Safety and Efficacy of Bone Bioengineering Kit With Stem Cells for Alveolar Cleft Repair

Phase III Randomized Clinical Trial on the Use of a Bone Bioengineering Kit With Stem Cells Versus Autogenous Iliac Crest Graft for Alveolar Cleft Repair in Patients With Cleft Lip and Palate

The objective of this study is to compare the safety and efficacy of a bone tissue engineering kit - composed of 10⁶ autologous mesenchymal stem cells derived from deciduous dental pulp combined with Bio-Oss® Collagen - with secondary autogenous iliac crest bone grafting for alveolar cleft reconstruction in patients with cleft lip and palate.

Individuals aged 7 to 12 years with unilateral pre-foramen or transforamen cleft lip and palate who require secondary alveolar bone grafting and have previously cryopreserved autologous deciduous dental pulp-derived mesenchymal stem cells will be eligible for inclusion.

The study will be conducted in two stages. Stage 1 is a prospective, single-arm study designed to evaluate the initial safety of the investigational product, with primary endpoints consisting of the incidence of procedure-related adverse events and postoperative pain until hospital discharge. Stage 2 is a prospective, randomized, assessor-blinded clinical trial comparing the bone tissue engineering kit with standard autogenous iliac crest bone grafting. The co-primary endpoints are the success rate of alveolar reconstruction, defined as ≥70% bone fill of the alveolar cleft measured by volumetric computed tomography 12 months after surgery, and the incidence of procedure-related adverse events.

Inclusion Criteria:

• Written Informed Consent Form (ICF) signed by the participant's legally authorized representative.
• Written Assent Form signed by the participant.
• Patients aged 7 to 12 years at the time of secondary alveolar bone graft surgery.
• Patients diagnosed with unilateral pre-foramen or transforamen cleft lip and palate.
• Availability of autologous mesenchymal stem cells derived from deciduous dental pulp, previously stored in a biobank before signing the Informed Consent Form (ICF).
• Patients with a maxillary arch previously aligned through orthodontic treatment and considered suitable for alveolar bone grafting.
• Medically fit to undergo the surgical procedure, as determined by the responsible clinical team.
• Complete and up-to-date vaccination schedule according to the Brazilian National Immunization Program (PNI).
• Participants and their legal representatives are considered reliable, willing to comply with the study procedures, attend all required study visits, and remain available throughout the study period.

Exclusion Criteria:

• Previous surgery for alveolar cleft repair.
• Known allergy to latex gloves or suture materials (Catgut, Vicryl, Monocryl, Nylon, Polyester, or Polypropylene).
• Uncontrolled systemic diseases or other clinical conditions that may increase surgical risk or interfere with bone healing, including, but not limited to, uncontrolled diabetes mellitus, clinically significant cardiovascular disease, or other conditions deemed relevant by the investigator.
• Metabolic bone diseases or other conditions that may impair bone formation or healing.
• Congenital or acquired immunosuppression, or use of immunosuppressive medications that may interfere with healing or treatment response.
• History of radiotherapy or chemotherapy involving the head and neck region, when applicable, or any other condition that may compromise bone repair.
• Presence of palatal fistulas resulting from previous surgeries.
• Incomplete orthodontic or computed tomography documentation.
• Eruption of the permanent canine before signing the Informed Consent Form (ICF) and Assent Form, and before secondary alveolar bone graft surgery.
• Participants who are pregnant or breastfeeding at the time of screening or during the study.
• Presence of systemic infection, active infection of the oral cavity or surgical site, or any infectious condition that, in the investigator's opinion, may compromise participant safety or the study outcomes.
• Inability to obtain or release the investigational product due to failure in cell processing or failure to meet the established quality control criteria.
• Concurrent participation in another interventional clinical trial or previous participation in a study that, in the investigator's judgment, may interfere with the results of the present study.
• Any other condition that, in the opinion of the investigator or designee, may preclude informed consent, pose an unacceptable risk to the participant, compromise protocol compliance, interfere with endpoint assessment, or otherwise jeopardize the objectives of the study.