Dental Implantation, Peri-Implant Soft Tissue Deficiency, Soft Tissue Augmentation
Conditions
Brief summary
Peri-implant soft-tissue defects will be treated with either a volume-stable collagen matrix (VCMX; test group) or an autogenous connective tissue graft (CTG; control group) following implant placement in patients with a single missing tooth. After a mid-crestal incision and full-thickness flap elevation, the graft material will be positioned over the crest beneath the buccal flap and stabilized, followed by tension-free primary closure. Peri-implant soft-tissue thickness, echo intensity, and vascularization will be assessed non-invasively using high-resolution intraoral ultrasonography and Power Doppler imaging. Clinical periodontal parameters and patient-reported outcomes, including pain perception (visual analog scale), swelling, fatigue, analgesic consumption, and wound healing, will be recorded. These outcomes will be evaluated at baseline and on the 1st week, 1st, 3rd, and 6th months. At the 6th month, gingival biopsy samples obtained during healing abutment placement will be evaluated histologically and immunohistochemically (CD11c, CD163, COL1, COL3, MMP-1, TIMP-1) to compare the biological integration of the two graft materials.
Detailed description
Adequate peri-implant soft-tissue thickness is important for both esthetic outcomes and the long-term maintenance of peri-implant health, as thin mucosa has been associated with increased marginal bone loss. Although the autogenous connective tissue graft is considered the gold standard for soft-tissue augmentation, it entails disadvantages such as the need for a second surgical site and donor-site morbidity. The volume-stable collagen matrix has been proposed as an alternative that eliminates the need for a donor site; however, comparative data based on ultrasonographic, histological, and immunohistochemical evidence remain limited. This study aims to compare VCMX and CTG using a multidimensional approach. The study is designed as a single-center, randomized, controlled clinical trial to be conducted at the Department of Periodontology, Faculty of Dentistry, Ankara University. Participants meeting the eligibility criteria will be allocated to the test (VCMX) and control (CTG) groups. All surgical and clinical procedures will be performed according to standardized protocols, and all data will be recorded prospectively. The evaluation will adopt a multidimensional methodological approach: the assessment of quantitative data obtained by high-resolution intraoral ultrasonography (soft-tissue thickness, vascularization, and echo intensity) together with histological and immunohistochemical findings constitutes the novel aspect of this study. The primary outcome will be the change in ultrasonographic soft-tissue thickness, whereas the secondary outcomes will comprise vascularization, echo intensity, clinical periodontal parameters, patient-reported outcomes, and the histological/immunohistochemical evaluation of graft integration. In this way, the two graft materials will be compared not only in terms of dimensional gain but also with respect to biological integration and tissue quality.
Interventions
PROCEDUREConnective tissue graft
An autogenous connective tissue graft harvested from the palate using the extraoral de-epithelialization technique will be placed over the crest beneath the buccal flap and stabilized with simple interrupted sutures (6-0 polypropylene) to augment peri-implant soft-tissue thickness. (control group)
A volume-stable porcine-derived collagen matrix (15×20×3 mm) will be trimmed to the defect size, placed over the crest beneath the buccal flap, and stabilized with simple interrupted sutures (6-0 polypropylene) to augment peri-implant soft-tissue thickness. (test group)
Sponsors
Ankara University
Study design
Allocation
RANDOMIZED
Intervention model
PARALLEL
Primary purpose
TREATMENT
Masking
DOUBLE (Investigator, Outcomes Assessor)
Eligibility
Sex/Gender
ALL
Age
18 Years to 65 Years
Healthy volunteers
Yes
Inclusion criteria
* Age \>18 years * Periodontal health confirmed according to the 2017 World Workshop criteria (BOP \<10%, PD ≤3 mm, absence of gingival inflammation, and good oral hygiene) (Tonetti et al., 2018) * Requirement of implant placement and soft-tissue augmentation for a single missing tooth in the anterior region * Bleeding on probing \<30% at the adjacent teeth (Thoma et al., 2016) * Compliance with the study protocol and follow-up visits
Exclusion criteria
* Siebert Class II or Class III defects * History of surgery at the treated site * Untreated periodontitis or peri-implantitis * Current smoking or smoking within the previous five years * Systemic conditions (that may impair healing) * Pregnancy or lactation * Allergy to the materials/drugs used * Drug use affecting mucosal healing * History of antibiotic therapy within the previous six months
Design outcomes
Primary
| Measure | Time frame | Description |
|---|---|---|
| peri-implant soft-tissue thickness | Baseline, 1 week, 1 month, 3 months, and 6 months | Peri-implant buccal soft-tissue thickness will be measured non-invasively using high-resolution intraoral ultrasonography (LOGIQ P10 XDClear R4.5, GE Healthcare) with an L8-18i-RS high-frequency linear "hockey-stick" probe (8 MHz). Measurements will be repeated preoperatively (baseline) and postoperatively at 1 week, 1 month, 3 months, and 6 months. On static B-mode images, linear soft-tissue thickness will be assessed at three levels 1.5, 3, and 5 mm apical to the alveolar crest margin and recorded in millimeters by a single calibrated examiner blinded to group allocation. The primary outcome is the change in linear soft-tissue thickness from baseline to 6 months, compared between the VCMX and CTG groups. |
