Furcation Therapy With Enamel Matrix Derivative

Study Overview
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Brief Summary
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Objective: To clinically evaluate mandibular furcation treated with Beta tricalcium phosphate/hydroxyapatite (βTCP/HA) isolated or combined with enamel matrix derivative (EMD + βTCP/HA) and EMD alone. Material and Methods: 39 patients, presenting at least one mandibular class II furcation defect, probing pocket depth (PPD) ≥ 4 mm and bleeding on probing, were included. The defects were assigned to the βTCP/HA group 1 (n = 13); open-flap debridement (OFD) + βTCP/HA filling; βTCP/HA + EMD group 2 (n = 13); OFD + βTCP/HA + EMD filling; and EMD group 3 (n = 13) OFD + EMD filling. Plaque (PI) and gingival index (GI), PPD, relative gingival margin position (RGMP), vertical and horizontal attachment level (RVCAL and RHCAL), and furcation diagnosis were evaluated at baseline, 6 and 12 months.

Detailed Description
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Although enamel matrix derivative (EMD) has been used to promote periodontal regeneration, little is known of its effect on the microbiome. Therefore, this investigation aimed to identify the changes in periodontal microbiome following treatment with EMD using a deep-sequencing approach. Thirty-nine patients having mandibular class II buccal furcation defects were randomized to beta-tricalcium-phosphate/hydroxyapatite graft (BONE group), EMD+BONE or EMD alone. Plaque was collected from furcation defects at baseline, 3 and 6 months post-treatment. Bacterial DNA was analyzed using terminal restriction fragment length polymorphism (t-RFLP) and 16S pyrotag sequencing. 169,000 classifiable sequences were compared to HOMD using the QIIME and PhyloToAST pipelines. Statistical comparisons were made using parametric tests. At baseline, a total of 422 species were identified from the 39 defects, belonging to Fusobacterium, Pseudomonas, Streptococcus, Filifactor and Parvimonas. All three regenerative procedures predictably altered the disease-associated microbiome, with a restitution of health-compatible species. However, EMD and BONE+EMD groups demonstrated more long-term reductions in higher number of species than in BONE group (p<0.05), especially disease-associated species e.g. Selenomonas noxia, F.alocis, and Fusobacterium. EMD may promote periodontal regeneration by predictably altering a dysbiotic subgingival microbiome, decreasing pathogen richness and increasing commensal abundance.

Official Title
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Furcation Therapy With Enamel Matrix Derivative: Effects on the Subgingival Microbiome

Conditions
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Chronic Periodontitis

Intervention / Treatment
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* Biological: Bone
* Biological: EMD


Participation Criteria
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Eligibility Criteria
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Inclusion Criteria: Untreated ChronicPeriodontitis Exclusion Criteria: Diabetes Pregnancy Current Smoking

Ages Eligible for Study
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Minimum Age: 21 Years
Maximum Age: 75 Years

Sexes Eligible for Study
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All

Accepts Healthy Volunteers
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Accepts Healthy Volunteers

Study Plan
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How is the study designed?
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Design Details

Primary Purpose: Treatment
Allocation: Randomized
Intervention Model: Parallel Assignment
Masking: Single


Arms and Interventions

| Participant Group/Arm | Intervention/Treatment |
| --- | --- |
| Placebo Comparator: BONE Group<br>bone substitute consisting of beta tricalcium phosphate/hydroxyapatite (βTCP/HA- Bone Ceramic® Straumann, Basel, Switzerland) | Biological: Bone<br>* Furcation defect regenerated with bone graft material<br>|
| Active Comparator: BONE+EMD Group<br>mixture of enamel matrix derivative proteins (EMD) (Emdogain® Straumann, Basel, Switzerland) and bone substitute consisting of βTCP/HA (Bone Ceramic® Straumann, Basel, Switzerland); | Biological: Bone<br>* Furcation defect regenerated with bone graft material<br>Biological: EMD<br>* Furcation defect regenerated with EMD<br>|
| Experimental: EMD Group<br>enamel matrix derivative (EMD - Emdogain® Straumann, Basel, Switzerland) | Biological: EMD<br>* Furcation defect regenerated with EMD<br>|

What is the study measuring?
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Primary Outcome Measures

| Outcome Measure | Measure Description | Time Frame |
| --- | --- | --- |
| Shifts in the subgingival microbiome at 3 and 6 months in response to the interventions | Subgingival microbial plaque samples will be collected at baseline and at the 3 and 6-month re-evaluation visits. Bacterial samples will be removed from the paper points by adding 200µl of phosphate buffered saline (PBS) and vortexing for 1 minute. The paper points were then removed, and DNA isolated using a Qiagen MiniAmp kit (Valencia, CA) according to the manufacturer's instructions. Multiplexed bacterial tag-encoded FLX amplicon pyrosequencing will be performed using the Titanium platform. High quality, classifiable sequences (quality score >25, >200bp length) were clustered into species-level operational taxonomic units (s-OTUs) at 97% sequence similarity and assigned a taxonomic identity by alignment to the HOMD database using the Blastn algorithm. Primary outcome measures will be changes in diversity, equitability and levels of pathogens. | 6 months |