The Healing of Soft Tissue Augmentation by Acellular Dermal Matrix and Autogenous Subepithelial Connective Tissue Graft

Study Overview
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Brief Summary
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The study team proposes to prospectively compare the healing outcomes of autogenous soft tissue connective tissue graft (CTG) and Acellular dermis matrix (ADM) in a split-mouth design study for patients requiring modification of gingival soft tissue biotype. The researchers aim to investigate the earlier phase of graft healing after the grafting surgery by biopsy histology and by examining the alteration of gene profile during the healing of gingival tissue healing by molecular cell biological techniques.

Detailed Description
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The investigators will perform a prospective clinical randomized controlled trial, and recruit 12 patients who need gingival soft tissue augmentation. It is a split-mouth design: CTG will be used in one side of soft tissue augmentation, and ADM will be used on the other side. 3 months after graft healing, clinical measurements including soft tissue thickness, transparency visualization, tissue profile record with impression cast study model, and digital photography of tissue will be performed. The gingival punch biopsies ( 2mm diameters) will be performed in both sides of grafting areas under the local oral anesthesia injection. The collected tissue will be split into two halves, one for histological examination, and another half for gene analysis.

Official Title
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The Study on the Healing of Soft Tissue Augmentation by the Acellular Dermal Matrix and Autogenous Subepithelial Connective Tissue Graft

Conditions
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Gingival Recession, Generalized, Graft Reaction

Intervention / Treatment
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* Procedure: Gingival Punch Biopsy after healing of Gingival Soft Tissue Augmentation


Participation Criteria
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Eligibility Criteria
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Inclusion Criteria: general healthy periodontal healthy (no PD >3mm, no BOP, no mobility at the test site and control site) patients identified need gingival biotype modification (need for increased tissue thickness) during the periodontal exam or referred from orthodontics Exclusion Criteria: current smoker or smoking history taking Antibiotics or medicines within the last 3 months past history of gingival soft tissue augmentation/modification surgery

Ages Eligible for Study
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Minimum Age: 18 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
Interventional Model Description: Patients needing gingival soft tissue augmentation will receive two kinds of gingival tissue graft material in a split-mouth design. The autogenous connective tissue (CTG) graft material will be randomized to apply to one half, and commercial acellular dermal matrix (ADM) materials will be used in the opposite half.
Masking: Single


Arms and Interventions

| Participant Group/Arm | Intervention/Treatment |
| --- | --- |
| Active Comparator: CTG Group<br>Patients needing gingival soft tissue augmentation will receive two kinds of gingival tissue graft material in a split-mouth design. In this group, the autogenous connective tissue graft (CTG) material will be randomized to transplant to one side of the arch. | Procedure: Gingival Punch Biopsy after healing of Gingival Soft Tissue Augmentation<br>* Patients needing gingival soft tissue augmentation will receive two kinds of gingival tissue graft material in a split-mouth design. The autogenous connective tissue (CTG) graft material will be randomized to apply to one half, and commercial acellular dermal matrix (ADM) materials will be used in the opposite half. After 3 months of healing, a gingival punch biopsy will be performed in both sides to collect the tissues for analysis.<br>|
| Active Comparator: ADM Group<br>The patients needing gingival soft tissue augmentation will receive two kinds of gingival tissue graft material in a split-mouth design. In this group, the commercial acellular dermal matrix (ADM) materials will be transplanted to the opposite side of the arch with CTG transplants. | Procedure: Gingival Punch Biopsy after healing of Gingival Soft Tissue Augmentation<br>* Patients needing gingival soft tissue augmentation will receive two kinds of gingival tissue graft material in a split-mouth design. The autogenous connective tissue (CTG) graft material will be randomized to apply to one half, and commercial acellular dermal matrix (ADM) materials will be used in the opposite half. After 3 months of healing, a gingival punch biopsy will be performed in both sides to collect the tissues for analysis.<br>|

What is the study measuring?
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Primary Outcome Measures

| Outcome Measure | Measure Description | Time Frame |
| --- | --- | --- |
| The histological analysis of the gingival biopsy tissue. | Histological analysis with standard coloration will assess the epithelium and underneath connective tissue within the gingival biopsy tissue. Signs of inflammation (ulcerations, infiltration of neutrophil cells, vessel structure) will be noted. | Month 3---after the gingival biopsy procedures | 

Secondary Outcome Measures

| Outcome Measure | Measure Description | Time Frame |
| --- | --- | --- |
| The immunohistological analysis of the gingival biopsy. | Immunohistological analysis using specific antibodies will locate the epithelium (collagen IV), the smooth muscle (Smooth muscle actin), and re-innvervation (protein gene product 9.5, calcitonin-related gene product) according to the similar study by Perotto, et al. 2017. | Month 3---after the gingival biopsy procedures | 
| RT-qPCR analysis of gingival biopsy. | The RT-qPCR analysis will measure the level of expression (compared to the housekeeping gene GAPDH) of RNA specific to the epithelium (collagen IV), the smooth muscle (Smooth muscle actin), re-innvervation (protein gene product 9.5, calcitonin-related gene product) and inflammation (IL-1, IL-6, MMP-8, TNF-alpha). | Month 3---after the gingival biopsy procedures |