Enamel matrix derivative for alveolar ridge preservation: A randomized controlled trial.

OBJECTIVE: The aims of this clinical trial were to evaluate the radiographic dimensional changes in alveolar ridge and patient-reported outcomes following tooth extraction and alveolar ridge preservation (ARP) using either deproteinized bovine bone mineral (DBBM) with EMD or DBBM alone. METHODS: Participants requiring at least one posterior tooth extraction and ARP were randomly allocated into two treatment groups: ARP using either DBBM with EMD or DBBM alone. Cone-beam computed tomography (CBCT) images were recorded immediately prior to extraction and at 6 months. Changes in alveolar ridge height (ARH) and alveolar ridge width (ARW) at 1, 3, and 5 mm were recorded. RESULTS: A total of 18 participants with 25 preserved sites were evaluated. ARH and ARW changed significantly from baseline to 6 months for both treatment groups but the difference between the groups was not statistically significant over the 6-month follow-up period (ARH: DBBM/EMD 1.26 ± 1.53 mm vs. DBBM 2.26 ± 1.60 mm; ARW-1 DBBM/EMD 1.98 ± 1.80 mm vs. DBBM 2.34 ± 1.89 mm). A significant difference, favoring DBBM with EMD group, was observed in percentage of sites that had less than 1 mm loss in ARH (54.5% sites in DBBM/EMD group vs. 14.3% sites in DBBM alone group). The participants' perception of bruising, bleeding, and pain in the first two postoperative days was significantly in favor of DBBM alone group. CONCLUSIONS: There were no significant differences in radiographic mean measurements of ARH and ARW following ARB with DBBM and EMD or DBBM alone.

Effects of enamel matrix derivative in nonsurgical periodontal therapy on pro-inflammatory profiles, microbial environment and clinical outcome: a randomized clinical trial.

OBJECTIVES: This study aimed to evaluate the impact of enamel matrix derivative (EMD) application following subgingival instrumentation of residual pockets in periodontitis patients on inflammatory host response, microbiological composition, and clinical outcome. METHODS: In this double-blinded randomized controlled trial, a total of 22 patients with generalized periodontitis stage III or IV presenting with ≥ 6 mm probing pocket depth (PPD) at re-evaluation after initial periodontal therapy were included. Participants were randomly allocated at a 1:1 ratio to subgingival instrumentation with (EMD +) or without (EMD-) non-surgical EMD application into the pocket. PPD, clinical attachment level (CAL), bleeding on probing (BoP), plaque index (PI), as well as a panel of pro-inflammatory cytokines and periodontal pathogen count in the gingival crevicular fluid (GCF) of the respective sites were evaluated at baseline (T0) and six months afterwards (T1). RESULTS: Both treatment groups showed a significant PPD reduction (EMD + 1.33 ± 1.15 mm, p < 0.001; EMD- 1.32 ± 1.01 mm, p < 0.001) as well as CAL gain (EMD + 1.13 ± 1.58 mm, p < 0.001; EMD- 0.47 ± 1.06 mm, p = 0.005) from T0 to T1. While no intergroup differences for PPD reduction were observed, CAL gain was higher in EMD + sites compared to EMD- (p = 0.009). No essential effects on cytokine expression as well as bacterial count were detected. CONCLUSIONS: Application of EMD as an adjunct to subgingival instrumentation of residual pockets yielded benefits regarding CAL gain; however, effects on PPD reduction, inflammatory cytokines, and bacterial count were negligible. TRIAL REGISTRATION: ClinicalTrials.gov (NCT04449393), registration date 26/06/2020. CLINICAL RELEVANCE: Based on the obtained results, additional non-surgical EMD application compared to subgingival instrumentation alone showed no clinically relevant effects on treatment outcome and underlying biological mechanisms.

Recession coverage using the modified coronally advanced tunnel and connective tissue graft with or without enamel matrix derivative: 5-year results of a randomised clinical trial.

