Bone Marrow Mononuclear Cells for the Repair of Severe Maxillofacial Bone Defects
A Clinical Study of Autologous Bone Marrow Mononuclear Cells Combined With Bio-oss® for the Repair of Severe Maxillofacial Bone Defects
This is a single-center, single-arm, open-label clinical study conducted at the Department of Stomatology, Nanjing Drum Tower Hospital. The study aims to evaluate the safety and efficacy of autologous bone marrow-derived mononuclear cells (BMMNCs) combined with a bone graft material (Bio-Oss) for the repair of severe maxillofacial (alveolar/jaw) bone defects caused by inflammation, trauma, or other reasons.
Approximately 20 patients aged 18-60 years with severe alveolar bone resorption requiring bone grafting will be enrolled. About 60 mL of autologous bone marrow will be aspirated from the iliac crest, and BMMNCs will be isolated by density-gradient centrifugation under GMP conditions without in vitro expansion. The BMMNCs will be mixed with Bio-Oss bone graft material and implanted into the bone defect, covered with a collagen membrane. Cone-beam CT (CBCT) will be performed postoperatively to assess new bone formation. Follow-up visits are scheduled at 1 week, 1 month, 3 months, and 6 months after surgery. The primary outcome is the new bone volume fraction in the grafted area measured by CBCT. Safety will be assessed by clinical examination of the implantation site and laboratory tests (blood routine, urinalysis, liver and kidney function, blood glucose).
Обзор исследования
Статус
Подробное описание
Severe maxillofacial bone defects caused by trauma, tumor resection, congenital diseases (e.g., cleft lip and palate), or severe periodontitis-related alveolar bone resorption remain a major clinical challenge. Conventional bone grafting approaches (autologous bone, allogeneic bone, xenogeneic bone substitutes) have limitations including limited bone volume, additional donor-site morbidity, immune rejection, and unpredictable graft resorption.
Bone marrow-derived mononuclear cells (BMMNCs) contain hematopoietic stem cells, mesenchymal stem cells, and other progenitor populations with osteogenic and regenerative potential. Unlike mesenchymal stem cell-based approaches, BMMNCs can be used directly without in vitro expansion, shortening the treatment cycle and reducing cost and biosafety risks.
In this study, eligible patients will undergo the following procedure under local anesthesia: the mucoperiosteum at the defect site is incised and reflected, fibrous connective tissue is removed, and nourishing holes are prepared with a turbine drill. Approximately 60 mL of autologous bone marrow is aspirated from the iliac crest; BMMNCs are isolated using human peripheral blood lymphocyte separation medium by density-gradient centrifugation in a GMP-grade cell preparation facility, with quality control testing. The freshly prepared BMMNCs are mixed with an appropriate amount of Bio-Oss bone graft material, implanted into the defect, covered with a collagen membrane, and the wound is sutured. Perioperative antibiotics are routinely used.
CBCT scans are obtained immediately after surgery and at 3 and 6 months to measure the new bone volume fraction in the grafted area. If bone formation is adequate at 6 months, dental implant placement may be performed in the edentulous area. Clinical symptoms and signs are assessed immediately after surgery and at 1 week, 1 month, 3 months, and 6 months. Laboratory safety tests (complete blood count, urinalysis, liver and kidney function, blood glucose) are performed preoperatively and at postoperative follow-up visits. Adverse events are recorded and graded according to CTCAE from enrollment to the end of the study.
Тип исследования
Регистрация (Оцененный)
Фаза
- Непригодный
Контакты и местонахождение
Контакты исследования
- Имя: Dongyu Bao
- Номер телефона: 15651989007
- Электронная почта: baodongyu_anson@163.com
Места учебы
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Jiangsu
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Nanjing, Jiangsu, Китай, 210008
- Рекрутинг
- Nanjing Drum Tower Hospital, Nanjing University Medical School
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Критерии участия
Критерии приемлемости
Возраст, подходящий для обучения
Принимает здоровых добровольцев
Полы, имеющие право на обучение
Описание
Inclusion Criteria:
- Patients with severe alveolar bone resorption caused by inflammation, trauma, or other reasons, requiring bone grafting;
- Aged 18 to 60 years;
- No systemic diseases such as hypertension, diabetes, heart disease, or immunodeficiency;
- Fully informed of the entire study process, willing to participate, and able to sign the informed consent form.
Exclusion Criteria:
- Patients without maxillofacial bone defects;
- Patients with systemic diseases such as hypertension, heart disease, or diabetes;
- Patients who have recently received immunosuppressive therapy;
- Women who are planning pregnancy, pregnant, or breastfeeding;
- Patients with allergic constitution or a history of allergy to drugs or food;
- Patients with poor oral hygiene habits who cannot comply with medical advice, which may affect efficacy assessment;
- Patients who have participated in other clinical trials within the past 4 weeks.
Учебный план
Как устроено исследование?
Детали дизайна
- Основная цель: Уход
- Распределение: Н/Д
- Интервенционная модель: Одногрупповое задание
- Маскировка: Нет (открытая этикетка)
Оружие и интервенции
Группа участников / Армия |
Вмешательство/лечение |
|---|---|
|
Экспериментальный: Autologous BMMNCs + Bio-Oss bone graft
Patients receive transplantation of autologous bone marrow-derived mononuclear cells (BMMNCs) mixed with Bio-Oss bone graft material into the maxillofacial/alveolar bone defect, covered with a collagen membrane. Bone marrow (approximately 60 mL) is aspirated from the iliac crest; BMMNCs are isolated by density-gradient centrifugation without in vitro expansion. |
Approximately 60 mL of autologous bone marrow is aspirated from the iliac crest. BMMNCs are isolated using human peripheral blood lymphocyte separation medium by density-gradient centrifugation under GMP conditions, with quality control testing, and used fresh without in vitro expansion. The BMMNCs are mixed with an appropriate amount of Bio-Oss bone graft material and implanted into the bone defect during surgery under local anesthesia, covered with a collagen membrane. Perioperative antibiotics are routinely administered.
