Use of Mesenchymal Stem Cells for Alveolar Bone Tissue Engineering for Cleft Lip and Palate Patients

• ClinicalTrials.gov Identifier: NCT01932164
• Recruitment Status: Completed
• First Posted: August 30, 2013
• Results First Posted: March 30, 2015
• Last Update Posted: May 28, 2020
• Sponsor: Hospital Sirio-Libanes
• Collaborator: Hospital Infantil Universitario Niño Jesús, Madrid, Spain
• Information provided by (Responsible Party): Daniela Franco Bueno, Hospital Sirio-Libanes

Tracking Information

• First Submitted Date: August 27, 2013
• First Posted Date: August 30, 2013
• Results First Submitted Date: March 18, 2015
• Results First Posted Date: March 30, 2015
• Last Update Posted Date: May 28, 2020
• Actual Study Start Date: May 2013
• Actual Primary Completion Date: December 16, 2015 (Final data collection date for primary outcome measure)

Current Primary Outcome Measures (submitted: March 18, 2015)

• Amount of New Bone Mass Formed [ Time Frame: 6 months from surgical procedure for alveolar grafting; ]
  The quantification of bone formation will be conducted by analysis of CT scans of alveolar cleft area that receive autogenous mesenchymal stem cells from dental pulp associated with the biomaterial 3 and 6 months after surgical procedure ( tissue engineering ) in comparison with CT Scan previously of tissue engineering surgery.Preoperative and follow-up examinations reveled progressive alveolar bone union in all patients. For these 5 patients final completion of the alveolar defect with an 89,5% mean bone height was detected 6 months postoperatively. We are still waiting the canine dental eruption at the new bone. For these group of patients the bone tissue engineering using autologous mesenchymal stem cells associated with biomaterial resulted in satisfactory bone healing.
• Quality of Bone Regeneration [ Time Frame: Three months after the graft ]
  The quality of bone formation will be conducted by analysis of CT scans of alveolar cleft area through canine tooth eruption in these position of new bone formation by tissue engineering techniques. We are waiting the canine eruption at the mouth.

Original Primary Outcome Measures (submitted: August 27, 2013)

• Amount of new bone mass formed [ Time Frame: 3 months from surgical procedure for alveolar grafting; ]
  The quantification of bone formation will be conducted by analysis of CT scans of alveolar cleft area that receive autogenous mesenchymal stem cells from dental pulp associated with the biomaterial 3 months from surgical procedure of tissue engineering.
• Quality of bone regeneration [ Time Frame: Three months after the graft ]
  The quality of bone formation will be conducted by analysis of CT scans of alveolar cleft area through canine tooth eruption in these position of new bone formation by tissue engineering techniques.

• Current Secondary Outcome Measures: Not Provided
• Original Secondary Outcome Measures: Not Provided
• Current Other Pre-specified Outcome Measures: Not Provided
• Original Other Pre-specified Outcome Measures: Not Provided

Descriptive Information

• Brief Title: Use of Mesenchymal Stem Cells for Alveolar Bone Tissue Engineering for Cleft Lip and Palate Patients
• Official Title: Use of Mesenchymal Stem Cells for Alveolar Bone Tissue Engineering for Cleft Lip and Palate Patients
• Brief Summary: The aim of this study is to perform the bone tissue engineering to reconstruct the alveolar bone defect in cleft lip and palate patients using mesenchymal stem cells from deciduous dental pulp associated with a collagen and hydroxyapatite biomaterial (Geistlich Bio-Oss®) through prospective qualitative and quantitative analysis of bone neoformation.

Detailed Description

The reconstruction of the craniofacial skeleton in development between 2 and 10 years old, remains a major challenge for reconstructive plastic surgery. Local autogenous bone is practically unavailable, the distant bone graft has significant morbidity and use of alloplastic materials is incompatible with the growing facial skeleton. With the advent of bioengineered tissue, however, osteogenesis induced by the use of mesenchymal stem cells associated with biomaterials has become a potential solution to the shortage bone-related morbidity and donor bone in the region in pediatric patients.

The association of mesenchymal stem cells to biomaterials has provided new bone formation and a significant reduction of morbidity, for rehabilitation of the alveolar bone in patients with cleft lip palate.

To perform the rehabilitation of alveolar bone cleft, other donor regions of bone (iliac crest, ribs, skull) suffer morbidity for obtaining bone to be used in alveolar bone grafting. In order to eliminate the morbidity at the bone donor region for these patients and reduce costs of patient permanence in the operating room the aim of this study is to perform the bone tissue engineering to reconstruct the alveolar bone defect in cleft lip and palate patients using mesenchymal stem cells from deciduous dental pulp associated with a collagen and hydroxyapatite biomaterial (Geistlich Bio-Oss®) through prospective qualitative and quantitative analysis of bone neoformation.

