NCT04998058

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

Not yet recruiting Phase 1, PHASE2 Last updated 5 June 2025

What this trial tests

Phase 1, PHASE2 trial testing Maxillary sinus floor elevation grafting with synthetic bone substitute. in Bone Loss, Osteoclastic in 20 participants. Not yet recruiting.

Timeline

15 December 2025

Primary endpoint
30 August 2026

30 December 2026

Quick facts

Lead sponsor	Pontificia Universidade Católica do Rio Grande do Sul
Phase	Phase 1, PHASE2
Status	Not yet recruiting
Study type	INTERVENTIONAL
Allocation	randomized
Design	parallel
Masking	double
Primary purpose	other
Enrollment	20
Start date	15 December 2025
Primary completion	30 August 2026
Estimated completion	30 December 2026
Sites	1 location across Brazil

Drugs / interventions tested

• Maxillary sinus floor elevation grafting with synthetic bone substitute.

Conditions studied

• Bone Loss, Osteoclastic — all drugs for Bone Loss, Osteoclastic →
• Bone Loss, Alveolar — all drugs for Bone Loss, Alveolar →
• Alveolar Bone Loss — all drugs for Alveolar Bone Loss →
• Alveolar Bone Atrophy — all drugs for Alveolar Bone Atrophy →

Sponsor

Pontificia Universidade Católica do Rio Grande do Sul — full company profile →

Who can join

35 and older, any sex, with Bone Loss, Osteoclastic or Bone Loss, Alveolar. Patients with the condition only — healthy volunteers not accepted.

Sponsor's own description

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.

Publications & conference data

8 peer-reviewed publications reference this trial (live from Europe PMC):

1. Clinical applications of stem cell-derived exosomes.
   Tan F, Li X, Wang Z, Li J, et al · · 2024 · cited 390× · PMID 38212307 · DOI 10.1038/s41392-023-01704-0
2. Insight into the Functional Dynamics and Challenges of Exosomes in Pharmaceutical Innovation and Precision Medicine.
   Sharma A, Yadav A, Nandy A, Ghatak S. · · 2024 · cited 40× · PMID 38931833 · DOI 10.3390/pharmaceutics16060709
3. The Potential of MSC-Based Cell-Free Therapy in Wound Healing-A Thorough Literature Review.
   Ma H, Siu WS, Leung PC. · · 2023 · cited 39× · PMID 37298306 · DOI 10.3390/ijms24119356
4. Mesenchymal stem cell-derived extracellular vesicles: a regulator and carrier for targeting bone-related diseases.
   Tang J, Wang X, Lin X, Wu C. · · 2024 · cited 35× · PMID 38697996 · DOI 10.1038/s41420-024-01973-w
5. Understanding molecular characteristics of extracellular vesicles derived from different types of mesenchymal stem cells for therapeutic translation.
   Ding Z, Greenberg ZF, Serafim MF, Ali S, et al · · 2024 · cited 34× · PMID 38957857 · DOI 10.1016/j.vesic.2024.100034
6. Mesenchymal Stem Cell-Derived Extracellular Vesicle: A Promising Alternative Therapy for Osteoporosis.
   Lu CH, Chen YA, Ke CC, Liu RS. · · 2021 · cited 25× · PMID 34884554 · DOI 10.3390/ijms222312750
7. Extracellular Vesicles in Therapeutics: A Comprehensive Review on Applications, Challenges, and Clinical Progress.
   Goo J, Lee Y, Lee J, Kim IS, et al · · 2024 · cited 23× · PMID 38543204 · DOI 10.3390/pharmaceutics16030311
8. Bone Regeneration with Mesenchymal Stem Cells in Scaffolds: Systematic Review of Human Clinical Trials.
   Theodosaki AM, Tzemi M, Galanis N, Bakopoulou A, et al · · 2024 · cited 17× · PMID 38407793 · DOI 10.1007/s12015-024-10696-5