inserted into sectioned Eppendorf microtubes and placed on the bone wound, and soft tissues were sutured. At 14 and 21 days, animals were sacrificed and the treated region was dissected. The calvaria bone was removed, and RNA was extracted. mRNA expression of the aforementioned cytokines was assessed using real-time PCR. Data were analysed by nonparametric methods, including the Mann-Whitney and Kruskal-Wallis tests (P < 0.05). RESULTS: Following treatment with Emdogain® and MTA, mRNA expression of RANKL, RANK and OPG increased significantly (P < 0.05) between days 14 to 21. Geristore® did not alter the basal expression of these mediators during the same period of evaluation. Whilst treatment with Emdogain® did cause a significant increase in TNF-α mRNA expression between days 14 and 21 (P < 0.05), treatment with MTA did not alter the basal expression of this cytokine at either experimental time point. However, TNF-α mRNA expression was down-regulated significantly at day 21 (P < 0.05) when Geristore® was applied. A significant increase in the mRNA expression of IL-6, TGF-ß, IL-10, IL-4 and IFN-γ was observed with Emdogain® and MTA treatment between days 14 to 21, whereas Geristore® reduced significantly the expression of IL-6, TGF-ß and IL-4 (P < 0.05). CONCLUSION: The clinical indication of these repair agents depends on the root resorption diagnosis. Whilst MTA and Emdogain® induce a pro- and anti-inflammatory response early and late, respectively, Geristore® was not associated with an inflammatory reaction when compared with both repair agents.

Osteogain improves osteoblast adhesion, proliferation and differentiation on a bovine-derived natural bone mineral.

BACKGROUND: The use of enamel matrix derivative (EMD) has been shown to facilitate periodontal regeneration by histologically resulting in formation of cementum, periodontal ligament and bone. Recently, a new liquid carrier system for EMD has been introduced with better physicochemical properties specifically designed for bone graft mixing (Osteogain). The aim of this study was to investigate the combination of Osteogain with a bovine-derived natural bone mineral (NBM) on osteoblast migration, adhesion, proliferation and differentiation. MATERIALS AND METHODS: Undifferentiated mouse ST2 stromal bone marrow cells were seeded onto 1)NBM particles alone or 2)NBM + Osteogain. Samples were compared for cell migration at 8 h, cell adhesion at 4 h, cell proliferation at 1, 3 and 5 days and real-time PCR at 3 and 14 days for genes encoding runt-related transcription factor 2 (Runx2), collagen1alpha2 (COL1a2), alkaline phosphatase (ALP) and osteocalcin (OCN). Furthermore, alizarin red staining was utilized to investigate the mineralization at 14 days. RESULTS: Osteogain significantly upregulated cell adhesion over twofold onto NBM particles and promoted cell proliferation at 3 and 5 days after seeding. Furthermore, the combination of NBM with Osteogain significantly upregulated genes encoding Runx2, ALP, COL1a2 and OCN (from 1.5- to 3-fold) and increased alizarin red staining over 3 fold at 14 days when compared to NBM particles alone. CONCLUSION: Pre-coating Osteogain onto NBM bone grafting particles significantly increased cell adhesion, proliferation and differentiation of osteoblasts in vitro. Future animal studies are now necessary to further investigate the regenerative potential of Osteogain in combination with a bone grafting material prior to clinical use for bone regeneration.

Evaluation of the adjunctive effect of platelet-rich fibrin to enamel matrix derivative in the treatment of intrabony defects. Six-month results of a randomized, split-mouth, controlled clinical study.

AIM: This study aimed to compare the results obtained with enamel matrix derivative (EMD) and EMD + platelet-rich fibrin (PRF) in the treatment of intrabony defects (IBDs) in chronic periodontitis patients. MATERIALS AND METHODS: Using a split-mouth design, 28 paired IBDs were randomly treated either with EMD or with EMD + PRF. Clinical and radiographic measurements including clinical attachment level (CAL), probing depth (PD), gingival recession (GR), defect depth (DD), defect width (DW) and defect angle (DA) were recorded at baseline (BL) and at six months following therapy. RESULTS: BL clinical and radiographic measurements were similar for EMD and EMD + PRF groups. Although postsurgical measurements revealed significant reduction for PD and CAL in both groups, no intergroup difference was detected. When EMD and EMD + PRF groups were compared, defect fill was not also statistically different. CONCLUSIONS: Both therapies resulted in significant clinical improvement in IBD treatment. Addition of PRF did not improve the clinical and radiographic outcomes.

Twenty years of enamel matrix derivative: the past, the present and the future.

