The Effectiveness of Hyaluronic Acid in Bone Regeneration
- Conditions
- Socket Preservation
- Registration Number
- NCT07031895
- Lead Sponsor
- TC Erciyes University
- Brief Summary
Bone loss due to resorption is commonly observed in the alveolar socket following tooth extraction. This situation makes it difficult to preserve sufficient bone volume that would allow for ideal implant placement in cases requiring dental implants. Alveolar ridge preservation is a procedure aimed at minimizing bone resorption and preserving the volume and morphology of the alveolar ridge after tooth extraction.
The aim of this study is to evaluate the clinical effectiveness of socket preservation using a xenograft enriched with hyaluronic acid in patients with defective extraction sockets.
This study is designed as a randomized, controlled clinical trial including three parallel groups:
Study group - Patients whose alveolar bone was evaluated using cone-beam computed tomography (CBCT) will undergo tooth extraction, followed by the application of a bovine-derived graft/xenograft enriched with hyaluronic acid into the socket. Patients will be evaluated clinically, radiologically, and histologically at the 4th month. Dental implants will be placed in the edentulous areas where the graft was applied. Bone samples will be taken during the preparation of the implant sockets, and the bone tissue will be examined histologically. A third CBCT scan will be taken 6 months after implant placement to assess new bone formation and implant success radiographically.
Comparison group - Patients whose alveolar bone was evaluated using CBCT will undergo tooth extraction, followed by the application of a standard bovine-derived graft/xenograft into the socket. Patients will be evaluated clinically, radiologically, and histologically at the 4th month. Dental implants will be placed in the edentulous areas where the graft was applied. Bone samples will be taken during the preparation of the implant sockets, and the bone tissue will be examined histologically. A third CBCT scan will be taken 6 months after implant placement to assess new bone formation and implant success radiographically.
Control group - Patients whose alveolar bone was evaluated using CBCT will undergo tooth extraction, and the socket will be left to heal naturally without the application of any graft material. Patients will be evaluated clinically, radiologically, and histologically at the 4th month. Dental implants will be placed in the edentulous areas. Bone samples will be taken during the preparation of the implant sockets, and the bone tissue will be examined histologically. A third CBCT scan will be taken 6 months after implant placement to assess new bone formation and implant success radiographically.
- Detailed Description
Following tooth extraction, volume loss due to bone resorption is observed in the alveolar socket. This condition complicates the preservation of sufficient bone volume that would allow for ideal implant placement in cases requiring dental implants. Alveolar ridge preservation is a procedure aimed at minimizing bone resorption and maintaining the volume and morphology of the alveolar ridge after tooth extraction. In this procedure, the goal is to provide structural support and a scaffold for new bone formation by using materials such as autogenous grafts, allografts, xenografts, barrier membranes, platelet-rich fibrin, bone morphogenetic proteins, and other growth factors. This approach supports bone regeneration by promoting osteogenesis and osteoconduction. Although current methods maintain their effectiveness, variability in outcomes is still observed. This highlights the need for more extensive research into different graft materials and innovative approaches.
Hyaluronic acid has emerged as a promising biomaterial for alveolar ridge preservation due to its multifaceted biological effects on tissue regeneration and wound healing. Its viscoelastic properties help maintain hydration and structural integrity at the graft site, reducing graft shrinkage and supporting vertical stability. Additionally, by interacting with cell surface receptors, it stimulates osteoblast activity and inhibits osteoclastogenesis, thereby contributing to increased bone density and improved biointegration of the graft material. Clinical studies have also demonstrated that hyaluronic acid enhances angiogenesis, strengthening the osteoconductive properties of graft materials and optimizing clinical outcomes in alveolar ridge preservation.
The aim of this study is to evaluate the clinical efficacy of socket preservation using a xenograft enriched with hyaluronic acid in patients with defective extraction sockets. Over a 10-month period, the study group receiving a hyaluronic acid-enriched xenograft will be compared with a control group receiving a standard xenograft and another control group left to natural healing after tooth extraction. Evaluated outcomes include horizontal and vertical bone gain, graft stability, residual graft, bone marrow presence, and bone mineral density.
This study is designed as a randomized, controlled clinical trial including three parallel groups:
Study group - Patients whose alveolar bone is pre-evaluated using cone-beam computed tomography (CBCT) will receive a bovine-derived graft/xenograft enriched with hyaluronic acid in the extraction socket after tooth removal. Patients will be evaluated clinically, radiologically, and histologically at 4 months. Dental implants will be placed in the edentulous areas where the graft was applied. Bone samples will be collected during the preparation of the implant sockets and analyzed histologically. A third CBCT scan will be performed 6 months after implant placement to radiographically assess new bone formation and implant success.