• Study Type: Interventional
• Study Phase: Not Applicable
• Study Design: Allocation: N/A; Intervention Model: Single Group Assignment; Masking: None (Open Label); Primary Purpose: Treatment
• Condition: Cleft Lip and Palate

Intervention

• Procedure: maxillary alveolar graft by tissue engineering
  Extraction of deciduous teeth of cleft lip and palate patients to obtain mesenchymal stem cells;
  Other Names:

  • alveolar bone graft
  • bone tissue engineering
  • bone tissue engineering using mesenchymal stem cells
• Procedure: Bone tissue engineering using mesenchymal stem cells
  Secondary alveolar graft in patients with cleft lip and palate using using mesenchymal stem cell obtained from dental pulp of deciduous teeth (autogenous) associated with a biomaterial composed of collagen and hydroxyapatite.

Study Arms

Experimental: cleft lip and palate

5 Patients with cleft unilateral lip and palate that have already performed the alignment of dental arches through the recommended orthodontic treatment will be selected to be submited to alveolar bone tissue engineering surgery

Interventions:

• Procedure: maxillary alveolar graft by tissue engineering
• Procedure: Bone tissue engineering using mesenchymal stem cells

Publications *

• Hibi H, Yamada Y, Ueda M, Endo Y. Alveolar cleft osteoplasty using tissue-engineered osteogenic material. Int J Oral Maxillofac Surg. 2006 Jun;35(6):551-5. doi: 10.1016/j.ijom.2005.12.007. Epub 2006 Apr 11.
• Gimbel M, Ashley RK, Sisodia M, Gabbay JS, Wasson KL, Heller J, Wilson L, Kawamoto HK, Bradley JP. Repair of alveolar cleft defects: reduced morbidity with bone marrow stem cells in a resorbable matrix. J Craniofac Surg. 2007 Jul;18(4):895-901. doi: 10.1097/scs.0b013e3180a771af.
• Tanikawa DYS, Pinheiro CCG, Almeida MCA, Oliveira CRGCM, Coudry RA, Rocha DL, Bueno DF. Deciduous Dental Pulp Stem Cells for Maxillary Alveolar Reconstruction in Cleft Lip and Palate Patients. Stem Cells Int. 2020 Mar 12;2020:6234167. doi: 10.1155/2020/6234167. eCollection 2020.

Recruitment Information

• Recruitment Status: Completed
• Actual Enrollment (submitted: August 27, 2013): 5
• Original Estimated Enrollment: Same as current
• Actual Study Completion Date: December 16, 2015
• Actual Primary Completion Date: December 16, 2015 (Final data collection date for primary outcome measure)

Eligibility Criteria

Inclusion Criteria:

• Diagnosis of unilateral cleft lip and palate ;
• Patient who has performed the treatment to align the dental arches in the ambulatory of odontology at Hospital Municipal Infantil Menino Jesus;
• Patient that have Goslow index 1, 2 or 3;
• Patiente which have 2/3 of the root of the canine tooth (cleft region) formed.

Exclusion Criteria:

• Prior alveolar surgery;
• Canine teeth erupted before the bone graft;
• Presence of co-morbidities;
• Incomplete documentation;
• Patients who have not done all the multidisciplinary treatment at Hospital Municipal Infantil Menino Jesus.

Sex/Gender

• Sexes Eligible for Study: All

• Ages: 7 Years to 12 Years (Child)
• Accepts Healthy Volunteers: No
• Contacts: Contact information is only displayed when the study is recruiting subjects
• Listed Location Countries: Brazil

Administrative Information

• NCT Number: NCT01932164
• Other Study ID Numbers: HSL 2013-04
• Has Data Monitoring Committee: Yes
• U.S. FDA-regulated Product: Not Provided
• IPD Sharing Statement: Not Provided
• Current Responsible Party: Daniela Franco Bueno, Hospital Sirio-Libanes
• Original Responsible Party: Same as current
• Current Study Sponsor: Hospital Sirio-Libanes
• Original Study Sponsor: Same as current
• Collaborators: Hospital Infantil Universitario Niño Jesús, Madrid, Spain

Investigators

• Principal Investigator: Daniela F Bueno, PhD; Hospital Sírio-Libanês

• PRS Account: Hospital Sirio-Libanes
• Verification Date: May 2020