Periodontal regeneration of a class II furcation defect utilizing a bioabsorbable barrier in a human. A case study with histology.

This case report describes human histologic data of periodontal regeneration following guided tissue regeneration therapy (GTR) with a bioabsorbable barrier composed of polylactic acid. The tooth that was examined was part of a previously published study of the clinical effects of GTR therapy without the use of bone or bone substitutes on Class II furcation defects. Twenty-five months following the surgical procedure, the tooth was extracted for non-periodontal reasons. During this extraction, the bone within the furcation that was treated in the study was luxated with the tooth. At the completion of the study (month 12), the furcation's vertical probing depth had decreased by 2 mm with a 2 mm gain in clinical attachment. The horizontal furcation measurement decreased by 3 mm. Following extraction, the tooth was prepared for light microscopy and sectioned in the mesial-distal plane. Reference notches were not placed in the tooth at the time of surgery as there were no plans to perform histologic analysis in the study. However, using the buccal root prominences and what we interpreted to be root planing marks on the cementum, we were able to demonstrate that complete periodontal regeneration occurred on the root surface that was exposed to the pocket environment prior to surgery. New alveolar bone, cementum, and periodontal ligament were consistently observed throughout the furcation in the areas that demonstrated clinical attachment gain and a decrease in horizontal probing depth. This case report adds to the accumulating evidence of histologic periodontal regeneration following guided tissue regeneration with bioabsorbable polylactic acid barriers.

Two multi-center studies evaluating locally delivered doxycycline hyclate, placebo control, oral hygiene, and scaling and root planing in the treatment of periodontitis.

BACKGROUND: The clinical efficacy and safety of doxycycline hyclate (8.5% w/w) delivered subgingivally in a biodegradable polymer (DH) was compared to placebo control (VC), oral hygiene (OH), and scaling and root planing (SRP) in 2 multi-center studies. METHODS: Each study entered 411 patients who demonstrated moderate to severe periodontitis. Patients had 2 or more quadrants each with a minimum of 4 qualifying pockets > or =5 mm that bled on probing. At least 2 of the pockets were > or =7 mm. Treatment with DH, VC, OH, or SRP was provided at baseline and again at month 4. Clinical parameters were recorded monthly. RESULTS: DH and SRP resulted in nearly identical clinical changes over time in both studies. Mean 9 month clinical attachment level gain (ALG) was 0.8 mm for the DH group and 0.7 mm for the SRP group in Study 1, and 0.8 mm (DH) and 0.9 mm (SRP) in Study 2. Mean probing depth (PD) reduction was 1.1 mm for the DH group and 0.9 mm for the SRP group in Study 1 and 1.3 mm for both groups in Study 2. Frequency distributions showed an ALG > or =2 mm in 29% of DH sites versus 27% of SRP sites in Study 1 and 31% of DH sites versus 34% of SRP sites in Study 2. PD reductions > or =2 mm were seen in 32% of DH sites versus 31% of SRP sites in Study 1 and 41% of DH sites versus 43% of SRP sites in Study 2. Comparisons between DH, VC, and OH treatment groups showed DH treatment to be statistically superior to VC and OH. Safety data demonstrated a benign safety profile with use of the DH product. CONCLUSIONS: Results of this trial demonstrate that treatment of periodontitis with subgingivally delivered doxycycline in a biodegradable polymer is equally effective as scaling and root planing and superior in effect to placebo control and oral hygiene in reducing the clinical signs of adult periodontitis over a 9-month period. This represents positive changes resulting from the use of subgingivally applied doxycycline as scaling and root planing was not limited regarding time of the procedure or use of local anesthesia.

Rationale for the use of Atridox therapy for managing periodontal patients.

This article reviews the studies that provided the safety and efficacy data essential for the Food and Drug Administration approval of Atridox. These studies detail the clinical effectiveness of Atridox and provide the foundation for an understanding of the use of Atridox in the clinical management of patients with periodontitis. Atridox is a locally delivered, controlled-release system for the administration of high concentrations of doxycycline to the periodontal pocket. Nine-month clinical studies involving more than 800 patients have shown Atridox and scaling and root planing to be superior to placebo and oral hygiene for the efficacy parameters of attachment level, probing depth, and bleeding on probing. The positive clinical effects are consistent throughout a wide range of patients with varied histories of periodontal therapy. The implications of these findings as they relate to clinical practice are briefly addressed.

