Pilot Study on the Effectiveness of a Flexible Hydroxyapatite-Based Composite for Jaw Bone Regeneration

Following a review of the scientific literature, it was found that there are no clinical studies but only in vitro and in vivo studies, which show promising results in terms of bone formation and integration. However, it is necessary to evaluate how well the regenerated bone maintains its structural integrity over time, considering masticatory function and biomechanics in real-life scenarios. Factors such as mechanical load, remodeling dynamics, and interactions with surrounding tissues could influence the long-term stability of the regenerated bone. Additionally, another important aspect to study is the potential complications and adverse effects associated with the use of the flexible HAp-based composite.

Study Objectives The primary objective is to evaluate the efficacy in terms of regenerated bone volume using the new flexible HAp-based composite in mixed bone defects of the jawbones.

Primary Outcome Measures The volume of regenerated bone will be measured using CBCT scans before device placement, immediately after the surgical procedure, and at 8 months post-procedure. The percentage of regenerated bone obtained compared to the initially planned augmentation, i.e., the mean volume difference, will be calculated before the surgical procedure, immediately after device placement, and at 8 months.

Secondary Objectives These include evaluating intraoperative and postoperative complications occurring at the time of placement or after device placement, assessing the conditions of peri-implant hard and soft tissues, measuring overall patient satisfaction with the treatment, analyzing the correlation between implant survival and various systemic and clinical patient factors, and conducting a histological evaluation of vascularization and new bone formation in samples of regenerated bone taken during implant site preparation.

Secondary Outcome Measures The condition of hard tissues will be assessed based on periapical intraoral radiographs. For soft tissue conditions, for each implant site, peri-implant probing depth (PPD), bleeding on probing (BOP), presence of peri-implant plaque (mPLI), and the amount of keratinized gingiva will be considered at m3, m6, m9, and m12 from implant placement. Any pathological events such as neurological lesions, exposures, infections, inflammation, fractures, or loosening of prosthetic screws, and prosthesis fractures reported in the clinical record during or after device placement and throughout the clinical follow-up will be evaluated as outcomes of intraoperative and postoperative complications at m3, m6, m9, and m12 from device placement. To evaluate overall patient satisfaction, two validated questionnaires will be analyzed: the Oral Health Impact Profile (OHIP-14) and a Patient Satisfaction questionnaire. To assess the correlation between implant survival and certain systemic and clinical patient factors, the following independent variables will be studied: age, gender, smoking status, jaw in which the implants were placed, type of implant, implant length, implant diameter, and compared with implant survival data. Histological and histomorphometric analysis will be conducted on samples of regenerated bone collected during implant site preparation at the passage of the first preparation drill.

Study Plan A total of 20 patients will be included in the study.

Study Design This is a spontaneous, prospective, interventional clinical investigation with post-marketing medical device analysis, enrolling patients with jaw bone atrophy at the Oral Surgery Unit of the Dental Clinic, University of Bologna. Collaboration with the laboratory at the University of Chieti-Pescara, Department of Medical, Oral, and Biotechnological Sciences, is planned. Insurance will be covered by university funds for Oral Surgery.

Study Start Date/Enrollment: After Ethics Committee approval and obtaining corporate clearance Prospective Period: 1 year Total Study Duration: 5 years (including individual follow-ups and data processing)

Study Population Inclusion Criteria Patients with partially edentulous and atrophic jaws, requiring implant-prosthetic rehabilitation (from 1 to 3 implants), classified as Seibert Class II or III, and needing a GBR bone regeneration intervention with defects not exceeding 7 mm in height. Patients must be 18 years or older and must provide informed consent.

Exclusion Criteria General contraindications to implant surgery. Patients who have received head and neck irradiation of more than 70 Gray. Immunocompromised and immunosuppressed patients. Patients treated or under treatment with intravenous amino-bisphosphonates. Patients with poor oral hygiene and motivation. Uncontrolled diabetes. Pregnancy or breastfeeding. Drug or alcohol dependency. Psychiatric conditions that contraindicate surgical treatment. Limited mouth opening (less than 3.5 cm between the two arches in the anterior region). Patients with acute or chronic inflammation/infection at the implant site. Patients referred solely for implant placement.

Medical Device Under Study The study focuses on a bio-composite bone substitute based on hydroxyapatite (Flexi-Oss, Medical Inventi S.A., Lublin, Poland). This is a biphasic material comprising hydroxyapatite and a polymer component.

Statistical Methods Sample Size The mean regenerated bone volume using a semi-occlusive CAD/CAM titanium device from a previous study was 1524 mm³. Considering an estimate of 1380 mm³ of regenerated bone using the hydroxyapatite-based bio-composite bone substitute, with a standard deviation of 200 mm³, a significance level (alpha) of 0.05, and a statistical power of 80%, using the two-sided Z test, it was determined that 16 patients need to be enrolled. Considering a potential dropout rate of 20%, the number of patients to be included in the study has been increased to 20.