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

NCT04998058 | Not Yet Recruiting Phase 1

• 1 other identifier: Bone Graft-Exosomes Project
• Study Type: interventional
• Target: 20
• Locations: 1 country
• Sites: 1

Brief Summary

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.

Conditions

Bone Loss, Osteoclastic; Bone Loss, Alveolar; Alveolar Bone Loss; Alveolar Bone Atrophy; Grafting Bone

Keywords

bone; bone formation; bone graft; tissue engineering; stem cell; exosome; cell-free therapy

Outcome Measures

Primary Outcomes (2)

• Assessment of changes in bone density and quantity

  Comparative analysis (test vs. control) of the changes in bone density and quantity by cone beam computed tomography (CBCT).

  0 (baseline), 90 and 180 days

• Assessment of bone quantity

  Histomorphometry analysis expressed in percentage of newly formed bone

  180 days

Secondary Outcomes (1)

• Presence of bone formation markers

  180 days

Other Outcomes (1)

• Assessment of bone substitute resorption rate

  180 days

Study Arms (2)

Control (conventional graft procedure), bone substitute and saline solution.

PLACEBO COMPARATOR

one randomly assigned maxillary sinus grafted internally defined as control (bone substitute + saline solution) per subject.

Procedure: Maxillary sinus floor elevation grafting with synthetic bone substitute.

Test (modified graft), bone substitute and concentrated culture medium (CM)

EXPERIMENTAL

one randomly assigned maxillary sinus grafted internally defined as test (bone substitute + concentrated culture medium) per subject.

Procedure: Maxillary sinus floor elevation grafting with synthetic bone substitute.

Interventions

Maxillary sinus floor elevation grafting with synthetic bone substitute. PROCEDURE

Bone augmentation at the floor of the maxillary sinus with bone substitutes.

Also known as: Maxillary sinus lift bone grafting

Control (conventional graft procedure), bone substitute and saline solution.; Test (modified graft), bone substitute and concentrated culture medium (CM)

Eligibility Criteria

• Age: 35 Years+
• Sex: all
• Healthy Volunteers: Yes
• Age Groups: Adult (18-64), Older Adult (65+)

You may qualify if:

• patients \>35 years-old.
• presenting highly atrophic fully edentulous maxilla (residual bone height \<5 mm).
• In need of bilateral sinus floor augmentation aiming full mouth implant-supported rehabilitation.
• having teeth extraction at least 8 weeks prior to bone augmentation.

You may not qualify if:

• smokers, illicit drug users and alcohol daily consumers.
• patients with metabolic and/or systemic diseases leading to impaired healing (e.g. decompensated diabetes, leukocyte or coagulation disorders, immunosuppression).
• history of radiotherapy in the head or neck region.
• bisphosphonate-based therapy recipients.
• intolerant to general/local anesthesia.

Sponsors & Collaborators

• Pontificia Universidade Católica do Rio Grande do Sul: lead
• ITI International Team for Implantology, Switzerland: collaborator
• KU Leuven: collaborator
• Rio Grande do Sul Brain Institute (InsCer): collaborator

Study Sites (1)

Pontificia Universidade Católica do Rio Grande do Sul

Porto Alegre, Rio Grande do Sul, 90619-900, Brazil

Location

Related Publications (3)

• Cabreira CL, Fulginiti RL, Sesterheim P, Shinkai RSA, Teixeira ER. Effect of hyaluronic acid on paracrine signaling of osteoblasts from mesenchymal stromal cells: potential impact on bone regeneration. Clin Oral Investig. 2021 Jul;25(7):4571-4578. doi: 10.1007/s00784-020-03771-x. Epub 2021 Jan 7.

  PMID: 33410999 BACKGROUND

• Teixeira ER, Boeckel D, Fulginiti R L, Shinkai R S A, Machado D. Mesenchymal stem cells and hyaluronic acid for bone grafting. Clinical Oral Implants Research, 2018, (29), 55-55.

  BACKGROUND

• Boeckel DG, Sesterheim P, Peres TR, Augustin AH, Wartchow KM, Machado DC, Fritscher GG, Teixeira ER. Adipogenic Mesenchymal Stem Cells and Hyaluronic Acid as a Cellular Compound for Bone Tissue Engineering. J Craniofac Surg. 2019 May/Jun;30(3):777-783. doi: 10.1097/SCS.0000000000005392.

  PMID: 30865107 BACKGROUND

MeSH Terms

Conditions

Bone Resorption; Alveolar Bone Loss

Condition Hierarchy (Ancestors)

Bone Diseases; Musculoskeletal Diseases; Periodontal Atrophy; Periodontal Diseases; Mouth Diseases; Stomatognathic Diseases

Study Officials

• Eduardo R Teixeira, DDS, Ph.D.

  Pontificia Universidade Católica do Rio Grande do Sul

  PRINCIPAL INVESTIGATOR

• Denise C Machado, MSc., Ph.D.

  Pontificia Universidade Católica do Rio Grande do Sul

  STUDY CHAIR

• Rogerio B Oliveira, DDS, Ph.D.

  Pontificia Universidade Católica do Rio Grande do Sul

  STUDY CHAIR

• Rosemary A Shinkai, DDS, Ph.D.

  Pontificia Universidade Católica do Rio Grande do Sul

  STUDY CHAIR

• Patricia Sesterheim, MSc, Ph.D.

  Institute of Cardiology of Rio Grande do Sul

  STUDY CHAIR

• Reinhilde Jacobs, DDS, Ph.D.

  KU Leuven

  STUDY CHAIR

Central Study Contacts

Eduardo R Teixeira, DDS, Ph.D.

CONTACT

+555133203562; eduardo.teixeira@pucrs.br

Rosemay A Shinkai, DDS, Ph.D.

CONTACT

+555133203562; rshinkai@pucrs.br

Study Design

• Study Type: interventional
• Phase: phase 1
• Allocation: RANDOMIZED
• Masking: DOUBLE
• Who Masked: PARTICIPANT, OUTCOMES ASSESSOR
• Masking Details: Bone tissue samples and image data allocation identified only by sequential numbers, not by name, for the outcome assessor.
• Purpose: OTHER
• Intervention Model: PARALLEL
• Sponsor Type: OTHER
• Responsible Party: PRINCIPAL INVESTIGATOR
• PI Title: DDS, Ph. D., Prof. Dr.

Model Details: Double-blind, randomized controlled clinical trial, intra-individual (split-mouth design).

Study Record Dates

• First Submitted: July 23, 2021
• First Posted: August 10, 2021
• Study Start: December 15, 2025
• Primary Completion (Estimated): August 30, 2026
• Study Completion (Estimated): December 30, 2026
• Last Updated: June 5, 2025

Record last verified: 2025-06

Data Sharing

• IPD Sharing: Will not share

Locations

BR (1)