OBJECTIVES: To evaluate the 5-year results of single and multiple recession type (RT) 1 and 2 (Miller I to III) recessions treated with the modified coronally advanced tunnel (MCAT) and connective tissue graft (CTG) with or without an enamel matrix derivative (EMD). The main outcome variable was the stability of obtained root coverage from 6 months to 5 years. MATERIALS AND METHODS: In 24 patients, both complete and mean root coverage (CRC and MRC) and gain of keratinised tissue (KT) were assessed at 6 months and 5 years after recession coverage by means of MCAT and CTG with or without EMD. Aesthetic outcomes after 5 years were evaluated using the root coverage aesthetic score (RES). RESULTS: At 5 years, 24 patients with a total of 43 recessions were evaluated. Eight patients (57.14%) of the test and 6 (60.0%) of the control group showed complete root coverage. MRC revealed no statistically significant differences between the two groups, with 73.87 ± 26.83% (test) and 75.04 ± 22.06% (control), respectively. KT increased from 1.14 ± 0.57 mm to 3.07 ± 2.27 mm in the test group and from 1.24 ± 0.92 mm to 3.02 ± 1.55 mm in the control group, respectively. CONCLUSION: Treatment of single and multiple RT 1 and 2 recessions by means of MCAT and CTG with or without EMD yielded comparable clinical improvements which could be maintained over a period of 5 years. The additional use of EMD did not influence the clinical outcomes. CLINICAL RELEVANCE: The use of MCAT + CTG yielded successful coverage of single and multiple RT 1 and 2 gingival recessions, while the additional application of EMD did not seem to influence the results.

Enamel Matrix Derivative Suppresses Chemokine Expression in Oral Epithelial Cells.

Epithelial cells in periodontitis patients increasingly express chemokines, suggesting their active involvement in the inflammatory process. Enamel matrix derivative (EMD) is an extract of porcine fetal tooth germs clinically applied to support the regrowth of periodontal tissues. Periodontal regeneration might benefit from the potential anti-inflammatory activity of EMD for epithelial cells. Our aim was, therefore, to set up a bioassay where chemokine expression is initiated in the HSC2 oral squamous carcinoma cell line and then test EMD for its capacity to lower the inflammatory response. To establish the bioassay, HSC2 cells being exposed to TNFα and LPS from E. coli (Escherichia coli) or P. gingivalis (Porphyromonas gingivalis) were subjected to RNAseq. Here, TNFα but not LPS caused a robust increase of chemokines, including CXCL1, CXCL2, CXCL8, CCL5, and CCL20 in HSC2 cells. Polymerase chain reaction confirmed the increased expression of the respective chemokines in cells exposed to TNFα and IL-1ß. Under these conditions, EMD reduced the expression of all chemokines at the transcriptional level and CXCL8 by immunoassay. The TGF-ß receptor type I kinase-inhibitor SB431542 reversed the anti-inflammatory activity. Moreover, EMD-activated TGF-ß-canonical signaling was visualized by phosphorylation of smad3 and nuclear translocation of smad2/3 in HSC2 cells and blocked by SB431542. This observation was confirmed with primary oral epithelial cells where EMD significantly lowered the SB431542-dependent expression of CXCL8. In summary, our findings suggest that TGF-ß signaling mediates the effects of EMD to lower the forced expression of chemokines in oral epithelial cells.

Enamel matrix derivative expedites osteogenic differentiation of BMSCs via Wnt/ß-catenin pathway in high glucose microenvironment.

