Autogenous vs. Xenogeneic Peri-implant Soft Tissue Grafts Placed in Full vs. Split Thickness Flaps

Thin Gingiva Clinical Trial

Official title:

Randomised Clinical Trial Comparing Autogenous vs. Xenogeneic Peri-implant Soft Tissue Grafts Placed in Full vs. Split Thickness Flaps: a Clinical, Histological and Vascular Analysis

Clinical Trial Details — Status: Recruiting

Administrative data

• NCT number: NCT05211115
• Other study ID #: 19-102
• Status: Recruiting
• Phase: N/A
• Start date: January 24, 2022
• Est. completion date: December 1, 2024

Study information

• Verified date: May 2023
• Source: Universidad Complutense de Madrid
• Contact: Mariano Sanz Alonso
• Phone: +34 91 394 2021
• Email: marsan[@]ucm.es
• Is FDA regulated: No
• Study type: Interventional

Clinical Trial Summary

Randomized, outcome assessor and data analyst blinded, single center trial with four parallel arms and a 1:1:1:1 allocation ratio, with the aim of comparing which combination of bilaminar technique (split vs. full thickness flap) and graft type (autogenous or xenogeneic) provides better clinical, aesthetic, morphological, vascular and patients related outcomes, when augmenting the buccal peri-implant mucosa at the reopening of submerged implant fixtures

Description:

This randomized four parallel arms controlled clinical trial with blinded outcome assessment and data analysis aims to establish which combination of bilaminar technique (split vs. full thickness flap) and graft type (autogenous subepithelial connective tissue graft vs. volume stable collagen matrix) provides better clinical, aesthetic, morphological, vascular and patients related outcomes, when augmenting the buccal peri-implant mucosa at the reopening of submerged implant fixtures. The primary outcome is the gain in soft tissue thickness (standardised measurement at baseline, after surgery, at 1m and 6m). Secondary outcomes include changes in tissue volume (intraoral scans at baseline, post-op, 14d, 1m, 6m), RAL and KTW (clinical measurements at baseline, 1m, 6m), tissue color integration (∆E at 1m and 6m), and PROMS (7d, 14d, 30d). Exploratory outcomes include tissue morphology (histology at 1m,2m,4m,6m), microcirculation (Doppler flowmetry at pre-op, 7d, 14d, 1m) and revascularization (IHC at 1m,2m,4m,6m). A figure of 10 subjects per group was obtained for a 0,3mm difference in tissue thickness increase (SD 0,23mm), using 80% power, alpha 0.05, and a 10% drop-out rate. Patients will be randomly allocated to four groups: test (STF+VCM), control 1 (FTF+VCM), control 2 (SFT+CTG), control 3 (FTF+CTG). Patients will be the unit of analysis and ANOVA (normality) or Kruskall-Wallis (no normality) tests will be performed setting the significance level at p < 0.05.

Recruitment information / eligibility

• Status: Recruiting
• Enrollment: 40
• Est. completion date: December 1, 2024
• Est. primary completion date: December 15, 2023
• Accepts healthy volunteers: No
• Gender: All
• Age group: 18 Years and older

Eligibility

Inclusion Criteria:

Any male or female adult (= 18 year old) patient from the University Complutense of Madrid, being able to sign an informed consent form, presenting a submerged dental implant scheduled to undergo a second stage surgery, which is bounded mesially or distally by a remaining natural tooth, and exhibits a lack of buccal soft tissue volume, will be potentially eligible for this trial. The case definition for a lack of buccal soft tissue volume will be the presence of a thin buccal mucosa (< 2mm) or a minor volumetric contraction of the alveolar process (flat or concave buccal mucosal profile at the edentulous area). Exclusion Criteria: Patients fitting to all the above inclusion criteria will be not included in the study if unable to attend to the study-related procedures (including the follow-up visits) or if one or more of the following systemic or local exclusion criteria will be found during enrolment or through the study:

Systemic primary exclusion criteria:

• Compromised general health status contraindicating the study procedures (=ASA IV);
• Drug abuse, alcohol abuse, or smoking > 10 cigarettes a day;
• Chronic use of corticosteroids, NSAIDs, or immune-modulators (any type, any dose);
• Assumption of bisphosphonates (any type, any dose, past or present);
• Pregnant or nursing women;
• Hypersensitivity to paracetamol; Local primary exclusion criteria
• History of previous mucogingival surgeries in the area of interest;
• Lack of adequate vestibule depth to perform a bilaminar procedure;
• Lack of osseointegration at the time of implant reopening;
• Need for additional bone grafting at the time of implant reopening;
• Intraoperative evidence of a flap thickness < 0,5mm or > 2mm.

