Generalizability of the added benefits of guided tissue regeneration in the treatment of deep intrabony defects. Evaluation in a multi-center randomized controlled clinical trial. Enamel matrix proteins and guided tissue regeneration with titanium-reinforced expanded polytetrafluoroethylene membranes in the treatment of infrabony defects: a comparative controlled clinical trial. The simplified papilla preservation flap in the regenerative treatment of deep intrabony defects: clinical outcomes and postoperative morbidity. Periodontal regeneration of human intrabony defects with bioresorbable membranes. A controlled clinical trial. Guided tissue regeneration procedure with bioresorbable membranes versus conventional flap surgery in the treatment of infrabony periodontal defects. Treatment of deep and shallow intrabony defects. A multicenter randomized controlled clinical trial. Comparison of treatments of infrabony defects with enamel matrix derivative, guided tissue regeneration with a nonresorbable membrane and Widman modified flap. A pilot study. Comparison of 2 clinical techniques for treatment of gingival recession. Treatment of intrabony defects with enamel matrix proteins or barrier membranes: results from a multicenter practice-based clinical trial. Treatment of intrabony defects with enamel matrix proteins and guided tissue regeneration. A prospective controlled clinical study. Root coverage using the coronally positioned flap with or without a subepithelial connective tissue graft. Mucogingival versus guided tissue regeneration procedures in the treatment of deep recession type defects. Root coverage in isolated gingival recessions using autograft versus allograft: a pilot study. Guided tissue regeneration versus coronally repositioned flap in the treatment of recession with double papillae. Coverage of Miller class I and II recession defects using enamel matrix proteins versus coronally advanced flap technique: a 2-year report. Enamel matrix proteins in the regenerative therapy of deep intrabony defects. Evaluation of human recession defects treated with coronally advanced flaps and either enamel matrix derivative or connective tissue. Part 1: Comparison of clinical parameters.
Several studies have shown that GTR therapy of intrabony defects results in significantly better outcomes than access flap alone. Most of the available data, however, have been produced in highly controlled research environments by a small group of investigators. Generalizability of results to different clinicians and different subject populations has not been evaluated so far.
                This parallel group study involved 143 patients recruited in a practice-based research network of 11 offices in 7 countries. It was designed to evaluate: 1) the applicability of the documented added benefits of GTR in the treatment of intrabony defects to different populations, and 2) the generalizability of the expected results to different clinicians. GTR was compared to access flap alone. Defects, one in each patient, were accessed with a previously described papilla preservation flap in both the test and control group. In addition, GTR sites received application of a bioabsorbable poly-D,L-lactide-co-glycolide membrane. A stringent plaque control regimen was enforced in all patients during the 1-year observation period. Outcomes included gains in clinical attachment (CAL) and reductions in probing depth.
                Observed gains in CAL were 2.18 +/- 1.46 mm for access flap and 3.04 +/- 1.64 mm for the GTR-treated group. The treatment-associated difference was statistically significant (P = 0.03) after correcting for both center effect and defect anatomy. Among the various centers, a 1.73 mm difference in CAL gain was observed. This is a clinically relevant amount, which underlines the significance of center variability in the outcome of periodontal surgical procedures. A frequency distribution analysis of the obtained CAL gains indicated that GTR treatment of deep intrabony defects decreased, with respect to the access flap control, the probability of obtaining only a modest attachment gain at 1 year. Conversely, CAL gains of 4 mm or more were observed in more than 40% of GTR-treated defects and in less than 20% of the controls (P < 0.0001).
                These data indicate that GTR therapy of deep intrabony defects performed by different clinicians on various patient populations resulted in both greater amounts and improved predictability of CAL gains than access flap alone. Several studies have documented the clinical efficacy of guided tissue regeneration (GTR) with non-resorbable expanded polytetrafluoroethylene (ePTFE) membranes and enamel matrix proteins (EMP) in the treatment of infrabony defects. The objective of this controlled clinical study was to compare the clinical outcomes of 3 surgical modalities in the treatment of deep interproximal infrabony defects.
                Ninety (90) defects in 90 healthy subjects affected by chronic periodontitis were assigned to 1 of 3 treatment groups by blocking to prognostic variables. The test group was treated with the application of EMP and the simplified papilla preservation (SPP) technique; the second group was treated with titanium-reinforced ePFTE membranes and the SPP technique; and the third group was treated with the SPP technique used as access flap control procedure. No differences were observed in terms of baseline oral hygiene and defect characteristics among the 3 groups, indicating that the blocking approach was effective. A stringent infection control program was adopted for 1 year.
