Hyaluronic Acid and Polynucleotides in Ridge Preservation

Official title

The Use of Hyaluronic Acid and Polynucleotides in Ridge Preservation Sites Rehabilitated With a Complete Full Digital Workflow

Overview

The aim of this study is to test the use of a bovine-derived bone graft combined with a polynucleotides-rich hyaluronic acid (PNHA) gel for the preservation of the bone after a tooth extraction (alveolar ridge preservation) and to test the performance of a fully-digital workflow to rehabilitate the site with a dental implant. 40 patients in need for a single tooth extraction will be recruited at Centro di Odontoiatria, Università di Parma and they will be randomly assigned to 2 groups: extraction and spontaneous healing or extraction and regeneration of the site with a bovine-derived bone graft combined with a PNHA gel. At 4 months after extraction an implant will be placed in the extraction site, which will be rehabilitated with a fully-digital workflow and patients will be followed up at up to 12 months post rehabilitation. Two 3D x-rays with a small field of view will be performed immediately after extraction and at 4 months post extraction to plan implant placement. These images will also be used to assess changes in the dimension of the post extraction bone (primary outcome). As part of the study different questionnaires will be administered to assess quality of life and perception of the therapy and the wound exudate in the area of the extraction will be collected non invasively with a collagen sponge to assess the expression of different proteins during the early healing days. On the day of implant placement a sample of bone tissue will also be collected as part of the bone drilling and histologically analysed.

Detailed description

This is a single-centre, double-blind RCT involving 40 patients in need for a single tooth extraction to be replaced with a dental implant. The study consists of 11 visits, over a minimum period of 20 months. Participants will be recruited at Centro di Odontoiatria, at Università di Parma amongst patients routinely seen in new patient clinics and follow-up clinics. After atraumatic tooth extraction, participants will be randomly allocated to one of the following treatment groups: - DBBM (Bio-oss, Geistlich) mixed with a PNHA gel (Regenfast, Mastelli) and socket sealed with a porcine collagen matrix (Mucograft seal, Geistlich) (Test); - Unassisted socket healing (Control). Patient post-operative discomfort will be assessed with a visual analogue scale (VAS) and through clinician-reported post-operative oedema/swelling. Clinical evaluation of socket healing and recording of soft tissue healing index of Landry will also be performed during the early post-extraction days. With the help of a sterilecollagen sponge, wound exudate will be collected at 3, 7 and 14 days post extraction. A CBCT with a small field of view (e.g. 5X8 cm) will be taken to assess the post-extraction socket dimensions and after 4 months to plan implant placement. The CBCT scan will be processed with its embedded segmentation function to remove scattering defects and obtain the maximal possible quality.

Changes in alveolar ridge width from the extraction until 4 months post extraction between the 2 groups will be assessed with a dedicated software (e.g. SMOP) (primary outcome).

On the day of implant placement, a bone core biopsy will be collected from the drilling site. Undecalcified histology analysis will be done, and qualitative histology will be performed by a blind examiner, who will assess the level of maturation of the tissue in the two groups. Moreover, histomorphometric measurements will be recorded and presented descriptively, including amount of mineralized bone, as well as other standard parameters, such as %graft particles (test group only) and % of immature woven bone. A fully digital workflow will be followed to rehabilitate the patients, which will be followed up at up to 12 months post implant loading.