Secondary exclusion criteria:

• Non compliant patients: poor oral hygiene at 2 consecutive visits.

Related Conditions & MeSH terms

• Thin Gingiva

Intervention

Procedure:
• Split thickness flap
Palatally displaced crestal incision at the edentulous site, combined with the split thickness elevation of a buccal flap, extended to the sulcus of the adjacent mesial and distal tooth. Flap elevation performed with a micro-blade, in a buccal and apical direction, for approximately 15mm apical to the crestal incision.
• Full thickness flap
Palatally displaced crestal incision at the edentulous site, combined with the full thickness elevation of a buccal flap, extended to the sulcus of the adjacent mesial and distal tooth. Flap elevation performed with a fine periosteal elevator, in a buccal and apical direction, for approximately 15mm apical to the crestal incision.
• Autogenous sub epithelial connective tissue graft
Harvest of a sub epithelial connective tissue graft using a double incision technique, approximately 2-3 mm apical to the palatal gingival margins of the first and second premolars. Graft dimension standardised as 10mm (mesio-distally) by 6-8mm (apico-coronally) by 1,5mm (thickness). Graft stabilised at the inner aspect of the buccal flap, 1mm apical to the flap margin, using one mesial and one distal horizontal mattress sutures.
• Volume stable collagen matrix
Geistlich Fibro-Gide® matrix shaped at a standardised dimension of 10mm (mesio-distally) by 6-8mm (apico-coronally) by 6mm (thickness). Matrix stabilised at the inner aspect of the buccal flap, 1mm apical to the flap margin, using one mesial and one distal horizontal mattress sutures.

Locations

Country	Name	City	State
Spain	Department of Periodontology, University Complutense Madrid, Spain	Madrid

Sponsors (2)

Lead Sponsor	Collaborator
Universidad Complutense de Madrid	Osteology Foundation

Country where clinical trial is conducted

Spain, 

References & Publications (10)

Chappuis V, Araujo MG, Buser D. Clinical relevance of dimensional bone and soft tissue alterations post-extraction in esthetic sites. Periodontol 2000. 2017 Feb;73(1):73-83. doi: 10.1111/prd.12167. — View Citation

Johnston WM, Kao EC. Assessment of appearance match by visual observation and clinical colorimetry. J Dent Res. 1989 May;68(5):819-22. doi: 10.1177/00220345890680051301. — View Citation

McLean TN, Smith BA, Morrison EC, Nasjleti CE, Caffesse RG. Vascular changes following mucoperiosteal flap surgery: a fluorescein angiography study in dogs. J Periodontol. 1995 Mar;66(3):205-10. doi: 10.1902/jop.1995.66.3.205. — View Citation

Melzack R. The short-form McGill Pain Questionnaire. Pain. 1987 Aug;30(2):191-197. doi: 10.1016/0304-3959(87)91074-8. — View Citation

Perotto S, Romano F, Cricenti L, Gotti S, Aimetti M. Vascularization and Innervation of Connective Tissue Grafts in the Treatment of Gingival Recessions: A Histologic and Immunohistochemical Study. Int J Periodontics Restorative Dent. 2017 Jul/Aug;37(4):5 — View Citation

Rojo E, Stroppa G, Sanz-Martin I, Gonzalez-Martin O, Alemany AS, Nart J. Soft tissue volume gain around dental implants using autogenous subepithelial connective tissue grafts harvested from the lateral palate or tuberosity area. A randomized controlled c — View Citation