Secondary
| Measure | Time frame | Description |
|---|---|---|
| Peri-implant soft-tissue vascularization | Baseline, 1 week, 1 month, 3 months, and 6 months | Peri-implant soft-tissue perfusion will be evaluated using Power Doppler ultrasonography (PDUS) with the same unit and probe, preoperatively (baseline) and postoperatively at 1 week, 1 month, 3 months, and 6 months. Quantitative analysis will use the device's integrated Color Quantification (CQ) module: a circular region of interest (ROI) 6 mm in diameter (area 28.274 mm²), originating from the alveolar crest margin, will be defined. Within this ROI, the proportion of colored (Power Doppler) pixels representing blood flow relative to the total number of pixels will be calculated to obtain a semi-quantitative Power Doppler pixel density . The outcome is the change in pixel density from baseline to 6 months, compared between the VCMX and CTG groups. |
| Ultrasonographic echo intensity of peri-implant soft tissue | Baseline, 1 week, 1 month, 3 months, and 6 months | Tissue echogenicity will be evaluated preoperatively (baseline) and postoperatively at 1 week, 1 month, 3 months, and 6 months from static B-mode images obtained with the probe positioned longitudinally over the mid-buccal region of the edentulous site. Echo intensity will be measured in decibels (dB) using the unit's grayscale (echo-intensity) function. The ROI will extend 7 mm apically from the soft-tissue margin. As the device references echo intensity to the system's saturation level, soft-tissue reflections yield negative dB values; less negative values indicate higher echogenicity (denser, more organized tissue), and more negative values indicate hypoechoic/less dense tissue. Measurements will be performed by a single calibrated, blinded examiner, with intra-examiner reliability assessed beforehand. The outcome is the change in echo intensity from baseline to 6 months, compared between the VCMX and CTG groups. |
| Postoperative pain | 1 week | Patient-rated pain intensity at 1 week, recorded on a Visual Analog Scale (VAS) anchored at 0 (no pain) and 10 (most severe pain). Compared between the VCMX and CTG groups. |
| Postoperative swelling | 1 week | Patient-rated swelling at 1 week on a Visual Analog Scale (VAS) from 0 (no swelling) to 10 (most severe). Compared between the VCMX and CTG groups. |
| Postoperative fatigue | 1 week | Patient-rated fatigue at 1 week on a Visual Analog Scale (VAS) from 0 (no fatigue) to 10 (most severe). Compared between the VCMX and CTG groups |
| Number of analgesic tablets consumed | 1 week | Total number of analgesic tablets taken during the first postoperative week, recorded by patient self-report. Compared between the VCMX and CTG groups. |
| Early wound healing (Wound Healing Index, WHI) | 1 week | Early wound healing at 1 week scored with the Wound Healing Index (Huang et al., 2005) based on edema, erythema, discomfort, flap dehiscence, and suppuration, from 1 (uneventful healing) to 3 (poor healing). Compared between the VCMX and CTG groups. |
| Soft-tissue appearance | 6 months | Soft-tissue appearance at 6 months graded with the Aichelmann-Reidy et al. (2001) tissue-appearance system across five parameters (tissue consistency, contour, color match, scar formation, and integration with adjacent tissue), each scored against predefined criteria and summed into a total appearance score. Compared between the VCMX and CTG groups. |
| Patient satisfaction with appearance | 6 months | Number of participants rating the appearance of the treated site as "satisfactory" versus "not satisfactory" at 6 months. Compared between the VCMX and CTG groups. |
| Patient satisfaction with experience | 6 months | Number of participants rating their treatment experience as "satisfactory" versus "not satisfactory" at 6 months. Compared between the VCMX and CTG groups. |
| Histomorphological evaluation | 6 months | Descriptive light-microscopic evaluation (hematoxylin-eosin and Masson's trichrome) of tissue architecture, integrity and cellular organization, extracellular matrix organization, and the presence of necrosis, edema, hemorrhage, inflammation, foreign-body reaction, and fibrosis. |
| Microvascular density | 6 months | Number of vessels counted in the superficial connective tissue at x400 magnification (single field = 0.237 mm²) across three consecutive fields, averaged per specimen. Compared between the VCMX and CTG groups. |
| CD163 | 6 months | Number of CD163-positive cells counted at x400 magnification (single field = 0.237 mm²) across three hot-spot fields, averaged per specimen. Compared between the VCMX and CTG groups. |
| CD11c | 6 months | Number of CD11c-positive cells counted at x400 magnification (single field = 0.237 mm²) across three hot-spot fields, averaged per specimen. Compared between the VCMX and CTG groups. |
| TIMP-1 | 6 months | Number of TIMP-1 positive cells counted at x400 magnification (single field = 0.237 mm²) across three hot-spot fields, averaged per specimen. Compared between the VCMX and CTG groups. |
| MMP-1 | 6 months | Number of MMP-1 positive cells counted at x400 magnification (single field = 0.237 mm²) across three hot-spot fields, averaged per specimen. Compared between the VCMX and CTG groups. |
| Collagen I | 6 months | Immunohistochemical Collagen I staining, quantified as the percentage of positively stained area relative to the total microscopic field area. Compared between the VCMX and CTG groups. |
| Collagen III | 6 months | Immunohistochemical Collagen III staining, quantified as the percentage of positively stained area relative to the total microscopic field area. Compared between the VCMX and CTG groups. |
Countries
Turkey (Türkiye)
Contacts
CONTACTSivge Kurgan, PHD
CONTACTMerve Atak, DDS
Outcome results
None listed