Другие имена:
Bio-Oss xenogeneic bone graft material mixed with BMMNCs and implanted into the defect; the graft is covered with a collagen membrane. |
Что измеряет исследование?
Первичные показатели результатов
Мера результата |
Мера Описание |
Временное ограничение |
|---|---|---|
|
New bone volume fraction in the grafted bone defect area measured by CBCT
Временное ограничение: Immediately after surgery, 3 months, and 6 months after surgery (primary assessment at 6 months)
|
The volume fraction of newly formed bone in the grafted defect area, measured and analyzed on cone-beam computed tomography (CBCT) images and reported as a percentage of new bone volume relative to the total grafted defect volume. |
Immediately after surgery, 3 months, and 6 months after surgery (primary assessment at 6 months)
|
Вторичные показатели результатов
Мера результата |
Мера Описание |
Временное ограничение |
|---|---|---|
|
Pain intensity assessed by Visual Analog Scale (VAS)
Временное ограничение: Immediately after surgery, 1 week, 1 month, 3 months, and 6 months after surgery
|
Pain at the surgical site assessed using the Visual Analog Scale (VAS), a 0-10 scale where 0 = no pain and 10 = worst imaginable pain. Higher scores indicate a worse outcome (more pain). |
Immediately after surgery, 1 week, 1 month, 3 months, and 6 months after surgery
|
|
Number of participants reporting good comfort without foreign body sensation
Временное ограничение: Up to 6 months after surgery
|
Patient self-reported comfort and absence of foreign body sensation, assessed by patient interview at each follow-up visit. Reported as the number of participants reporting good comfort. |
Up to 6 months after surgery
|
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Number of participants with complications requiring clinical management
Временное ограничение: Up to 6 months after surgery
|
Occurrence of persistent or irreversible symptoms and complications/comorbidities requiring clinical management, assessed at each follow-up visit. Reported as the number of participants with such events. |
Up to 6 months after surgery
|
Другие показатели результатов
Мера результата |
Мера Описание |
Временное ограничение |
|---|---|---|
|
Number of participants with abnormal mucosa at the implantation site
Временное ограничение: 1 week, 1 month, 3 months, and 6 months after surgery
|
Clinical examination of the color, shape, and texture of the mucosa at the implantation site, documented by photography. Reported as the number of participants with any abnormal mucosal finding. |
1 week, 1 month, 3 months, and 6 months after surgery
|
|
Number of participants with implant exposure
Временное ограничение: 1 week, 1 month, 3 months, and 6 months after surgery
|
Exposure of the implanted graft material at the implantation site, assessed by clinical examination and documented by photography. Reported as the number of participants with implant exposure. |
1 week, 1 month, 3 months, and 6 months after surgery
|
|
Number of participants with clinically significant abnormal laboratory safety tests
Временное ограничение: Preoperatively and at 1 week, 1 month, 3 months, and 6 months after surgery
|
Laboratory safety assessments include complete blood count, urinalysis, liver and kidney function, and blood glucose. Results will be aggregated and reported as the number of participants with any clinically significant laboratory abnormality. |
Preoperatively and at 1 week, 1 month, 3 months, and 6 months after surgery
|
|
Incidence and severity of adverse events
Временное ограничение: From enrollment to 6 months after surgery
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All adverse events recorded from enrollment to end of study, graded according to the Common Terminology Criteria for Adverse Events (CTCAE) on a 5-grade scale: Grade 1 = mild, Grade 2 = moderate, Grade 3 = severe, Grade 4 = life-threatening or disabling, Grade 5 = death. Higher grades indicate a worse outcome. Reported as the number of participants with adverse events. |
From enrollment to 6 months after surgery
|
Соавторы и исследователи
Следователи
- Главный следователь: Haiyan Qin, MD, Nanjing Drum Tower Hospital, Nanjing University Medical School
Публикации и полезные ссылки
Общие публикации
- 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.
- Kaigler D, Pagni G, Park CH, Braun TM, Holman LA, Yi E, Tarle SA, Bartel RL, Giannobile WV. Stem cell therapy for craniofacial bone regeneration: a randomized, controlled feasibility trial. Cell Transplant. 2013;22(5):767-77. doi: 10.3727/096368912X652968.
- Roddy E, DeBaun MR, Daoud-Gray A, Yang YP, Gardner MJ. Treatment of critical-sized bone defects: clinical and tissue engineering perspectives. Eur J Orthop Surg Traumatol. 2018 Apr;28(3):351-362. doi: 10.1007/s00590-017-2063-0. Epub 2017 Oct 28.
Даты записи исследования
Изучение основных дат
Начало исследования (Действительный)
Первичное завершение (Оцененный)
Завершение исследования (Оцененный)
Даты регистрации исследования
Первый отправленный
Впервые представлено, что соответствует критериям контроля качества
Первый опубликованный (Действительный)
Обновления учебных записей
Последнее опубликованное обновление (Действительный)
Последнее отправленное обновление, отвечающее критериям контроля качества
Последняя проверка
Дополнительная информация
Термины, связанные с этим исследованием
Ключевые слова
Дополнительные соответствующие термины MeSH
Другие идентификационные номера исследования
- 2022-LCYJ-ZX-07
Планирование данных отдельных участников (IPD)
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Информация о лекарствах и устройствах, исследовательские документы
Изучает лекарственный продукт, регулируемый FDA США.
Изучает продукт устройства, регулируемый Управлением по санитарному надзору за качеством пищевых продуктов и медикаментов США.
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