                The 1-year results indicated that: 1) all treatment modalities resulted in clinically significant improvements in clinical attachment levels (CAL) and reduction in probing depth (PD); 2) a statistically significant treatment effect was demonstrated comparing the EMP test, the membrane control, and the flap control groups in terms of CAL gains; 3) both the EMP test and the membrane control groups showed significant CAL gains compared to the flap control group; 4) a statistically significantly greater amount of CAL gain was demonstrated in GTR-treated compared to EMP-treated patients; 5) deeper residual probing depths but smaller increases in gingival recession were demonstrated following EMP therapy; and 6) smoking habits reduced the clinical outcomes of both regenerative procedures.
                The use of a regenerative procedure is indicated in the treatment of deep vertical bony defects since both the regenerative techniques (GTR and EMD) in the present study resulted in clinically and statistically significant improvements in clinical parameters compared to the access flap procedure. The use of EMP can be helpful in esthetically-sensitive sites and in reducing patient morbidity. The aims of the present multi-center, randomized, controlled clinical trial were: 1) to compare the efficacy of the simplified papilla preservation flap with and without a barrier membrane in deep intrabony defects; 2) to evaluate the postoperative morbidity and surgical complications; and 3) to preliminarily test the impact of baseline tooth mobility on clinical outcomes.
                This parallel group, randomized, multi-center, controlled clinical trial involved 112 patients in 8 periodontal practices in 4 countries. A deep intrabony defect in each patient was accessed with the simplified papilla preservation flap. In the test defects, a bioabsorbable membrane was positioned. Patients' experiences with the surgical procedure and postoperative period were evaluated with a questionnaire. Clinical outcomes included clinical attachment level (CAL) and probing depth (PD) changes.
                Complete observations were available for 55 test and 54 control defects. CAL gains at 1 year were 3.5 +/- 2.1 mm in the guided tissue regeneration (GTR) group and 2.6 +/- 1.8 mm in the control group (P = 0.0117). CAL gains > or = 4 mm were observed in 50.9% of GTR sites and 33.3% of control sites. A significant center effect of 2.1 mm was observed (P= 0.01). Initial PD (P= 0.01) and baseline tooth mobility (P= 0.036) were significant covariates. During the procedure, 30.4% of test and 28.6% of controls reported feeling moderate pain, and subjects estimated the hardship of the procedure at 24 +/- 25 visual analog scale (VAS) units in the test group, and at 22 +/- 23 VAS in controls. In terms of the investigated outcomes, differences between test and control groups were not statistically significant. Among the postoperative complications, edema was most prevalent at week 1, and more frequently associated with the test treatment (P= 0.01). In the test group, 53.6% of membranes were exposed at week 3.
                The present study further supports the added benefits of guided tissue regeneration with respect to access flap alone in the treatment of deep intrabony defects, as well as the general efficacy of GTR in different clinical settings. Furthermore, our study indicates a possible influence of baseline tooth mobility on clinical outcomes. The purpose of this controlled clinical trial was to compare the clinical efficacy of 3 treatment modalities in the treatment of deep interproximal intrabony defects. Thirty-six (36) defects in 36 patients were randomly assigned to 1 of 3 treatment groups by blocking to prognostic variables. The test was treated with bioresorbable membranes positioned coronal to the interproximal bone crest; the second group (membrane control) was treated with conventional non-resorbable (ePTFE) barrier membranes applied coronal to the alveolar crest; the third group (flap Control) was treated with an access flap procedure (MWF). No differences were observed in terms of baseline oral hygiene and defect characteristics among the 3 groups, indicating that the blocking approach was effective. A stringent infection control program was enforced for 1 year. The results indicated that: 1) at 1 year all treatment modalities resulted in clinically significant improvements in clinical attachment levels (CAL) and reductions in probing depths; 2) a statistically significant treatment effect (P < 0.0001, ANOVA) was observed comparing the test (4.6 +/- 1.2 mm), the membrane control (5.2 +/- 1.4 mm), and the flap control groups (2.3 +/- 0.8 mm) in terms of CAL gain; 3) differences in terms of CAL gain between the test (bioresorbable) and the membrane control (ePTFE) groups were not statistically significant (P = 0.19, t-test); 4) both the test and the membrane control groups gained significantly more CAL at 1 year than the MWF group (P < 0.0001, t-test). CAL gains > or = 4 mm were observed in 83.3% of cases in both GTR groups, while CAL gains of this magnitude were not detected in the MWF group. We concluded that clinically significant CAL gains can be obtained with GTR procedures using both bioresorbable and non-resorbable membranes. Patients' morbidity, however, was lower in the group treated with bioresorbable membranes. Claims are being made that clinical results of periodontal flap surgery are enhanced when membranes are employed to aid GTR in intrabony pockets. It was the aim of our study to determine whether this assumption was true for a certain bioresorbable membrane (Guidor Matrix Barrier).