Comparison group - Patients whose alveolar bone is pre-evaluated using CBCT will receive a standard bovine-derived graft/xenograft in the extraction socket after tooth removal. Patients will be evaluated clinically, radiologically, and histologically at 4 months. Dental implants will be placed in the grafted areas. Bone samples will be collected during implant socket preparation and analyzed histologically. A third CBCT scan will be performed 6 months after implant placement to assess new bone formation and implant success.
Control group - Patients whose alveolar bone is pre-evaluated using CBCT will undergo tooth extraction without graft material application, allowing for natural healing of the socket. Patients will be evaluated clinically, radiologically, and histologically at 4 months. Dental implants will be placed in the edentulous areas. Bone samples will be collected during the preparation of the implant sockets and analyzed histologically. A third CBCT scan will be performed 6 months after implant placement to assess new bone formation and implant success.
Histopathological Studies Tissue samples collected for histological analysis will be fixed in 10% formaldehyde solution for 72 hours. After fixation, samples will undergo decalcification using a solution composed of 10% formaldehyde, 80% distilled water, and 10% nitric acid. Following decalcification, standard histological tissue processing will be performed. Prepared sections will be stained with Hematoxylin and Eosin (H\&E) for general histological structure and Masson's Trichrome (MT) specifically for connective tissue evaluation. Microscopic evaluation will be performed using an Olympus BX51 light microscope (Olympus Corp., Tokyo, Japan) according to defined criteria, and measurements will be analyzed statistically using the ImageJ software program.
The obtained histological images will be evaluated according to Jerry Bouquot's classification (UTHSC School of Dentistry, Houston):
Grade 0 - No bone formation observed
Grade 1 - Minimal bone formation observed
Grade 2 - Moderate bone formation observed
Grade 3 - Considerable bone formation observed
Grade 4 - Extensive bone formation observed
Tissues collected from the study will also be analyzed using immunohistochemical staining to show the expression of Tartrate Resistant Acid Phosphatase (TRAP) and Alkaline Phosphatase (AP). For the different experimental groups, AP (Anti-Alkaline Phosphatase Antibody 100 μl, Abcam cat no: ab95462) will be used to demonstrate osteoblast activity, and TRAP (Rabbit Anti TRAP/Tartrate Resistant Acid Phosphatase Polyclonal Antibody, Bioss cat no: bs-6434R) will be used to determine osteoclast activity.
ImageJ software will be used at X40 magnification to calculate the intensity of AP and TRAP immunoreactivity in all femoral sections collected from the subjects in all experimental groups, and the results will be recorded.
Recruitment & Eligibility
- Status
- NOT_YET_RECRUITING
- Sex
- All
- Target Recruitment
- 60
- Socket type: Sockets with less than 50% bone resorption in the buccal and palatal/lingual walls according to the Kim JJ classification (Type I-IVa)
Age range: 18-65 years
Absence of active periodontal disease
No systemic diseases
Patients who will attend regular follow-up visits
- Smoking
Uncontrolled systemic disease
Presence of infection in the area
Use of medications affecting bone metabolism
Pregnancy or lactation
Study & Design
- Study Type
- INTERVENTIONAL
- Study Design
- PARALLEL
- Primary Outcome Measures
Name Time Method bone formation until the end of the histological examination 4 months after the socket preservation procedure At the 4-month follow-up, dental implants will be placed in the edentulous areas where grafts were applied. During the preparation of the implant sockets, bone samples will be collected and examined histologically.
Tissue samples obtained for histological examination will be fixed in a 10% formaldehyde solution for 72 hours. Following fixation, the tissues will undergo a decalcification process. After decalcification, a routine histological tissue processing protocol will be applied.
The obtained histological images will be evaluated according to the classification by Jerry Bouquot.
Tissues obtained from the study will also be analyzed using immunohistochemical staining under a light microscope (Olympus BX51, Tokyo, Japan). The sections will be examined under a light microscope (Olympus BX51, Tokyo, Japan). For all femoral sections obtained from subjects in the experimental groups, the intensity of AP and TRAP immunoreactivity will be calculated at 40× magnification using the ImageJ.
- Secondary Outcome Measures
Name Time Method Radiographic bone evaluation up to the radiographic evaluations at 4 and 10 months after the socket preservation procedure Cone-beam computed tomography (CBCT) scans will be obtained from each patient at three different time points throughout the study:
Before socket preservation
At 4 months after socket preservation (prior to implantation)
At 6 months after implantation
Using these scans, bone density, vertical and horizontal gain parameters will be measured.