BACGROUND: On June 5th, 2015 at Europerio 8, a group of leading experts were gathered to discuss what has now been 20 years of documented evidence supporting the clinical use of enamel matrix derivative (EMD). Original experiments led by Lars Hammarström demonstrated that enamel matrix proteins could serve as key regenerative proteins capable of promoting periodontal regeneration including new cementum, with functionally oriented inserting new periodontal ligament fibres, and new alveolar bone formation. This pioneering work and vision by Lars Hammarström has paved the way to an enormous amount of publications related to its biological basis and clinical use. Twenty years later, it is clear that all these studies have greatly contributed to our understanding of how biologics can act as mediators for periodontal regeneration and have provided additional clinical means to support tissue regeneration of the periodontium. AIMS: This review article aims to: (1) provide the biological background necessary to understand the rational for the use of EMD for periodontal regeneration, (2) present animal and human histological evidence of periodontal regeneration following EMD application, (3) provide clinically relevant indications for the use of EMD and (4) discuss future avenues of research including key early findings leading to the development of Osteogain, a new carrier system for EMD specifically developed with better protein adsorption to bone grafting materials.

Gene array of PDL cells exposed to Osteogain in combination with a bone grafting material.

OBJECTIVES: The aim of the present study was to investigate the effects of Osteogain, a new formulation of enamel matrix derivative (EMD) in combination with a grafting material on a wide variety of genes for cytokines, transcription factors and extracellular matrix proteins involved in osteoblast differentiation. MATERIALS AND METHODS: Primary human periodontal ligament (PDL) cells were seeded on natural bone mineral (NBM) particles coated with Osteogain for 24 h and analyzed for regulated gene expression using a human osteogenesis gene super-array kit. Osteoblast-related genes include those transcribed during bone mineralization, ossification, bone metabolism, cell growth and differentiation as well as gene products representing extracellular matrix molecules, transcription factors and cell adhesion molecules. RESULTS: Osteogain significantly upregulated the expression of over 20 of the 100 genes examined including bone morphogenetic protein 2 (BMP2), TGFß1, fibroblast growth factor (FGF), epidermal growth factor (EGF) and platelet-derived growth factor (PDGF) as well as some of their associated receptors. Osteogain also promoted gene expression of a number of osteoblast differentiation markers including collagen1α2 and alkaline phosphatase as well as cell adhesion molecules including fibronectin and a variety of integrin binding proteins. Interestingly, Osteogain promoted calcitonin receptor 55-fold and also promoted annexin A5 gene expression over 12-fold. CONCLUSION: The present study demonstrates that Osteogain is capable of either upregulating or downregulating the expression of a wide variety of genes including those for growth factors and cytokines when combined with a bone grafting material. CLINICAL RELEVANCE: The results from the present study demonstrate the large and potent effect of addition of Osteogain in combination to a bone grafting material over a wide variety of genes supporting osteogenesis.

Bone grafting material in combination with Osteogain for bone repair: a rat histomorphometric study.

OBJECTIVES: Enamel matrix derivative (EMD) has been successfully used for the regeneration of periodontal tissues including new cementum, periodontal ligament, and alveolar bone. Combination of EMD with bone grafting materials has however generated variable clinical results. Recently, we have demonstrated that a new formulation of EMD in a liquid carrier system (Osteogain®) has improved physicochemical properties for the adsorption of EMD to a bone grafting material. The aim of the present study was to investigate the regenerative potential of Osteogain®, in combination with a bone graft, on new bone formation in a rat femur defect model. MATERIALS AND METHODS: Fifty-four critically sized femur defects (3 mm in diameter) were created bilaterally in 27 rats and treated following the group allocation: (1) drilled unfilled control, (2) a natural bone mineral (NBM), and (3) NBM + Osteogain®. All defects were histologically analyzed at 2, 4, and 8 weeks after surgical intervention. Micro-CT analysis, hematoxylin and eosin (H&E) staining, and Safranin O staining were performed to quantify new bone formation. RESULTS: Significantly more new bone formation was observed in defects treated with NBM + Osteogain® at both 4 and 8 weeks when compared to NBM alone and the control unfilled defects (P < 0.05). Histologically, the formation of more mature mineralized bone with the presence of osteocytes were found more commonly in defects treated with Osteogain® + NBM at 8 weeks post-healing when compared to NBM alone. CONCLUSIONS: The present study demonstrate that Osteogain® in combination with a bone grafting material improves the speed and quality of new bone formation in rat osseous defects. CLINICAL RELEVANCE: Future clinical research are now warranted to fully characterize the benefits of Osteogain®, a new formulation of enamel matrix proteins delivered in liquid formation when used in combination with a bone grafting material.

