Effectiveness and Safety of Method of Maxilla Alveolar Process Reconstruction Using Synthetic Tricalcium Phosphate and Autologous MMSCs

Study Overview
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Brief Summary
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Autologous MMSCs will be isolated from oral mucosa biopsy sample and expanded in vitro.Tissue engineered construction will be created using synthetic tricalcium phosphate and autologous MMSCs. Patients will undergo sinus lift procedure with implantation of created tissue-engineered construction. This is a single arm study with no control. All patients receive cell therapy.

Detailed Description
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Patients with verified diagnosis partially edentulous maxilla and alveolar bone atrophy will undergo oral mucosa biopsy and autologous MMSCs will be derived and expanded in vitro during 3-4 weeks. After that tissue engineered construction will be created using synthetic tricalcium phosphate and autologous MMSCs. Patients will undergo sinus lift procedure with implantation of created tissue-engineered construction. Six months later patients will undergo dental implant installation. Biopsy of bone tissue at the site of sinus lift will be performed as a part of dental implant installation with subsequent histological analysis of bone specimen.

Official Title
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Effectiveness and Safety of Method of Maxilla Alveolar Process Reconstruction Using Tissue Engineered Construction Based on a Synthetic Tricalcium Phosphate and Autologous Multipotent Mesenchymal Stromal Cells Obtained From Oral Mucosa

Conditions
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Partially Edentulous Maxilla, Alveolar Bone Atrophy, Alveolar Bone Loss

Intervention / Treatment
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* Procedure: Oral mucosa biopsy
* Procedure: Sinus lift with implantation of tissue engineered construction
* Device: Dental implant


Participation Criteria
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Eligibility Criteria
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Inclusion Criteria: Partially edentulous maxilla Height of the bone tissue in the area of reconstruction 1 - 5 mm according to results of cone-beam computed tomography Minimal height of the augmentation - 8 mm Volume of bone tissue deficiency of the alveolar process of the maxilla 3 - 5 cm3 Implant installation scheduled to be at least 6 months after sinus-lift operation Patient is familiar with Participant information sheet Patient signed informed consent form Non-inclusion Criteria: Chronic and acute ear, nose and throat diseases, including maxillary sinusitis, foreign bodies in the maxillary sinus, odontogenic and not odontogenic maxillary sinus cyst Medical history of surgery on maxillary sinuses during preceding 6 months prior to implantation of tissue engineered construction Progressive somatic disease (clinically significant diseases of the cardiovascular, hematopoietic or endocrine system, systemic diseases, immunopathological states) Patients with malignant tumors including postoperative period, patients receiving chemotherapy and/or radiotherapy Any conditions limiting compliance (dementia, neuropsychiatric disease, drug and alcohol abuse etc.) Significant weight loss (> 10% of body weight in the previous year) of unknown etiology Patient prescribed for any medications with proven effect on bone metabolism Diabetes mellitus, disorders of thyroid and parathyroid glands Clinically significant abnormalities in results of laboratory tests Participation in other clinical trials (or administration of investigational drugs) during 3 months prior inclusion Exclusion Criteria: Patient's refusal from the further participation in trial Patient's refusal from compliance with the requirements of contraception during the participation in research Plaque index (PI)> 15% Sulcus bleeding index (SBI) > 10% Chronic kidney disease IV - V stages (creatinine clearance < 30 mL/min estimated by Cockroft-Gault formula) Confirmed syphilis, HIV, hepatitis B or C infections Dropout Criteria: Perforation of the Schneider's membrane more than 5 mm on the stage of the sinus-lift operation Pregnancy

Ages Eligible for Study
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Minimum Age: 20 Years
Maximum Age: 60 Years

Sexes Eligible for Study
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All

Accepts Healthy Volunteers
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No

Study Plan
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How is the study designed?
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Design Details

Primary Purpose: Treatment
Intervention Model: Single Group Assignment
Masking: None (Open Label)


Arms and Interventions

| Participant Group/Arm | Intervention/Treatment |
| --- | --- |
| Experimental: Tissue engineered construction implantation<br> | Procedure: Oral mucosa biopsy<br> <br> Procedure: Sinus lift with implantation of tissue engineered construction<br> <br> Device: Dental implant<br> <br> |

What is the study measuring?
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Primary Outcome Measures

| Outcome Measure | Measure Description | Time Frame |
| --- | --- | --- |
| Number of serious adverse events (SAEs) and serious adverse reactions (SARs) |  | 1 week after treatment | 

Secondary Outcome Measures

| Outcome Measure | Measure Description | Time Frame |
| --- | --- | --- |
| Quality of life monitoring | Quality of life estimated by validated questionnaire: the Short Form (36) Health Survey (SF-36). | up to 24 weeks after treatment | 
| Changes in bone tissue volume | Changes in volume and density of bone tissue at the site of manipulation and newly formed bone micro-architecture assessed by cone beam CT (morphometrical analysis using Hounsfield unit measurements) | up to 24 weeks after treatment | 
| Correlation of morphometrical analysis using cone beam CT scan with absolute value of the newly formed bone | Biopsy of bone tissue at the site of sinus lift will be performed as a part of dental implant installation. Bone sample will be evaluated histologically: absolute value of the newly formed bone will be calculated using histomorphometrical analysis. | 24 weeks after treatment | 

 Terms related to the study
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Keywords Provided by Centre Hospitalier Valida
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Alveolar Bone Loss, Alveolar Bone Atrophy, Dental Implantation, Bone Tissue Reconstruction, Sinus Lift, Autologous Multipotent Mesenchymal Stem Cell, Autologous MMSCs, Synthetic Tricalcium Phosphate, Tissue Engineered Construction, Oral Mucosa