INTRODUCTION: The influence of enamel matrix derivative (EMD) on proliferation and osteogenic differentiation of bone marrow mesenchymal stem cells (BMSCs) was explored in high glucose (HG) microenvironment with interaction of Wnt/ß-catenin pathway. MATERIALS AND METHODS: Extraction of BMSCs from Sprague-Dawley rats, culture, and identification were manifested. The cells were treated with different concentration of EMD in HG to figure out the most available concentration for proliferation and osteogenic differentiation. Then, observation of cell growth curve and cell cycle changes, and detection of Osterix, runt-related transcription factor 2 (Runx2), COL-I, early osteogenic indexes, Calcium salt deposition, and ß-catenin protein in Wnt/ß-catenin pathway were assured. After adding Wnt/ß-catenin pathway inhibitor (XAV-939) in the cells with osteogenesis induction, detection of binding of ß-catenin to Osterix was clarified. RESULTS: Via identification BMSCs cultured in vitro was qualified. Different concentrations of EMD could accelerate cell proliferation in HG and osteogenesis induction, and 75 µg/mL EMD had the best effect. The HG augmented BMSCs proliferation and the propidium iodide index of flow cytometry cycle was elevated in HG, which were strengthened via the EMD. After BMSCs' osteogenesis induction, Osterix, Runx2, CoL-1, early osteogenic indexes, and calcium salt deposition were reduced, but elevated via EMD. ß-Catenin was the lowest in the HG, but elevated after EMD. After addition of XAV-939, reduction of ß-catenin and the downstream (Osterix and Runx2) were manifested. Detection of binding protein bands was in ß-catenin and Osterix of the HG after EMD treatment. CONCLUSION: EMD may facilitate the osteogenic differentiation of BMSCs via activating the Wnt/ß-catenin pathway in HG.

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.

Combination of enamel matrix derivative and hyaluronic acid inhibits lipopolysaccharide-induced inflammatory response on human epithelial and bone cells.

OBJECTIVES: The aim of this study was to evaluate the in vitro effect of enamel matrix derivative (EMD) and hyaluronic acid (HA) and their synergistic combination on lipopolysaccharides (LPS)-induced inflammation in human keratinocytes and osteoblasts. MATERIAL AND METHODS: Cells were challenged with LPS (1 µg/ml) and cultured in the following treatment groups with EMD (30 mg/ml) and HA (30 mg/ml): LPS, EMD, HA, EMD + HA, EMD + LPS, HA + LPS, and EMD + HA + LPS. Cell viability, inflammatory cytokine expression, and cell migration were determined using colorimetric assay, quantitative real-time polymerase chain reaction (qPCR), and scratch wound healing assay, respectively. RESULTS: Cell viability was decreased when exposed to LPS compared to the controls. Overall, LPS treatment expressed upregulation on inflammatory cytokine tumor necrosis factor alpha (TNF-α), interleukin 1 beta (IL-1ß), and interleukin 6 (IL-6). EMD and HA reduced up to 3.0-fold the cytokine expression caused by LPS (p < 0.05). EMD and HA statistically induced higher migration in osteoblasts and keratinocytes, respectively. Migration was impaired by LPS, whereas it significantly increased after addition of EMD and HA. CONCLUSIONS: EMD and HA are advantageous biomaterials that individually generate strong directional migratory keratinocyte and osteoblast response. Their combination also enhances cell viability, and anti-inflammatory and migratory abilities to promote healing specially under LPS inflammatory stimulus. Future in vivo and animal research is necessary to further characterize the effect of EMD and HA on periodontal regeneration. CLINICAL RELEVANCE: The use of EMD in conjunction with HA resulted in a reduction of inflammation and improvement of tissue healing at wound sites. Both biomaterials combined may potentially improve the effectiveness of bone regeneration in periodontal bone defects, pointing to the potential clinical relevance of both materials in regenerative periodontal surgery.

Modified coronally advanced tunnel technique with enamel matrix derivative in addition to subepithelial connective tissue graft compared with connective tissue graft alone for the treatment of multiple gingival recessions: prognostic parameters for clinical treatment outcomes.