The pharmacokinetic profile of a biodegradable controlled-release delivery system containing doxycycline compared to systemically delivered doxycycline in gingival crevicular fluid, saliva, and serum.

The primary goal of this study was to characterize the release profile of doxycycline hyclate (8.5% w/w) from a biodegradable controlled-release delivery system (DH) placed in periodontal pockets. Pharmacokinetic data were obtained from gingival crevicular fluid (GCF), saliva, and serum of adult periodontitis patients. These results were compared to those obtained from individuals who received standard oral doses of doxycycline hyclate (200 mg on day 0, then 100 mg/day for 7 days). All participants presented with multiple pockets > or = 5 mm that bled upon probing. At the baseline visit patients receiving local drug delivery had all pockets > or = 5 mm that bled upon probing on one side of the mouth filled with DH. Drug retention was enhanced with 1 of 2 periodontal dressings (non-eugenol [NE] or 2-octyl cyanoacrylate [2-octyl]). Doxycycline concentrations were analyzed with the aid of reverse phase high performance liquid chromatography. GCF saliva, and serum samples were obtained just prior to drug delivery and then at hours 2, 4, 6, 8, 18, 24 and days 2, 3, 5, 7, and 8. GCF and saliva samples were also obtained at days 10, 14, 21, and 28. Thirty two subjects participated in the study; 13 in the NE group, 13 in the 2-octyl group, and 6 in the group taking oral doxycycline. The release of doxycycline in the GCF peaked at 2 hours (1473 microg/ml in the NE group, and 1986 microg/ml in the 2-octyl group). The mean concentration at day 7 was 309 microg/ml for the NE group and 148 microg/ml for the 2-octyl group. Minimal levels of drug were detected in the GCF of the oral doxycycline group with a peak concentration of 2.53 microg/ml at 12 hours. Salivary concentrations for both local delivery groups peaked at hour 2 (4.05 microg/ml for the NE group and 8.78 microg/ml for the 2-octyl group); by the end of day 1 levels were < or = 2 microg/ml. For subjects who took the oral doxycycline, salivary concentrations never exceeded 0.11 microg/ml. Serum concentrations of doxycycline for individuals receiving the local drug delivery never exceeded 0.1 microg/ml. For the oral doxycycline group serum concentrations ranged from 0.91 to 2.26 microg/ml over the 8 days data were collected. The high concentration of drug available at the treated sites coupled with the relatively low levels in the saliva and almost non-existent levels in the serum indicate that this biodegradable controlled-release delivery system displays an appropriate pharmacokinetic profile for the delivery of doxycycline into periodontal pockets.

Comparison of a bioabsorbable GTR barrier to a non-absorbable barrier in treating human class II furcation defects. A multi-center parallel design randomized single-blind trial.

This multi-center single-blind study compared clinical outcomes following guided tissue regeneration (GTR) treating human Class II furcation defects with a new polylactic-acid-based bioabsorbable barrier (test treatment) or a non-absorbable ePTFE barrier (control treatment). Clinical parameters evaluated were change in vertical attachment level (VAL), horizontal attachment level (HAL), probing depth (PD), and gingival margin location (REC). Surgical treatment resulted in clinically and statistically equivalent changes when comparisons were made between test and control treatments. VAL gain was 2.0 mm for test and 1.6 mm for control groups; HAL gain was 2.1 mm for both test and control groups. PD reduction was 2.3 mm for the test group and 2.1 mm for the control group. Test sites experienced an additional 0.3 mm of recession beyond baseline; control sites, 0.5 mm. Within-group comparisons showed that the amount of recession was not significantly different from baseline in the test group. Recession in the control group was significantly different from baseline. All other parameters in both the test and control groups were significantly different from baseline. Evaluation of safety data indicated no significant differences between test and control treatments, although there was a strong trend for the control group to have more postoperative abscess or suppuration than test sites (control = 11; test = 4; P = 0.06).