Enamel matrix derivative improves gingival fibroblast cell behavior cultured on titanium surfaces.

OBJECTIVE: Although an extensive amount of research has demonstrated the positive effects of an enamel matrix derivative (EMD) on soft tissue wound healing around intrabony defects, little information is available describing its effect on peri-implant soft tissues, an area that has recently gained tremendous awareness due to the increasing prevalence of peri-implantitis. The aim of the present study was to assess the role of EMD when gingival fibroblasts were cultured on titanium surface with different surface topographies. METHODS: Human primary gingival fibroblasts were cultured on pickled (PT) and sand-blasted with large grit followed by acid etching (SLA) surfaces and assessed for cell adhesion at 2, 4, and 8 h, cell morphology at 2, 4, 8, and 24 h as well as cell proliferation at 1, 3, and 5 days post-seeding. Furthermore, genes encoding collagen 1a1, vascular endothelial growth factor-A (VEGF-A), and fibronectin were assessed by real-time PCR. Human gingival fibroblasts were also quantified for their ability to synthesize a collagen matrix on the various titanium surfaces with and without EMD by immunofluorescence staining. RESULTS: The results from the present study demonstrate that EMD significantly increased cell spreading at 2, 4, 8, and 24 h on PT surfaces and 4, 8, and 24 h on SLA surfaces. Furthermore, proliferation at 5 days on PT surfaces and 3 and 5 days on SLA surfaces was also increased for groups containing EMD. Real-time PCR results demonstrated that the culture of gingival fibroblasts with EMD significantly increased extracellular matrix synthesis of collagen 1 as well as improved mRNA levels of VEGF-A and fibronectin. Collagen1 immuno-fluorescent staining revealed a significantly higher area of staining for cells seeded on PT + EMD at 7 and 14 days and 14 days for SLA + EMD when compared to control samples. CONCLUSION: The results from the present study favor the use of EMD for colonization of gingival fibroblasts on titanium surfaces by increasing cell growth, spreading, and synthesis of an extracellular matrix. The improvements were primarily irrespective of surface topography. Future animal and human studies are necessary to fully characterize the beneficial effects of incorporating EMD during soft tissue regeneration of implant protocols. CLINICAL RELEVANCE: The use of EMD may speed up the quality of soft tissue integration around dental implants by facilitating gingival cell attachment, proliferation, and matrix synthesis of collagen 1.

Enamel matrix derivative, inflammation and soft tissue wound healing.

Over 15 years have now passed since enamel matrix derivative (EMD) emerged as an agent capable of periodontal regeneration. Following thorough investigation, evidenced-based clinical application is now established for a multitude of clinical settings to promote regeneration of periodontal hard tissues. Despite the large number of studies and review articles written on this topic, no single review has compiled the influence of EMD on tissue inflammation, an area of research that merits substantial attention in periodontology. The aim of the present review was to gather all studies that deal with the effects of EMD on tissue inflammation with particular interest in the cellular mechanisms involved in inflammation and soft tissue wound healing/resolution. The effects of EMD on monocytes, macrophages, lymphocytes, neutrophils, fibroblasts and endothelial cells were investigated for changes in cell behavior as well as release of inflammatory markers, including interleukins, prostaglandins, tumor necrosis factor-α, matrix metalloproteinases and members of the OPG-RANKL pathway. In summary, studies listed in this review have reported that EMD is able to significantly decrease interleukin-1b and RANKL expression, increase prostaglandin E2 and OPG expression, increase proliferation and migration of T lymphocytes, induce monocyte differentiation, increase bacterial and tissue debris clearance, as well as increase fibroplasias and angiogenesis by inducing endothelial cell proliferation, migration and capillary-like sprout formation. The outcomes from the present review article indicate that EMD is able to affect substantially the inflammatory and healing responses and lay the groundwork for future investigation in the field.

Common target genes of palatal and gingival fibroblasts for EMD: the microarray approach.

