Autogenous Mesenchymal Stem Cell Culture-Derived Signalling Molecules as Enhancers of Bone Formation in Bone Grafting

This study aims to evaluate bone formation in grafts in terms of its quality (density), quantity (volume) and maturation obtained with the application of a tissue-engineered bone grafting compound containing concentrated autogenous cell-culture medium (CM) and a synthetic bone substitute. The present study was designed as an experimental prospective split-mouth randomized controlled clinical trial. After protocol approval by the Research Ethics Committee, a total of 20 consecutive participants in need of maxillary reconstruction aiming implant-supported oral rehabilitation will be invited to join the study. To collect autogenous adipose tissue-derived mesenchymal stem cells (hASCs), an outpatient lipoplasty procedure at the abdominal area of each patient will be performed. To isolate and expand hASCs from the lipoaspirate, specific cell culture protocols will be followed, resulting in cultured viable cells and their conditioned medium (CM). Cells and CM will be then separated by a sequence of filters and centrifugation, and isolated CM will be frozen. ELISA will analyze the presence of chemokines and their concentration in CM before grafting. Following pre-op surgical planning, both maxillary sinuses of each patient will be grafted internally applying a lateral window to each sinus. The bony floor of the test maxillary sinus will be augmented with synthetic bone substitute (BoneCeramic™ 1-2 mm) mixed with 10 to 15 ml of CM (test). The control site will receive bone substitute with saline. Lateral windows in both sinuses will be then closed with a collagen membrane (Bio-Gide™). After 6 months, first-stage implant surgery will be performed placing 6 implants in each patient. Registration of implant stability by manual torque wrench will be performed. Also, bone biopsies from each drilled implant site will be collected for histology, histomorphometry and immunohistochemistry (RT-PCR). Tomographic evaluation of the bone formation will include cone beam computed tomographies (CBCTs) at pre-operative \[Baseline\], 90 \[T1\] and 180 \[T2 = implant placement\] days for bone 3D image analysis.

NCT Number	NCT04998058
Lead Sponsor	Pontificia Universidade Católica do Rio Grande do Sul Collaborators: ITI International Team for Implantology, Switzerland, KU Leuven, Rio Grande do Sul Brain Institute (InsCer)
Conditions	Bone Loss, Osteoclastic, Bone Loss, Alveolar, Alveolar Bone Loss, Alveolar Bone Atrophy, Grafting Bone
Enrollment	20 participants
Start Date	2025-12-15
Primary Completion	2026-08-30 (estimated)
Study Completion	2026-12-30 (estimated)
Updated on ClinicalTrials.gov	2025-06-05