Periodontal regeneration in naturally occurring Class II furcation defects in beagle dogs after guided tissue regeneration with bioabsorbable barriers.

THE EFFICACY OF A BIOABSORBABLE polylactic acid based barrier was evaluated using naturally occurring buccal Class II furcation defects in beagle dogs. Sixteen furcation sites (8 control and 8 experimental) were treated in 6 adult animals. After full thickness flap reflection, exposed furcations and root surfaces were thoroughly root planed. In experimental sites a customized barrier was formed and fitted to cover the defect. Surgical flaps were replaced slightly coronal to the cemento-enamel junction. Animals were sacrificed at 6 months and specimens processed for histologic evaluation. Histologic and histometric analyses were done using 6 micrograms step serial sections in the buccal-lingual plane, corresponding to the buccal-lingual extent of the furcation. Results were: mean total defect experimental sites 1.92 mm; control sites 1.47 mm. Mean new cementum formation experimental sites 1.36 mm (71% of initial defect); control sites 0.25 mm (17% of initial defect). Mean new bone formation experimental sites 1.42 mm (74% of initial defect); control sites 0.20 mm (14% of initial defect). Mean junctional epithelium formation experimental sites 0.42 mm (22% of initial defect); control sites 1.21 mm (82% of initial defect). Statistical analysis demonstrated significant differences in all healing parameters favoring experimental (barrier-treated) sites. In this model, regeneration (new bone, cementum, and periodontal ligament) of 71% of the original defect in experimental sites and only 14% in control sites demonstrated a response that highly favored use of the barrier.

Multi-center comparative evaluation of subgingivally delivered sanguinarine and doxycycline in the treatment of periodontitis. I. Study design, procedures, and management.

The design and conduct of a 9-month multi-center clinical trial to evaluate the safety and efficacy of subgingivally delivered 5% sanguinarium chloride (SC) and 10% doxycycline hyclate (DH) from a biodegradable drug delivery system in the treatment of adult periodontitis is described. The 3-group randomized study of 180 adults with moderate to severe periodontitis was a modified double-blind parallel design. One group received DH, one group received SC, and the other group received the vehicle control (VC). Patients selected had two quadrants with a minimum of four periodontal pockets > or = 5 mm in depth with two sites > or = 7 mm. All qualifying sites exhibited bleeding on gentle probing. Qualifying sites were treated at baseline and again at 4 months. Clinical response was assessed by measuring attachment level, probing depth, and bleeding on probing at monthly examinations at qualifying sites and the entire dentition. The plaque index was measured monthly to verify oral hygiene status. The parallel design afforded the opportunity to distinguish between treatment effectiveness of SC, DH, and VC independent of possible crossover effects. Also the effectiveness of oral hygiene in untreated sites of the mouth could be evaluated. Finally, treatment effects in moderate (5 to 6 mm) and deep (> or = 7 mm) pockets in both treated and untreated sites could be compared. The design was capable of simulating a periodontal practice maintenance program and assessing the response according to maintenance and treatment history. Study management procedures that emphasized center examiner and therapist training and adherence to protocol and procedures to reduce variability are described.

Multi-center comparative evaluation of subgingivally delivered sanguinarine and doxycycline in the treatment of periodontitis. II. Clinical results.