Interventions

• Device regeneration of post extraction socket with biomaterials
  after tooth extraction, in the test group we will place a demineralised bovine bone graft mixed with a gel containing hyaluronic acid and polynucleotide and we will cover the entrance of the socket with a collagen matrix

Primary outcome measures

• Change in alveolar ridge width at 4 months post extraction between study groups [Time frame: 4 months after tooth extraction (visit 6)]

Secondary outcome measures (12)

• quality of newly formed bone [Time frame: 4 months post extraction (visit 6)]
• 3D volume changes [Time frame: 4 months post extraction (visit 6)]
• changes in protein expression [Time frame: 3, 7 and 14 days post extraction (Visit 3, 4, 5)]
• Profilometric changes [Time frame: 3, 7, 14 days and at 4 months post extraction (visit 3, 4, 5)]
• Change in post operative discomfort [Time frame: 3, 7 and 14 days after extraction (visit 3, 4, 5)]
• Change in Landry healing index [Time frame: 3, 7 and 14 days after extraction (Visit 3, 4, 5)]
• Changes in keratinized tissue [Time frame: 4 months post extraction (Visit 6) and at study termination 12 months post loading (Visit 10);]
• Qualitative assessment of post-operative need for medications [Time frame: Starting after extraction (visit 2) and until 14 days post extraction (Visit 3, 4, 5)]
• Possibility to prosthetically place an implant [Time frame: implant placement (Visit 7 - within 5 months from tooth extraction)]
• Peri-implant radiographic bone level changes [Time frame: at implant loading (visit 9 - within 5 months from implant placement) and at the end of the study (12 months post loading - visit 10)]
• Participants' satisfaction with treatment [Time frame: at the end of the study, 12 months post loading (Visit 10)]
• Implant torque [Time frame: Implant placement (visit 7 - within 5 months from tooth extraction)]

Eligibility criteria

Inclusion criteria

• ≥25-year-old males and females;
• good systemic health (self-assessment);
• presence of an unrestorable/hopeless tooth with periodontal attachment and buccal bone preserved at least for 2/3rd of the root and not associated with acute periapical pathology;
• full mouth bleeding and plaque scores ≤ 25%

Exclusion criteria

• uncontrolled or untreated periodontal disease;
• history of local (head and neck) radiation therapy in the past 5 years;
• acute endodontic lesion in the test tooth or in the neighbouring areas to the extraction procedure (sites with presence of an asymptomatic chronic lesion are eligible);
• medical history that includes uncontrolled diabetes or hepatic or renal disease, or other serious medical conditions that can impact on bone metabolism (e.g. rheumatoid arthritis, osteoporosis) or transmittable diseases (e.g. HIV-related disease);
• history of alcohol or drug abuse;
• smokers of ≥10 cigarettes a day;
• self-reported pregnancy or lactation.

Criteria are shown verbatim from the registry (in English). Final eligibility is always assessed by the study center.

Healthy volunteers: No

Study design

Allocation

Randomized

Model

Parallel assignment

Masking

Single blind

Primary purpose

Treatment

Study locations

Italy · 2 centers

• Centro di Odontoiatria, Dipartimento di Medicina e Chirurgia, Università di Parma — Parma
• Centro di Odontoiatria — Parma

Publications

• Guizzardi S, Galli C, Govoni P, Boratto R, Cattarini G, Martini D, Belletti S, Scandroglio R. Polydeoxyribonucleotide (PDRN) promotes human osteoblast proliferation: a new proposal for bone tissue repair. Life Sci. 2003 Aug 29;73(15):1973-83. doi: 10.1016/s0024-3205(03)00547-2. PMID 12899922
• Colangelo MT, Govoni P, Belletti S, Squadrito F, Guizzardi S, Galli C. Polynucleotide biogel enhances tissue repair, matrix deposition and organization. J Biol Regul Homeost Agents. 2021 Jan-Feb;35(1):355-362. doi: 10.23812/20-320-L. No abstract available. PMID 33480222
• Avila-Ortiz G, Chambrone L, Vignoletti F. Effect of alveolar ridge preservation interventions following tooth extraction: A systematic review and meta-analysis. J Clin Periodontol. 2019 Jun;46 Suppl 21:195-223. doi: 10.1111/jcpe.13057. PMID 30623987

Identifiers

NCT: NCT07099846 · P-005

Primary sources (government registries)

• ClinicalTrials.gov (US NIH)

View this study on ClinicalTrials.gov ↗