OBJECTIVES: To investigate factors that influence 12-month outcomes after treatment of multiple gingival recessions (GR) with modified coronally advanced tunnel (MCAT) and subepithelial connective tissue graft (SCTG) with enamel matrix derivative (EMD) (tests) or without (controls). MATERIALS AND METHODS: Twenty patients with 150 GR were treated. Logistic regression models were used to identify baseline parameters that could predict 12-month average root coverage (ARC), complete root coverage (CRC), root esthetic coverage score (RES), gain in keratinized tissue width (KTW), and gain in gingival thickness (GT). RESULTS: The likelihood of ARC > 85% increased sevenfold (odds ratio [OR] = 7.33; 95% confidence interval [CI] = 2.43-12.12), of achieving CRC: 21-fold (OR = 21.23; 95% CI = 10.21-45.32), and of gaining RES = 10: tenfold (OR = 10.23; 95% CI = 5.78-32.23) in favor of EMD-treated sites. With each 1-mm2 increase in baseline avascular exposed root surface area (AERSA), the odds of failure (ARC ≤ 85%, not achieving CRC and postoperative GT ≤ 2 mm) increased almost fourfold (OR = 3.56; 95% CI = 1.98-10.19), fourfold (OR = 4.23; 95% CI = 1.11-9.02), and nearly sixfold (OR = 5.76; 95% CI = 2.43-12.87), respectively. The greater the baseline GT, the more likely the chance of achieving CRC (OR = 10.23; 95% CI = 8.37-16.23) and RES = 10 (OR = 5.50; 95% CI = 3.34-16.43). All models exhibited fair to excellent discrimination and satisfactory calibration. CONCLUSIONS: Based on logistic regression, EMD application improved postoperative ARC, CRC and RES; baseline AERSA predicted 12-month ARC, CRC, and GT gain, whereas baseline GT was a predictor of achieving CRC and perfect RES. CLINICAL RELEVANCE: Additional use of EMD, lower baseline AERSA, and greater baseline GT significantly increase the odds of obtaining better outcomes 12 months after MCAT + SCTG technique.

The role of surgical flap design (minimally invasive flap vs. extended flap with papilla preservation) on the healing of intrabony defects treated with an enamel matrix derivative: a 12-month two-center randomized controlled clinical trial.

OBJECTIVES: Minimally invasive flap designs have been introduced to enhance blood clot stability and support wound healing. Limited data appear to suggest, that in intrabony defects, better clinical outcomes can be achieved by means of minimally invasive flap compared to more extended flaps. The aim of this study was to evaluate the healing of intrabony defects treated with either minimally invasive surgical flaps or with modified or simplified papilla preservation techniques in conjunction with the application of an enamel matrix derivative (EMD). MATERIALS AND METHODS: Forty-seven subjects were randomly assigned to either test (N = 23) or control (N = 24) procedures. In the test group, the intrabony defects were accessed by means of either minimally invasive surgical technique (MIST) or modified minimally invasive surgical technique (M-MIST) according to the defect localization while the defects in the control group were treated with either the modified or simplified papilla preservation (MPP) or the simplified papilla preservation technique (SPP). EMD was used as regenerative material in all defects. The following clinical parameters were recorded at baseline and after 12 months: full-mouth plaque score (FMPS), full-mouth bleeding score (FMBS), probing depths (PD), clinical attachment level (CAL), and gingival recession (GR). Early healing index (EHI) score was assessed in both groups 1 week following the surgery. CAL gain was set as primary outcome. RESULTS: After 12 months follow-up, the CAL gain was 4.09 ± 1.68 mm in test group and 3.79 ± 1.67 mm in control group, while the PD reduction was 4.52 ± 1.34 mm and 4.04 ± 1.62 mm for test and control sites. In both groups, a minimal GR increase (0.35 ± 1.11 mm and 0.25 ± 1.03 mm) was noted. No residual PDs ≥ 6 mm were recorded in both groups. CAL gains of 4-5 mm were achieved in 30.4% and in 29.2% of test and control group, respectively. Moreover, CAL gains ≥ 6 mm were recorded in 21.7% of experimental sites and in 20.8% of control sites. No statistically significant differences in any of the evaluated parameters were found between the test and control procedures (P > 0.05). After 1 week post-surgery, a statistically significant difference (P < 0.05) between the groups was found in terms of EHI score. CONCLUSIONS: Within the limits of this pilot RCT, the results have failed to show any differences in the measured parameters following treatment of intrabony defects with EMD, irrespective of the employed surgical technique. CLINICAL RELEVANCE: In intrabony defects, the application of EMD in conjunction with either MIST/M-MIST or M-PPT/SPPT resulted in substantial clinical improvements.

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.

Enamel Matrix Derivative Decreases Pyroptosis-Related Genes in Macrophages.