The clinical safety and effectiveness of a subgingivally delivered biodegradable drug delivery system containing either 10% doxycycline hyclate (DH), 5% sanguinarium chloride (SC) or no agent (VC) was evaluated in a 9-month multi-center trial. The study was a randomized parallel design with 180 patients who demonstrated moderate to severe periodontitis. All patients had at least two quadrants with a minimum of four qualifying pockets > or = 5 mm that bled on probing. Two of the qualifying pockets were required to be > or = 7 mm. At baseline and at 4 months all qualified sites were treated with the test article administered via syringe. Probing depth reduction (PDR), attachment level gain (ALG), bleeding on probing reduction (BOP), and plaque index were determined monthly. Analysis of efficacy data from the 173 efficacy-evaluable patients indicated that all treatments gave significant positive clinical changes from baseline at all subsequent timepoints. DH was superior to SC and VC in PDR at all timepoints (P < or = 0.01 to 0.001) with a maximum reduction of 2.0 mm at 5 months. For ALG, DH was superior to VC at months 2, 3, 4, 5, 6, 8, and 9 (P < or = 0.04 to 0.002) and superior to SC at months 5, 6, 7, 8, and 9 (P < or = 0.01 to 0.001) with a maximum ALG of 1.2 mm at 6 months. For BOP reduction, DH was superior to VC at all time points (P < or = 0.05) and to SC at months 3, 5, 6, 8, and 9 (P < or = 0.03). For DH, the maximum ALG in deep (> or = 7 mm) pockets was 1.7 mm and PDR 2.9 mm compared to 0.8 mm and 1.6 mm, respectively for moderate (5 to 6 mm) pockets. Test articles were applied without anesthesia and no serious adverse events occurred in the trial. The results of this study indicate that 10% doxycycline hyclate delivered in a biodegradable delivery system is an effective means of reducing the clinical signs of adult periodontitis and exhibits a benign safety profile.

2 multi-center trials assessing the clinical efficacy of 5% sanguinarine in a biodegradable drug delivery system.

A biodegradable drug delivery system containing 5% sanguinarium (Sa) was compared to vehicle control (VC), scaling and root planing (SRP), and supragingival plaque control (SPC) in the treatment of adult periodontitis in 2 well-controlled clinical trials. Studies were 4-quadrant (split mouth) designs at 2 centers each, having 94 (Study A) and 107 (Study B) patients. All patients had at least 3 pockets between 5 and 9 mm that bled on probing, in each quadrant. Probing pocket depth (PD), clinical attachment level (AL), bleeding on probing (BOP), and plaque index were recorded at baseline, 14, 30, 60, and 90 days. All treatments gave statistically significant reductions from baseline for PD and BOP, and significant gains for AL. For PD reduction, SRP was superior to all test groups at all time points in both studies (p < 0.001). Sa was superior to VC in Study A at 14 and 30 days and to SPC at all time points. For AL gain at 90 days, in both studies, SRP gave gains of 0.42 and 0.78 mm respectively with superiority seen over the SPC group at 90 days (p < 0.001) in study A only, For BOP reduction, in Study A SRP was superior to Sa, VC, and SPC at 60 and 90 days (p < 0.005) and in Study B superiority to Sa and VC was at 90 days and to SPC at 60 days (p < 0.05). Sa was superior to VC for pocket depth in deep pockets only. Sa failed to demonstrate superiority over VC on a consistent basis. Analysis of residual Sa indicates that Sa potency was insufficient to show an advantage beyond clinical effects inherent in treatments with VC and SPC.

Whole mouth microbiota effects following subgingival delivery of sanguinarium.

An increased incidence of antibiotic-resistant bacteria and yeast overgrowth has been reported following various periodontal treatments. The objective of this study was to detect possible overgrowth of opportunistic bacteria and fungi as well as changes in normal microbiota after application of a biodegradable delivery system containing 5% sanguinarium (ABDS-S) to one quadrant in a split-mouth study. An oral hygiene quadrant served as a control. The ABDS-S treated and control periodontal sites as well as the saliva of 17 subjects were sampled prior to treatment, immediately after ABDS-S removal at 7 days, and again at 30 and 60 days. At Day 7 sanguinarium-resistant bacteria increased in both control and ABDS-S periodontal sites as well as in the saliva. Enteric Gram-negative bacilli in both control and ABDS-S periodontal sites were 2.2 to 3.4 log colony forming units higher at Day 7 compared to baseline. This overgrowth was transient in that levels became undetectable at Days 30 and 60. No such overgrowth was observed for C. albicans or other fungi, or for S. aureus or other staphylococci in any periodontal sites. Levels of Actinomyces increased at Days 30 and 60 in both control and ABDS-S sites as well as saliva. These changes strongly suggest that a 7 day ABDS-S treatment in one quadrant of the mouth led to significant microbiota changes in the treated and control quadrants as well as in the saliva. Future microbial studies involving antimicrobials delivered by local delivery systems must consider the crossover effects of treatment inherent in the split-mouth design.