                44 intrabony defects were treated in 16 patients. In 21 lesions, conventional flap surgery only was performed, while in 23, similar lesion membranes were placed as an additional treatment task. Results were evaluated over a time span of 12 months.
                In all surgical areas, treatment resulted in significant improvement of parameters such as attachment levels and probing depths, as well as index values for plaque and bleeding on probing. This occurred whether membranes had been used or not, without any significant differences when comparing the collective results of both treatment groups.
                Placement of membranes during periodontal surgery for the enhancement of tissue regeneration in intrabony pockets is often both difficult and time consuming. In the light of our clinical results with resorbable membranes, such extra effort seems hardly warranted. This prospective multicenter intra-individual randomized controlled clinical trial was designed to compare the efficacy of guided tissue regeneration (GTR) with bioresorbable barrier membranes versus access flap surgery, in intrabony defects. 2 similar defects were selected in each of 23 patients and randomly assigned to 1 of the 2 treatments. Surgery consisted of an identical procedure except for the omission of the barrier membrane in the flap control sites. At 1-year, probing pocket depth reductions were 4.3+/-2.3 mm in GTR treated sites and 3.0+/-1.5 mm in the flap control sites (p=0.02, paired t-test). Clinical attachment level (CAL) gains were 3.0+/-1.7 mm in the GTR sites and 1.6+/-1.8 mm in the control sites (p=0.009, paired t-test). A subset analysis, performed according to the initial depth of the intrabony component of the defects (INFRA), indicated that in shallow defects (INFRA < or =3 mm) treated with the access flap alone, CAL gains were 1+/-1.5 mm, while in deep ones (INFRA > or =4 mm) they were consistently greater (1.9+/-1.9 mm). The % CAL gains, calculated as the % of the baseline intrabony component depth, however, were almost identical in the 2 subpopulations (45.8+/-64.7% in shallow and 43.8+/-37.6% in deep defects). Similarly, in the GTR sites, linear CAL gains were greater in deep (3.7+/-1.7 mm) than in shallow defects (2.2+/-1.3 mm), but no differences were observed in terms of % CAL gains (76.7+/-27.7% and 75.8+/-45%, respectively). The frequency distribution of CAL changes expressed as %s of the baseline INFRA indicates that most of the sites treated with GTR (73% in shallow and 92% in deep defects) gained 50% or more CAL. Furthermore, many defects (64% of shallow and 33% of deep defects) reached 100% of CAL gain. The present study demonstrated that: (i) GTR with bioresorbable barrier membranes resulted in a significant added benefit in comparison with access flap alone; (ii) the linear amounts of CAL gains were greater in deep than in shallow defects; (iii) CAL gains expressed as %s of the baseline depths of the intrabony component, were similar in shallow and deep defects; (iii) the regenerative procedure tested in the present study resulted in CAL gains equal to the depth of the intrabony component of the defect in some, but not in most of the instances. The purpose of the present study was to compare the efficacy of 3 different surgical procedures in the treatment of infrabony defects: guided tissue regeneration (GTR) with non-resorbable membranes, Widman modified flap (WMF) and enamel matrix derivative (EMD).
                30 patients with an infrabony component > or = 4 mm were selected. 10 were treated with expanded polytetrafluorethylene (ePTFE (Gore - Tex W. L. Gore and Associates, Flagstaff, AZ, USA)) membranes, 10 with WMF and 10 with enamel matrix derivatives (Emdogain (U Biora AB Malm, Sweden)). The efficacy of each treatment modality was investigated through regression analysis. Probing attachment level (PAL) gain, probing depth (PD) reduction and gingival recession (REC) variation were analyzed.
                Both Emdogain (enamel matrix derivative) and ePTFE treatment show significant better results as compared to the WMF procedure in which there were no significant changes in PAL gain and PD reduction at baseline and 1 year after surgery.