Background: Pyroptosis is a caspase-dependent catabolic process relevant to periodontal disorders for which inflammation is central to the pathophysiology of the disease. Although enamel matrix derivative (EMD) has been applied to support periodontal regeneration, its capacity to modulate the expression of pyroptosis-related genes remains unknown. Considering EMD has anti-inflammatory properties and pyroptosis is linked to the activation of the inflammasome in chronic periodontitis, the question arises whether EMD could reduce pyroptosis signalling. Methods: To answer this question, primary macrophages obtained from murine bone marrow and RAW 264.7 macrophages were primed with EMD before being challenged by lipopolysaccharide (LPS). Cells were then analysed for pyroptosis-signalling components by gene expression analyses, interleukin-1ß (IL-1ß) immunoassay, and the detection of caspase-1 (CAS1). The release of mitochondrial reactive oxygen species (ROS) was also detected. Results: We report here that EMD, like the inflammasome (NLRP3) and CAS1 specific inhibitors-MCC950 and Ac-YVAD-cmk, respectively-lowered the LPS-induced expression of NLRP3 in primary macrophages (EMD: p = 0.0232; MCC950: p = 0.0426; Ac-YVAD-cmk: p = 0.0317). EMD further reduced the LPS-induced expression of NLRP3 in RAW 264.7 cells (p = 0.0043). There was also a reduction in CAS1 and IL-1ß in RAW 264.7 macrophages on the transcriptional level (p = 0.0598; p = 0.0283; respectively), in IL-1ß protein release (p = 0.0313), and CAS1 activity. Consistently, EMD, like MCC950 and Ac-YVAD-cmk, diminished the ROS release in activated RAW 264.7 cells. In ST2 murine mesenchymal cells, EMD could not be tested because LPS, saliva, and IL-1ß + TNF-α failed to provoke pyroptosis signalling. Conclusion: These findings suggest that EMD is capable of dampening the expression of pyroptosis-related genes in macrophages.

TGF-ß Signalling Mediates the Anti-Inflammatory Activity of Enamel Matrix Derivative In Vitro.

Enamel matrix derivative (EMD) prepared from extracted porcine fetal tooth material can support the regrow of periodontal tissues. Previous findings suggest that EMD has anti-inflammatory properties and TGF-ß activity in vitro. However, the anti-inflammatory activity of EMD is mediated via TGF-ß has not been considered. To this aim, we first established a bioassay to confirm the anti-inflammatory activity of EMD. The bioassay was based on the RAW 264.7 macrophage cell line and proven with primary macrophages where EMD significantly reduced the forced expression of IL-6. We then confirmed the presence of TGF-ß1 in EMD by immunoassay and by provoking the Smad2/3 nuclear translocation in RAW 264.7 macrophages. Next, we took advantage of the TGF-ß receptor type I kinase-inhibitor SB431542 to block the respective signalling pathway. SB431542 reversed the anti-inflammatory activity of EMD and TGF-ß in a bioassay when IL-6 and CXCL2 expression was driven by the LPS stimulation of RAW 264.7 macrophages. This central observation was supported by showing that SB431542 reversed the anti-inflammatory activity of EMD using IL-1ß and TNF-α-stimulated ST2 bone marrow stromal cells. Together, these findings implicate that the TGF-ß activity mediates at least part of the anti-inflammatory activity of EMD in vitro.

Flapless application of enamel matrix derivative in non-surgical periodontal treatment: A systematic review.

BACKGROUND AND OBJECTIVE: To assess the effects of the flapless application of enamel matrix derivative (EMD) in combination with non-surgical periodontal treatment (NSPT) when compared to non-surgical periodontal treatment alone in adult patients. MATERIAL AND METHODS: An electronic literature search was conducted in MEDLINE, Scopus and Cochrane Library up to March 2021 complemented by a manual search. Human longitudinal studies of >5 participants and at least 3 months follow-up were eligible for inclusion in the review. Clinical outcomes were extracted and pooled. Meta-analysis of the included studies was not possible due to methodological differences. RESULTS: A total of 1199 publications were identified and reviewed for eligibility. Nine of them fulfilled the inclusion criteria. Eight studies were randomized clinical trials. The clinical findings of the majority of the included studies demonstrated that the adjunctive use of EMD with NSPT could lead to significantly improved treatment outcomes including higher PPD reduction, more CAL gain, more robust BOP reduction, higher number of sites with PPD < 5 mm and more frequent pocket closure which reduces the need for further periodontal surgical treatment. Limited biological, microbiological and histological findings were reported. Minimal adverse events were observed. CONCLUSION: The flapless application of EMD during NSPT leads to an improved clinical outcome in regards to CAL gain and PPD reduction when compared to conventional treatment alone. The potential effect on the biological and microbiological outcome is unclear.

