Biofunctionalization of a Volume-stable Collagen Matrix (VCMX) for the Treatment of Single Gingival Recession

Study Overview
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Brief Summary
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The treatment of single gingival recessions comprises different well-established techniques, and the association between coronally advanced flap (CAF) and the subepithelial connective tissue graft is considered the gold standard. However, despite the excellent clinical results obtained, the use of subepithelial connective tissue graft is related to an increased risk of trans and postoperative bleeding, a longer duration of the surgical procedure and greater postoperative pain and morbidity. To overcome these limitations and increase patient acceptance, new biomaterials have been developed as possible alternatives to the use of connective tissue graft. Recently, tissue engineering has been investigating collagen matrices as carriers of biologically active substances. In vitro and in vivo studies have shown that the biofunctionalization of these matrices using injectable platelet rich-fibrin (i-PRF) can optimize the healing process of soft tissues using own's patient regenerative components. However, although it has promising potential, clinical studies evaluating the performance of functionalized collagen matrices are still scarce in the literature. Thus, the present study aims to evaluate the clinical, esthetic, patient-centered, immuno and microbiological results of the use of the biofunctionalized volume stable collagen matrix (VCMX) for the treatment of single gingival recessions RT1. For such purpose, a randomized controlled clinical trial of superiority, parallel and blind will be carried out. Seventy-five patients with RT1 single gingival recession will be selected, who will be randomly allocated to one of the following groups: CAF+VCMX+i-PRF (n = 25), coronally advanced flap associated with VCMX functionalized with i-PRF; CAF+VCMX (n=25), coronally advanced flap associated with VCMX; and CAF group (n = 25), coronally advanced flap alone (CAF). The groups will be compared regarding clinical, esthetic and patient-centered outcomes at the baseline, three and six months after the surgical procedure. The microbiological evaluation will be performed at baseline, three and six months after surgery and the concentration of inflammatory markers and growth factors will be assessed before the procedure and 3, 7, 14, 30 and 60 days after treatment.

Official Title
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Functionalization of a Volume-stable Collagen Matrix (VCMX) Using Injectable Platelet Rich Fibrin (i-PRF) for the Treatment of Single Gingival Recession

Conditions
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Gingival Recession

Intervention / Treatment
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* Procedure: CAF
* Procedure: i-PRF
* Device: VCMX
* Drug: Sodium dipyrone
* Drug: Chlorhexidine rinse
* Drug: Amoxicillin 500mg


Participation Criteria
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Eligibility Criteria
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Inclusion Criteria: Presence of RT1 (Cairo et al., 2011) buccal single gingival recession (GR) on vital upper or lower canines and premolars with intact root surface (visible CEJ). Presence of dentin hypersensitivity (HD) and/or esthetic concerns related to GR. Adults > 18 years old. Systemically health. No signs of active periodontal disease. Full-mouth plaque and bleeding score ≤ 20%. Written informed consent given. Exclusion Criteria: Smoking. Contraindication for periodontal surgery. Pregnancy. Presence of orthodontic braces. Medications known to interfere with periodontal healing. Use of anticoagulants.

Ages Eligible for Study
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Minimum Age: 18 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: Parallel assignment
Masking: Double