                Results from our analysis suggest that there is no statistically significant difference in PAL gain between GTR and EMD. The clinical outcomes of this pilot study may be of little significance, considering the small number of patients, but it has provided an important base for a controlled clinical trial (with a larger number of patients) which is currently in progress. In early case studies, use of a collagen barrier as a guided tissue regeneration (GTR) material has shown particular promise in procedures aimed at root coverage. The similarities between collagen membrane and subepithelial connective tissue graft (SCTG) have made collagen membrane an attractive and a possible alternative material for root coverage. The purpose of this randomized clinical trial was to compare these 2 techniques, SCTG versus a GTR-based procedure (GTRC), for root coverage/recession treatment.
                Sixteen patients with bilateral Miller's Class I or II (gingival recession > or = 3.0 mm) recession defects were treated either with SCTG or GTRC using a newly designed collagen membrane. Clinical parameters monitored included recession depth (RD), clinical attachment level (CAL), probing depth (PD), width of keratinized gingiva (KG), attached gingiva (AG), and recession width (RW), each measured at the mid-buccal area to the nearest 0.5 mm. Measurements were taken at baseline and 6 months. A standard mucogingival surgical procedure was performed. Data were reported as means +/- SD and were analyzed using the paired t test for univariate analysis and restricted/residual maximal likelihood (REML)-based mixed effect model for multivariate analysis.
                No statistically significant differences were observed in RD, CAL, KG, and AG between test and control groups at either time period. However, SCTG showed significantly more residual PD and more RW gain when compared to GTRC at 6 months. Both treatments resulted in a statistically significant (P < 0.05) reduction of recession defects (2.5 mm and 2.8 mm), gain of CAL (2.8 mm and 2.3 mm), reduction of RW (1.9 mm and 2.7 mm), and increase of KG (0.7 mm and 1.1 mm) and AG (0.7 mm and 0.5 mm) for GTRC and SCTG, respectively, when comparing 6-month data to baseline. Mean root coverage of 73% (collagen membrane) and 84% (subepithelial connective tissue graft) was achieved.
                The 2 techniques are clinically comparable. Use of a modified collagen membrane to attain root coverage may alleviate the need for donor site procurement of connective tissue. This prospective multicenter, randomized, controlled clinical trial compared the clinical outcomes of enamel matrix proteins (EMD) versus placement of a bioabsorbable membrane in conjunction with guided tissue regeneration (GTR).
                Seventy-five patients with advanced chronic periodontitis were recruited in seven centers in three countries. All patients had at least one intrabony defect of > or = 3 mm. Heavy smokers (> or = 20 cigarettes/day) were excluded. The surgical procedures included access for root instrumentation using the simplified papilla preservation flap and either the application of EMD or the placement of a GTR membrane. At baseline and 1 year following the interventions, clinical attachment levels (CAL), probing depths (PD), recession (REC), full-mouth plaque scores, and full-mouth bleeding scores were assessed. A total of 67 patients completed the study.
                At 1 year, the EMD defects gained 3.1 +/- 1.8 mm of CAL, versus 2.5 +/- 1.9 mm for GTR defects. Probing depth reduction was 3.8 +/- 1.5 mm and 3.3 +/- 1.5 mm, respectively. A multivariate analysis indicated that the differences between EMD and GTR treatments were not significant while a center effect and baseline PD significantly influenced CAL gains. No significant differences in terms of frequency distribution of the outcomes were observed. All cases treated with GTR presented at least one surgical complication, mostly membrane exposure, while only 6% of EMD treated sites displayed complications (P < 0.0001).
                The results of this trial failed to demonstrate superiority of one treatment modality over the other. GTR outcomes in this trial were lower than anticipated based on previous evidence. This was attributed to the high prevalence of post-surgical complications in the GTR group. Utilisation of enamel matrix proteins (EMD) and application of the guided tissue regeneration principle (GTR) are treatment modalities which both have been shown to result in periodontal regeneration. However, it is yet unknown whether the combination of EMD and GTR may additionally favor the regeneration process.
                The aim of the present controlled study was to evaluate clinically the treatment effect of EMD, GTR, combination of EMD and GTR, and flap surgery (control) on intrabony defects.