Flapless application of enamel matrix derivative in periodontal retreatment: A multicentre randomized feasibility trial.

AIM: To investigate the potential benefit of enamel matrix derivative (EMD) as adjunct to re-instrumentation of residual pockets persisting after steps 1 and 2 of periodontal therapy. MATERIAL AND METHODS: 44 adult patients participated in a multicentre feasibility randomized clinical trial with split-mouth design. They had presented at re-evaluation after initial non-surgical periodontal therapy (steps 1 and 2 of periodontal therapy) for generalized periodontitis with at least 2 teeth with residual probing pocket depths (PPD) ≥5 and ≤8 mm, with bleeding on probing (BOP). Two teeth with similar PPD were randomized to receive re-instrumentation either with (test) or without (control) adjunctive flapless administration of EMD. Differences in the changes of PPD and BOP from baseline to 6 and 12 months were analysed, and the frequencies of pocket closure (PPD ≤4 mm and no BOP) compared. RESULTS: For the primary outcome "change of mean PPD after 6 months," a significant additional benefit of 0.79 ± 1.3 mm (p < .0001) could be observed for the test group. At 12 months, this difference could be maintained (0.85 ± 1.1 mm; p < .0001). The frequency of pocket closure in the test group was 69% at 6 and 80% at 12 months and significantly higher than in the control group with 34% and 42%, respectively (p < .01). CONCLUSIONS: The results of the present feasibility study indicate a benefit of adjunctive EMD during non-surgical retreatment (step 3 of periodontal therapy) of residual deep pockets.

Pocket resolution in regenerative treatment of intrabony defects with papilla preservation techniques: A systematic review and meta-analysis of randomized clinical trials.

AIM: To systematically assess the clinical performance of different approaches for periodontal regeneration of intrabony defects in terms of pocket resolution compared to access surgery with papilla preservation techniques (PPTs). MATERIAL AND METHODS: Systematic literature searches were conducted on PubMed, EMBASE, and CENTRAL up to April 2020 to identify RCTs on regenerative treatment [guided tissue regeneration (GTR) or enamel matrix derivative (EMD) with or without biomaterials] of intrabony defects using PPTs. Results were expressed as weighted mean percentages (WMP) or risk ratios of pocket resolution at 12 months (considering both final PD ≤ 3 mm and ≤4 mm). RESULTS: A total of 12 RCTs were included. Based on a final PD ≤ 3 mm or PD ≤ 4 mm, the WMP of pocket resolution was 61.4% and 92.1%, respectively. EMD and GTR obtained comparable results. Pairwise meta-analysis identified a greater probability of achieving pocket resolution for GTR compared to PPTs. The number needed to treat for GTR to obtain one extra intrabony defect achieving PD ≤ 3 mm or PD ≤ 4 mm over PPTs was 2 and 4, respectively. CONCLUSION: Regenerative surgery represents a viable approach to obtain final PD ≤ 4 mm in the short-term.

Regenerative periodontal surgery and orthodontic tooth movement in stage IV periodontitis: A retrospective practice-based cohort study.