Guided tissue regeneration in human furcation defects after using a biodegradable barrier: a multi-center feasibility study.

This multi-center study evaluated guided tissue regeneration (GTR) in Class II furcation defects using a polylactic acid biodegradable barrier in 29 patients with mandibular and maxillary molar defects. Following an initial hygienic phase, surgical flaps were elevated, and the sites scaled and root planed. Furcation defect perimeter was measured and a customized barrier (thickness 600 to 750 mu) was applied to cover the defect. Barriers adhered directly to tooth and bone. At baseline, sites were measured for probing depth (PD) (6.0 +/- 0.2 [SE] mm), gingival margin location (GML) (-0.2 +/- 0.2 mm), and attachment level in both vertical (AL-V) (6.2 +/- 0.2 mm) and horizontal (AL-H) (5.4 +/- 0.2 mm) directions. After the surgical procedure, there was good compatibility between the gingival tissues and barrier material. Clinically, barriers fragmented and became displaced in 3 to 6 weeks. Substantial granulation tissue was sometimes present between barrier and root surfaces. Comprehensive periodontal examination parameters were measured 3, 4, 6, 9, and 12 months after baseline. A repeated measures ANOVA was used to evaluate changes from baseline. At 6 and 12 months postsurgery, GML was close to the presurgical level (-0.5 +/- 0.2 mm). There was clinically and statistically significant improvement in all other parameters: mean PD reduction (2.2 mm), AL-V gain (1.7 mm), and AL-H gain (2.5 mm). These results indicated favorable clinical regenerative outcomes after using this barrier material in Class II furcation defects in humans.

Reliability of crevicular fluid measurements taken in the presence of supragingival plaque.

The measurement of gingival crevicular fluid (GCF) is commonly used in clinical studies to quantitate the severity of gingival inflammation. This study examined the influence of the presence of supragingival plaque on GCF readings. Bilateral pairs of maxillary premolars received replicate GCF measurements. One of the teeth was randomly selected to be the test tooth. Supragingival plaque was removed from the test tooth between the first and second GCF measurements. Plaque was not removed from the control tooth. The crevicular fluid was collected on filter paper strips which were placed just subgingivally. The quantity of crevicular fluid was determined with the aid of the Periotron 6000. The mean difference between the first and second GCF measurement for the control teeth was -1.5 +/- 5.7 (+/- SD). This change was not significant (P = 0.21). The mean difference between the first and second GCF measurements for the experimental teeth (-21.3 +/- 16.5) was significant (P less than or equal to .001). The mean difference between the control and the experimental GCF differences were found to be highly significant (P less than or equal to .001). The data indicate that the presence of supragingival plaque can significantly elevate the GCF measurements when determined with the Periotron 6000.

An evaluation of the clinical analgesia/anesthesia efficacy on acute pain using the high frequency neural modulator in various dental settings.

The purpose of this study was to evaluate the effectiveness of high frequency neural modulation as a substitute for traditional local anesthesia in various dental procedures. This double-blinded study was done to evaluate patient comfort and degree of satisfaction as well as manageability of pain control by the operator during the dental procedures. Procedures included restorations, tooth extractions, root planing, pulp extirpation, and temporomandibular joint therapy. In the experimental group, favorable responses ranged from 0.0% to 92.8%, depending on the procedures. An overall favorable rating of 71.8% was given by the experimental group, and an overall favorable response of 8.5% was given by the placebo group.

Periodontal status in snow leopards.

Periodontal examinations were performed on ten 1- to 22-year-old snow leopards (6 males and 4 females), using dentistry methods for determining the plaque and gingival indices. All tooth surfaces were probed, and alveolar bone attachment loss was determined. After subgingival plaque removal, plaque specimens were examined for differential bacterial morphotypes. The small number of leopards evaluated precluded definitive statistical analysis. However, the progression from gingival health to gingivitis to periodontitis was similar to that seen in man. Therefore, the use of plaque index, gingival index, alveolar bone attachment loss, and differential bacterial morphotypes can be used to determine the dental health of snow leopards.