                56 patients each of whom displaying one intrabony defect of a depth of at least 6 mm were randomly treated with one of the treatment modalities. Prior to surgery and at one year after, the following parameters were evaluated by a blinded examiner: Plaque index (PlI), gingival index (GI), bleeding on probing (BOP), probing pocket depth (PPD), gingival recession (GR) and clinical attachment level (CAL). No statistical significant differences between the four groups were observed at baseline for any of the investigated parameters.
                At 1 year after therapy, the sites treated with EMD demonstrated a mean PPD reduction of 4.1 +/- 1.7 mm and a mean CAL gain of 3.4 +/- 1.5 mm (p<0.001). The sites treated with GTR showed a mean PPD reduction of 4.2 +/- 1.9 mm and a mean CAL gain of 3.1 +/- 1.5 mm (p<0.001). The sites treated with the combined treatment showed a mean PPD reduction of 4.3 +/- 1.4 mm and a mean CAL gain of 3.4 +/- 1.1 mm (p<0.001). In the control group, the mean PPD reduction was 3.7 +/- 1.4 mm (p<0.001) and the mean CAL gain measured 1.7 +/- 1.5 mm (p<0.01). All 4 treatments led to statistically significant PPD reduction and CAL gain. All three regenerative treatments led to higher CAL gain than the control treatment (p<0.05). No statistical significant differences in PPD reduction and CAL gain were observed between the three regenerative treatments.
                It may be concluded that (a) all 3 regenerative treatment modalities may lead to higher CAL gain than the control one, and (b) the combined treatment does not seem to improve the outcome of the regenerative procedure. Various surgical techniques have been proposed for treating gingival recession. This randomized clinical trial compared the coronally positioned flap (CPF) alone or in conjunction with a subepithelial connective tissue graft (SCTG) in the treatment of gingival recession.
                Eleven non-smoking subjects with bilateral and comparable Miller Class I recession defects were selected. The defects, at least 3.0 mm deep, were randomly assigned to the test (CPF + SCTG) or control group (CPF alone). Recession depth (RD), probing depth (PD), clinical attachment level (CAL), width of keratinized tissue (KT), and gingival/mucosal thickness (GT) were assessed at baseline and 6 months postoperatively.
                Recession depth was significantly reduced 6 months postoperatively (P<0.05) for both groups. Mean root coverage was 75% and 69% in the test and control groups, respectively. There were no significant differences between the two groups in RD, PD, or CAL, either at baseline or at 6 months postoperatively. However, at 6 months postoperatively, the test group showed a statistically significant increase in KT and GT compared to the control group (P<0.05).
                The results indicate that both surgical approaches are effective in addressing root coverage. However, when an increase in gingival dimensions (keratinized tissue width, gingival/mucosal thickness) is a desired outcome, then the combined technique (CPF + SCTG) should be used. The objective of the study was to compare the clinical efficacy of 3 surgical approaches in the treatment of deep recession type defects. Fifty-four (54) gingival recessions > or = 5 mm were randomly assigned to 1 of the 3 treatment groups by blocking the prognostic variables. The first group was treated with a guided tissue regeneration (GTR) procedure using a bioabsorbable membrane, the second with non-resorbable membrane, and the third with a mucogingival surgical approach consisting of a connective tissue graft combined with a coronally advanced flap (bilaminar technique). No differences, in terms of baseline oral hygiene and defect characteristics, were observed among the 3 groups showing an effective blocking approach. The 1-year results indicated that 1) all treatment approaches resulted in clinically significant root coverage and attachment gain; 2) a statistically significant treatment effect (P = 0.012, ANOVA) was observed comparing the bioabsorbable (4.9+/-0.3 mm), the non-resorbable (4.5+/-0.8 mm), and the bilaminar (5.3+/-0.7 mm) groups, in terms of root coverage; 3) the difference in terms of root coverage between the bilaminar and the non-resorbable membrane groups was statistically significant while differences between the 2 GTR groups or between the bilaminar and the bioabsorbable membrane groups did not reach statistical value; 4) the 95% confidence intervals for the proportions of complete successes showed a similar pattern; 5) no statistical difference was demonstrated in the amount of attachment gain among the 3 groups (P=0.73, ANOVA). A regression model showed that the amount of root coverage was significantly affected by the initial recession depth, the procedure and smoking habits: a poorer root coverage result is expected in case of shallow recession type defects, when either bioabsorbable (P < 0.05) or non-resorbable (P < 0.001) membranes are used instead of a bilaminar technique and if the patient smokes (P < 0.01). It was concluded that the mucogingival bilaminar technique is at least as effective as GTR procedures in the treatment of gingival recession > or = 4 mm and thus recession depth is not the parameter which influences the selection of the surgical procedure. Different surgical techniques have been used to treat gingival recessions. This preliminary study compared clinical findings for the treatment of isolated gingival defects using a coronally positioned flap associated with a subepithelial connective tissue graft or an acellular dermal matrix graft.