AIM: Evaluation of the effectiveness of regenerative treatment of intra-bony defects in combination with consecutive orthodontic tooth movements in stage IV periodontitis. MATERIAL AND METHODS: A total of 526 intra-bony defects in 48 patients were analysed after regenerative therapy using collagen-deproteinized bovine bone mineral with or without collagen membrane or enamel matrix derivative followed by orthodontic tooth movement initiated 3 months after surgery. Changes in radiographic bone levels (BL) and probing pocket depths (PPD) were evaluated after 1 year and up to 4 years. RESULTS: Tooth loss amounted to 0.57%. Mean BL gain was 4.67 mm (±2.5 mm) after 1 year and 4.85 mm (±2.55 mm) after up to 4 years. Mean PPD was significantly reduced from 6.00 mm (±2.09 mm) at baseline to 3.45 mm (±1.2 mm) after 1 year, and to 3.12 mm (±1.36 mm) after 2-4 years. Pocket closure (PPD ≤4 mm) was accomplished in 87% of all defects. Adjunctive antibiotic therapy did not show any statistically significant impact on treatment outcomes. CONCLUSIONS: Within the limits of this retrospective study design, the findings suggest that the combination of regenerative treatment and consecutive orthodontic tooth movements resulted in favourable results up to 4 years.

Enamel matrix derivative promotes new bone formation in xenograft assisted maxillary anterior ridge preservation-A randomized controlled clinical trial.

OBJECTIVES: To compare the effectiveness of deproteinized bovine bone mineral with 10% collagen alone (DBBMC) or with enamel matrix derivative (DBBMC-EMD) in ridge preservation. METHODS: 42 maxillary anterior teeth were extracted and received either a DBBMC (control) or DBBMC-EMD (test) treatment protocol. CBCT taken before and 4 months after the extraction procedure was used to measure changes in alveolar ridge width (RW), buccal bone height (BH) and palatal bone height (PH). Bone cores were harvested during implant osteotomy preparation, and the samples processed histomorphometrically to assess the fraction of new bone (%NB), residual graft (%RG) and soft tissue matrix (%STM). RESULTS: Overall, both treatment groups showed significant reductions in mean RW from baseline to 4 months after extraction, but no significant change in either mean BH or PH over this time. When CBCT measurements were analysed according to the initial thickness of the buccal wall (BT < 1 mm vs. BT ≥ 1 mm), significant reductions in all ridge dimensions (RW, BH and PH) were noted in the <1 mm BT group. Histomorphometrically, the DBBMC-EMD test group showed significantly increased new bone formation (%NB): (control = 16.5 ± 6.9% cf.; test = 45.1 ± 8.8%) with less residual graft (%RG): (control = 36.8 ± 8.8% cf.; test = 20.3 ± 7.2%) compared to the DBBMC control group. CONCLUSIONS: Both DBBMC alone and DBBMC-EMD treated sites 4 months after extraction lost RW but showed no significant change in BH or PH. Irrespective of treatment, maxillary anterior teeth with thick initial buccal walls (≥1 mm) exhibited less alveolar ridge reduction 4 months after treatment. The addition of EMD to DBBMC resulted in more new bone formation in the test group.

Does enamel matrix derivative application provide additional clinical benefits in the treatment of maxillary Miller class I and II gingival recession? A systematic review and meta-analysis.

OBJECTIVE: This review aimed to evaluate the effects of enamel matrix derivative (EMD) in association with coronally advanced flap (CAF) or CAF + connective tissue graft (CTG) when compared with CAF alone or CAF + CTG for the treatment of gingival recessions (GR) in maxillary teeth. METHODS: Five databases and gray literature were searched up to April 2020, to find randomized clinical trials comparing the clinical effects of CAF + EMD versus CAF alone (first group) or CAF + CTG + EMD versus CAF + CTG (second group) in the treatment of Miller class I and II or Cairo type I gingival recessions (GR). Random effects model of mean differences was used to determine the GR reduction, gain in keratinized tissue width (KTW), and gain in clinical attachment level (CAL). The trial sequential analysis (TSA) was implemented to determine the optimal information size (OIS) and imprecision using the GRADE approach. Bayes factors were calculated as complementary statistical evidence of p value. RESULTS: From 1349 titles identified, 9 trials representing 336 GR were included. The meta-analysis showed a statistically significant difference for GR reduction and CAL gain in favor CAF + EMD (p ≤ 0.05). The additional effect of EMD showed a statistically significant difference in GR reduction in favor CAF + CTG + EMD (p ≤ 0.05). The differences in KTW gain proved to be not statistically significant in both comparison groups. The OIS were not met among meta-analyses. Evidence certainty according the GRADE approach proved to be moderate for GR reduction and gain in CAL, but very low for gain in KTW. CONCLUSION: The adjunctive application of EMD in the treatment of GR in maxillary teeth either with CAF or CTG provided moderate certainty evidence in favor of their use for reduction in GR and gain in CAL at 6 and 12 months. However, their effect on the increase in keratinized tissue band height showed very low evidence certainty for its use. CLINICAL RELEVANCE: To know if EMD could improve the results for root coverage.