BACKGROUND AND OBJECTIVE: Connective tissue grafts are frequently applied, together with Emdogain(®) , for root coverage. However, it is unknown whether fibroblasts from the gingiva and from the palate respond similarly to Emdogain. The aim of this study was therefore to evaluate the effect of Emdogain(®) on fibroblasts from palatal and gingival connective tissue using a genome-wide microarray approach. MATERIAL AND METHODS: Human palatal and gingival fibroblasts were exposed to Emdogain(®) and RNA was subjected to microarray analysis followed by gene ontology screening with Database for Annotation, Visualization and Integrated Discovery functional annotation clustering, Kyoto Encyclopedia of Genes and Genomes pathway analysis and the Search Tool for the Retrieval of Interacting Genes/Proteins functional protein association network. Microarray results were confirmed by quantitative RT-PCR analysis. RESULTS: The transcription levels of 106 genes were up-/down-regulated by at least five-fold in both gingival and palatal fibroblasts upon exposure to Emdogain(®) . Gene ontology screening assigned the respective genes into 118 biological processes, six cellular components, eight molecular functions and five pathways. Among the striking patterns observed were the changing expression of ligands targeting the transforming growth factor-beta and gp130 receptor family as well as the transition of mesenchymal epithelial cells. Moreover, Emdogain(®) caused changes in expression of receptors for chemokines, lipids and hormones, and for transcription factors such as SMAD3, peroxisome proliferator-activated receptor gamma and those of the ETS family. CONCLUSION: The present data suggest that Emdogain(®) causes substantial alterations in gene expression, with similar patterns observed in palatal and gingival fibroblasts.

Deproteinized bovine bone in association with guided tissue regeneration or enamel matrix derivatives procedures in aggressive periodontitis patients: a 1-year retrospective study.

OBJECTIVES: To retrospectively evaluate and compare two regenerative periodontal procedures in young individuals with aggressive periodontitis (AgP). METHODS: Thirty-two patients aged 14-25 years (mean ± SD 19.3 ± 5.7) were diagnosed as having AgP with multiple intra-bony defects (IBDs) and treated by one of two regenerative modalities of periodontal therapy: guided tissue regeneration (GTR) using deproteinized bone xenograft (DBX) particles and a resorbable membrane (the GTR group), or an application of enamel matrix derivatives (EMD) combined with DBX (the EMD/DBX group). Periodic monitoring of treated sites included recording of probing depth (PD), clinical attachment level (CAL) and gingival recession. Pre-treatment and 1-year post-operative findings were statistically analysed within and between groups. RESULTS: The PD and CAL values decreased significantly with time, but not those between study groups. The mean pre-treatment and 1-year post-treatment PDs of the IBDs of the GTR group (n = 16; sites = 67) were 8.93 ± 1.14 mm and 3.58 ± 0.50 mm, respectively, and the mean CALs were 9.03 ± 1.03 mm and 4.16 ± 0.53 mm respectively. The mean PDs of the EMD/DBX group (n = 16; sites = 73) were 8.77 ± 1.04 mm and 3.61 ± 0.36 mm, respectively, and the mean CALS were 8.79 ± 1.04 mm and 3.77 ± 0.22 mm respectively (p < 0.001 for all). CONCLUSION: Surgical treatment of AgP patients by either GTR or by application of EMD/DBX yielded similarly successful clinical results at 1-year post-treatment.

Tooth autotransplantation with adjunctive application of enamel matrix derivatives using a digital workflow: A prospective case series.

OBJECTIVES: Digital protocols and bioactive materials may reduce complications and improve tooth autotransplantation (ATT) success and survival rates. This prospective study assesses the performance of a fully digital autotransplantation protocol of close-apex molars with the adjunctive application of Enamel Matrix Derivatives (EMD). METHODS: Twelve adult patients with 13 hopeless molar teeth were replaced with autotransplantation of closed apex third molars. Outcomes, including success and survival rates, clinical, endodontic, radiographic, patient-reported outcome measures (PROMs), and digital image assessments, were conducted over a two-year follow-up period. RESULTS: Survival and success rates were 100% and 91.2%, respectively, with no progressive inflammatory or replacement root resorption (ankylosis) except for one tooth presenting radiographic furcation involvement. A significant probing depth reduction of 2.4 ± 2.58 mm and CAL gains of 2.8 ± 3.03 mm were observed in transplanted teeth compared to the hopeless receptor teeth. Radiographic bone levels remained stable throughout the study period (-0.37 ± 0.66 mm), and digital image assessments showed minimal alveolar ridge width changes (-0.32 to -0.7 mm) and gingival margin changes (-0.95 to -1.27 mm) from baseline to last visit. PROMs indicated very high patient satisfaction. CONCLUSION: The use of a digital ATT protocol with adjunctive use of EMD in closed-apex third molars demonstrated promising short-term high success and survival rates. Additionally, this type of therapy adequately preserves the dimensions of the alveolar ridge in the receptor site. CLINICAL SIGNIFICANCE: This is the first prospective clinical study examining the effect of a digital tooth autotransplantation protocol combined with the application of EMD. It demonstrates that this approach is an effective treatment for replacing hopeless teeth and also validates the digital assessment of ATT alveolar ridge preservation at the recipient site.