                Ten subjects with bilateral and comparable Miller Class I or II defects were selected. The defects were > or =3.0 mm deep and were assigned randomly to the test group, which was treated with a coronally positioned flap associated with an acellular dermal matrix, or to the control group, which was treated with a coronally positioned flap associated with a subepithelial connective tissue graft. Probing depth (PD), clinical attachment level (CAL), gingival recession depth (GRD), and width (KT) and thickness (GT) of the keratinized tissue were assessed at baseline and 6 months after the surgery.
                Mean root coverage was 50% in the test group (representing a gingival margin shift of 2.1 +/- 0.99 mm) and 79.5% in the control group (representing a gingival margin shift of 3.5 +/- 1.20 mm). These results were statistically different on intra- and intergroup comparisons (P <0.05). Between-group comparisons revealed statistically significantly greater gains in CAL, GRD, and GT in the control group (P < or =0.05); no differences were found for PD or KT (P > or =0.05).
                The coronally positioned flap associated with a subepithelial connective tissue graft or an acellular dermal matrix graft was effective in root coverage. However, the coronally positioned flap associated with a connective tissue graft provided a more favorable clinical outcome. More expanded studies are needed to confirm the present findings. Twenty buccogingival recessions (3 mm deep) in twenty patients were selected and divided into two groups. Periodontal parameters were recorded (recession reduction, probing depth, clinical attachment level, and keratinized tissue width), and both groups were treated with regenerative therapy using a resorbable polylactic acid membrane. The test group was treated using the double papilla flap procedure, and the control group was treated using the coronally repositioned flap procedure. The results obtained at a 1-year follow-up were comparable between the test and control groups for recession reduction, probing depth, and clinical attachment level, although the test group obtained a very large amount of keratinized gingiva (+74.7%) compared to the control group. The aim of this study was to evaluate a comparison of the coronally advanced flap procedure with or without the use of enamel matrix proteins in the treatment of recession defects.
                This 2-year study was conducted as a blinded, split-mouth, placebo-controlled, and randomized design. Thirty patients from two dental schools with two paired buccal recession defects were chosen. Surgical recession coverage was performed as the coronally advanced flap technique. One site was additionally treated with derivative (EMD) and the other site with a placebo (propylene glycol alginate [PGA]). A blinded examiner assessed pre- and post-surgical measurements. Measurements comprised the height and width of the gingival recession, height of keratinized tissue, probing attachment level, probing depth, and alveolar bone level.
                Twenty-four months after therapy, both treatment modalities showed significant root coverage and probing attachment gain. The mean gingival recession decreased from 3.6 to 0.8 mm for the EMD-treated sites and from 3.8 to 1.4 mm for the control sites. However, this difference was not statistically significant (P = 0.122). Similarly, all other clinical parameters did not differ significantly in the between-group comparison except for the recession width (P = 0.027) and probing depth (P = 0.046) exhibiting higher reductions in the EMD group. Complete root coverage could be maintained over 2 years in 53% of the EMD versus merely 23% in the control group. A total of 47% of the treated recessions in the control group deteriorated again in the second year after therapy compared to 22% in the EMD group.
                Enamel matrix derivative seems to provide better long-term results. This prospective multicentre randomized controlled clinical trial was designed to compare the clinical outcomes of papilla preservation flap surgery with or without the application of enamel matrix proteins (EMD).
                172 patients with advanced chronic periodontitis were recruited in 12 centers in 7 countries. All patients had at least one intrabony defect of > or =3mm. Heavy smokers (> or =20 cigarettes/day) were excluded. The surgical procedures included access for root instrumentation using either the simplified or the modified papilla preservation flap in order to obtain optimal tissue adaptation and primary closure. After debridement, roots were conditioned for 2 min with a gel containing 24% EDTA. EMD was applied in the test subjects, and omitted in the controls. Postsurgically, a strict plaque control protocol was followed. At baseline and 1 year following the interventions, clinical attachment levels (CAL), pocket probing depths (PPD), recession (REC), full-mouth plaque scores and full-mouth bleeding scores were assessed. A total of 166 patients were available for the 1-year follow-up.