Effect of enamel matrix derivative liquid combined with synthetic bone substitute on bone regeneration in a rabbit calvarial model.

OBJECTIVES: This study aimed to verify the effectiveness of EMD-liquid in combination with a synthetic bone substitute in a rabbit calvarial model. MATERIAL AND METHODS: Four 7-mm outer diameter circular slits were created in the calvaria of 10 New Zealand white rabbits, and polycarbonate cylinders were inserted into the slits. Two experimental groups were established: (1) EMD-liquid + bone substitute (Osteon III®; biphasic calcium phosphate (BCP), ß-TCP/HA = 40:60) and (2) saline + bone substitute (Osteon III®; BCP). The cylinders were filled with saturated graft materials and covered with polycarbonate caps. Micro-CT and histomorphometric evaluation were conducted. RESULTS: In the histomorphometric analysis, new bone formation was significantly higher in the bone substitute (BS) + EMD-liquid group than in the BS only group at both 5 and 10 weeks (p < 0.01). There were statistically significant differences in the material area between the bone substitute and bone substitute + EMD-liquid groups at only 5 weeks (p < 0.05). The BS + EMD-liquid group demonstrated reduced material area to a greater extent. In micro-CT analysis, the BS + EMD-liquid group (27.04 ± 8.06 at 5 weeks, 28.49 ± 9.22 at 10 weeks) showed a significantly higher percentage of mineralized tissue volume at both 5 and 10 weeks (p < 0.05) than the BS only group. CONCLUSION: EMD-liquid enhances new bone formation when combined with BCP bone substitute in an animal model. Moreover, the EMD-liquid + BS has significantly lesser material area than BS alone, indicating accelerated graft degradation. Further studies on types of graft materials are required to verify the effect of EMD-liquid and to optimize its regenerative potential. CLINICAL RELEVANCE: This study suggests that EMD-liquid may have beneficial effect on bone regeneration with synthetic bone substitute.

Healing of intrabony defects following regenerative surgery by means of single-flap approach in conjunction with either hyaluronic acid or an enamel matrix derivative: a 24-month randomized controlled clinical trial.

OBJECTIVES: The aim of this randomized controlled clinical trial was to compare the clinical outcomes obtained in intrabony defects following regenerative periodontal surgery using the single-flap approach (SFA) in conjunction with either hyaluronic acid (HA) or enamel matrix derivative (EMD). MATERIALS AND METHODS: Thirty-two intrabony defects in 32 healthy subjects were randomly assigned: HA (test group) or EMD (control group). Clinical attachment level (CAL), probing depth (PD), gingival recession (REC), and bleeding on probing (BOP) were recorded at baseline,12, 18, and 24 months after surgery. RESULTS: At 24 months, both treatments resulted in statistically significant clinical improvements evidenced by PD-reduction and CAL-gain (p<0.001). The mean CAL-gain was 2.19±1.11 mm in the test and 2.94±1.12 mm in the control sites (p=0.067). PD-reduction was statistically significantly higher for the control group (4.5±0.97 mm) than the test group (3.31±0.70 mm), (p=0.001). CAL-gain ≤ 3 mm was observed in 87.5% and in 62.5% of the test and control sites, respectively. Test sites showed slightly lower REC values than the control sites. No statistically significant differences were found for BOP between treatments. CONCLUSIONS: The present findings indicate that both treatments led to statistically significant clinical improvements compared to baseline, although the application of EMD resulted in statistically significantly higher PD-reduction compared to the use of HA. CLINICAL RELEVANCE: The use of HA in conjunction with a SFA resulted in significant PD-reduction and CAL-gain, pointing to the potential clinical relevance of this material in regenerative periodontal surgery.