Sanz-Martin I, Encalada C, Sanz-Sanchez I, Aracil J, Sanz M. Soft tissue augmentation at immediate implants using a novel xenogeneic collagen matrix in conjunction with immediate provisional restorations: A prospective case series. Clin Implant Dent Relat — View Citation

Tatarakis N, Gkranias N, Darbar U, Donos N. Blood flow changes using a 3D xenogeneic collagen matrix or a subepithelial connective tissue graft for root coverage procedures: a pilot study. Clin Oral Investig. 2018 May;22(4):1697-1705. doi: 10.1007/s00784- — View Citation

Thoma DS, Naenni N, Figuero E, Hammerle CHF, Schwarz F, Jung RE, Sanz-Sanchez I. Effects of soft tissue augmentation procedures on peri-implant health or disease: A systematic review and meta-analysis. Clin Oral Implants Res. 2018 Mar;29 Suppl 15:32-49. d — View Citation

Thoma DS, Zeltner M, Hilbe M, Hammerle CH, Husler J, Jung RE. Randomized controlled clinical study evaluating effectiveness and safety of a volume-stable collagen matrix compared to autogenous connective tissue grafts for soft tissue augmentation at impla — View Citation

Outcome

Type	Measure	Description	Time frame	Safety issue
Primary	Buccal soft tissue thickness	Changes in the thickness of the buccal peri-implant mucosa, measured with trans-gingival probing.	before surgery, after surgery, 1 month after surgery, 6 months after surgery
Secondary	Volume changes	Changes in the size of the buccal peri-implant tissues and in their volume distribution, measured with a digital volumetric analysis.	before surgery, after surgery, 14 days after surgery, 1 month after surgery, 6 months after surgery
Secondary	Attachment level	Relative attachment level (implant) and clinical attachment level (adjacent tooth) measured with a standardised UNC-15 probe.	baseline, after surgery, 1 month after surgery, 6 months after surgery
Secondary	Colorimetric integration	Colorimetric integration of the augmented buccal peri-implant mucosa, relative to the buccal attached gingiva of the mesial and distal adjacent tooth, quantified throughout the ?E score, calculated on standardised digital photographs.	1 month after surgery, 6 months after surgery
Secondary	Patients related outcome measures	Patients pain and discomfort with respect to the procedure evaluated with the short form of the McGill pain questionnaire (SF-MPQ).	7 days after surgery, 14 days after surgery, 1 month after surgery, 6 months after surgery
Secondary	Microcirculation of the grafted area	Microcirculation of the treated area evaluated with a laser Doppler flowmeter.	before surgery, after surgery, 7 days after surgery, 14 days after surgery, 1 month after surgery, 6 months after surgery
Secondary	Morphology of the grafted area	Descriptive histology performed on paraffin embedded sections from buccal gingival specimens, stained with hematoxylin-eosin.	1 month after surgery or 2 months after surgery or 4 months after surgery or 6 months after surgery
Secondary	Revascularization and reinnervation of the grafted area	Immune histochemistry performed on paraffin embedded, hematoxylin-eosin stained sections using markers of tissue revascularization and reinnervation.	1 month after surgery or 2 months after surgery or 4 months after surgery or 6 months after surgery
Secondary	Full mouth Plaque score	Full muouth plaque score measured with a standardised UNC-15 probe.	baseline, after surgery, 1 month after surgery, 6 months after surgery
Secondary	Full mouth Bleeding score	Full mouth bleeding score measured with a standardised UNC-15 probe.	baseline, after surgery, 1 month after surgery, 6 months after surgery
Secondary	Keratinised tissue width	Keratinised tissue width measured with a standardised UNC-15 probe.	baseline, after surgery, 1 month after surgery, 6 months after surgery
Secondary	Bleeding on probing	Presence/absence of bleeding on probing at the treated implant measured with a standardised UNC-15 probe.	baseline, after surgery, 1 month after surgery, 6 months after surgery
Secondary	Modified Plaque index	Presence/absence of plaque at the treated implant	baseline, after surgery, 1 month after surgery, 6 months after surgery