                At baseline, 86 test and 86 control patients presented with similar subject and defect characteristics. On average, the test defects gained 3.1+/-1.5 mm of CAL, while the control defects yielded a significantly lower CAL gain of 2.5+/-1.5 mm. Pocket reduction was also significantly higher in the test group (3.9+/-1.7 mm) when compared to the controls (3.3+/-1.7 mm). A multivariate analysis indicated that the treatment, the clinical centers, cigarette smoking, baseline PPD, and defect corticalisation significantly influenced CAL gains. A frequency distribution analysis of the studied outcomes indicated that EMD increased the predictability of clinically significant results (CAL gains > or =4 mm) and decreased the probability of obtaining negligible or no gains in CAL (CAL gains <2 mm).
                The results of this trial indicated that regenerative periodontal surgery with EMD offers an additional benefit in terms of CAL gains, PPD reductions and predictability of outcomes with respect to papilla preservation flaps alone. Recession defects around teeth have been treated with a variety of surgical techniques. Most of the literature suggests that the subepithelial connective tissue graft has the highest percentage of mean root coverage with the least variability. Previous studies have demonstrated that enamel matrix derivative (EMD) has the ability to improve clinical parameters. The purpose of this study was to compare the clinical efficacy of enamel matrix derivative placed under a coronally advanced flap to subepithelial connective tissue placed under a coronally advanced flap in patients with recession type defects.
                Twenty patients with incisors or premolars presenting with a facial recession of > or = 4 mm in contralateral quadrants of the same jaw were treated; 17 patients completed the study. One tooth in each patient was randomized to receive either a coronally advanced flap with a subepithelial connective tissue graft (control) or a coronally advanced flap with EMD (test). Clinical parameters measured at baseline and at 6, 9, and 12 months included amount of recession; width at the coronal extent of the gingival defect; width of keratinized tissue; probing depth; clinical attachment level; inflammation score; plaque score; plaque index; alveolar bone level; tissue texture and color; and patient perception of pain, bleeding, swelling, and sensitivity.
                Results for both the test and control groups were similar for all measured clinical parameters with the exception of early healing, self-reported discomfort, and the amount of keratinized tissue obtained. The coronally advanced flap with EMD was superior to the subepithelial connective tissue graft with regard to early healing and patient-reported discomfort, whereas the subepithelial connective tissue graft demonstrated greater amount of keratinized tissue during the 12-month evaluation period. However, both the test and control showed a significant increase in the amount of keratinized tissue at 9 and 12 months compared to baseline. No significant difference in the amount of root coverage was found between the test and control groups (n = 19; P = 0.82). On average, a gain of 4.5 mm (range 4 to 8 mm) tissue covering the previously exposed root surfaces was achieved with both treatment groups. The average percentages of root coverage for control and test groups were 93.8% and 95.1%, respectively. One hundred percent root coverage was obtained 89.5% of the time with the coronally advanced flap with EMD and 79% of the time with the subepithelial connective tissue graft.
                Based on the results of this investigation, the addition of EMD to the coronally advanced flap resulted in root coverage similar to the subepithelial connective tissue graft but without the morbidity and potential clinical difficulties associated with the donor site surgery.
GTR has a greater effect on probing measures of periodontal treatment than open flap debridement, including improved attachment gain, reduced pocket depth, less increase in gingival recession and more gain in hard tissue probing at re-entry surgery. However there is marked variability between studies and the clinical relevance of these changes is unknown. As a result, it is difficult to draw general conclusions about the clinical benefit of GTR. Whilst there is evidence that GTR can demonstrate a significant improvement over conventional open flap surgery, the factors affecting outcomes are unclear from the literature and these might include study conduct issues such as bias. Therefore, patients and health professionals need to consider the predictability of the technique compared with other methods of treatment before making final decisions on use. Since trial reports were often incomplete, we recommend that future trials should follow the CONSORT statement both in their conduct and reporting. 
There is therefore little value in future research repeating simple, small efficacy studies. The priority should be to identify factors associated with improved outcomes as well as investigating outcomes relevant to patients. Types of research might include large observational studies to generate hypotheses for testing in clinical trials, qualitative studies on patient-centred outcomes and trials exploring innovative analytic methods such as multilevel modelling. Open flap surgery should remain the control comparison in these studies.