Arms and Interventions

| Participant Group/Arm | Intervention/Treatment |
| --- | --- |
| Experimental: CAF+VCMX+i-PRF<br>The surgical procedure for root coverage will be the trapezoidal-type of coronally advanced flap previously described (de Sanctis & Zucchelli 2007). Thus, it will start with two divergent releasing incisions lateral to the gingival recession defect. These releasing incisions will then be united by a sulcular incision, and the flap will be raised beyond the mucogingival junction. Subsequently, a VCMX functionalized with injectable platelet rich-fibrin (I-PRF) will be placed at the cemento-enamel junction (CEJ) level and stabilized in the adjacent interdental connective beds by interrupted sutures. Then, sling sutures will be placed to stabilize the flap margin 2 mm coronal to CEJ, followed by interrupted sutures to close the releasing incisions. | Procedure: CAF<br>* Periodontal surgical technique to treat gingival recessions<br>* Other names: Periodontal plastic surgery;Procedure: i-PRF<br>* Blood-derived biomaterial. Two sterile plastic tubes (Process for PRF, Nice, France) with a volume of 10 ml will be used to generate fluid blood concentrate. After blood collection, the tubes will be centrifuged using a Duo centrifuge (Process for PRF, Nice, France) (fixed angle rotor with a radius of 110 mm) following the protocol proposed by Choukroun et al. (2018) (600 rpm; 8 min).<br>* Other names: injectable platelet rich-fibrin;Device: VCMX<br>* Porcine derived collagen matrix.<br>* Other names: Geistlich Fibro-Gide;Drug: Sodium dipyrone<br>* All participants will be instructed to take 500 mg sodium dipyrone just in case of pain.<br>* Other names: Drug prescription;Drug: Chlorhexidine rinse<br>* All participants will be instructed to perform 0.12% chlorhexidine rinse after the surgical procedures.<br>* Other names: Drug prescription;Drug: Amoxicillin 500mg<br>* Participants enrolled in the CAF+VCMX and CAF+VCMX will be instructed to take amoxicillin 500mg (8 hours/8 hours, during 7 days) after the surgical procedures.<br>* Other names: Drug prescription;|
| Experimental: CAF+VCMX<br>The surgical procedure for root coverage will be the trapezoidal-type of coronally advanced flap previously described (de Sanctis & Zucchelli 2007). Thus, it will start with two divergent releasing incisions lateral to the gingival recession defect. These releasing incisions will then be united by a sulcular incision, and the flap will be raised beyond the mucogingival junction. Subsequently, a VCMX will be placed at the cemento-enamel junction (CEJ) level and stabilized in the adjacent interdental connective beds by interrupted sutures. Then, sling sutures will be placed to stabilize the flap margin 2 mm coronal to CEJ, followed by interrupted sutures to close the releasing incisions. | Procedure: CAF<br>* Periodontal surgical technique to treat gingival recessions<br>* Other names: Periodontal plastic surgery;Device: VCMX<br>* Porcine derived collagen matrix.<br>* Other names: Geistlich Fibro-Gide;Drug: Sodium dipyrone<br>* All participants will be instructed to take 500 mg sodium dipyrone just in case of pain.<br>* Other names: Drug prescription;Drug: Chlorhexidine rinse<br>* All participants will be instructed to perform 0.12% chlorhexidine rinse after the surgical procedures.<br>* Other names: Drug prescription;Drug: Amoxicillin 500mg<br>* Participants enrolled in the CAF+VCMX and CAF+VCMX will be instructed to take amoxicillin 500mg (8 hours/8 hours, during 7 days) after the surgical procedures.<br>* Other names: Drug prescription;|
| Active Comparator: CAF<br>The surgical procedure for root coverage will be the trapezoidal-type of coronally advanced flap previously described (de Sanctis & Zucchelli 2007). Thus, it will start with two divergent releasing incisions lateral to the gingival recession defect. These releasing incisions will then be united by a sulcular incision, and the flap will be raised beyond the mucogingival junction. Then, sling sutures will be placed to stabilize the flap margin 2 mm coronal to CEJ, followed by interrupted sutures to close the releasing incisions. | Procedure: CAF<br>* Periodontal surgical technique to treat gingival recessions<br>* Other names: Periodontal plastic surgery;Drug: Sodium dipyrone<br>* All participants will be instructed to take 500 mg sodium dipyrone just in case of pain.<br>* Other names: Drug prescription;Drug: Chlorhexidine rinse<br>* All participants will be instructed to perform 0.12% chlorhexidine rinse after the surgical procedures.<br>* Other names: Drug prescription;Drug: Amoxicillin 500mg<br>* Participants enrolled in the CAF+VCMX and CAF+VCMX will be instructed to take amoxicillin 500mg (8 hours/8 hours, during 7 days) after the surgical procedures.<br>* Other names: Drug prescription;|

What is the study measuring?
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Primary Outcome Measures

| Outcome Measure | Measure Description | Time Frame |
| --- | --- | --- |
| Gingival recession reduction (RecRed) | Final depth of gingival recession in millimeters minus gingival margin initial position in millimeters measured through a periodontal probe. | 6 months | 

Secondary Outcome Measures

| Outcome Measure | Measure Description | Time Frame |
| --- | --- | --- |
| Root coverage esthetic score | The Root Coverage Esthetic Scale (RES; Cairo et al., 2009) will be performed by two blinded and independent examiners at the 6-month post-operative assessment. This score evaluates five variables: level of the gingival margin, marginal tissue contour, soft tissue texture, mucogingival junction alignment, and gingival color. | 6 months | 
| Dentine hypersensitivity | Evaluation of root sensitivity with the air blow test and measurement with a visual analog scale (VAS). | 6 months | 
| Patient recovery | Evaluation of postsurgery sequelae, pain, and discomfort, oral function and interference with daily activities through postoperative diary previously described (Tonetti et al. 2018). | 14 days | 
| Patient-centred esthetic evaluation | Esthetic evaluation performed by the patient through a visual analog scale (VAS). | 6 months | 
| Immunological evaluation | Gingival crevicular fluid will be collected in order to evaluate the levels of nine inflammatory markers: IL1β, IL4, IL5, IL6, IL9, IL10, IL17A, Interferon gamma-induced protein 10 kDa (IP10), macrophage inflammatory protein 1α (MIP1α), monocyte chemotactic protein 1α (MCP-1α), and tumor necrosis factor α (TNFα). The following growth factors will be evaluated: EGF, TGF, PDGF, FGF, and VEGF. In addition, MMP-1, MMP-2 from TIMP-1, and TIMP-2 will also be evaluated. | Baseline, 3, 7, 14, 30, and 60 days after surgery | 
| Microbiological evaluation | The collection of the subgingival biofilm will be performed in order to quantificate microorganisms such as Porphyromonas gingivalis, Tannerella forsythia, Prevotella intermedia, Fusobacterium nucleatum e Streptococcus sanguinis. | Baseline, 45 days, and 6 months after the procedure. | 

 Terms related to the study
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Keywords Provided by Centre Hospitalier Valida
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Platelet-rich fibrin, Gingival Recession