Evaluation of Efficacy and Safety of Autologous MSCs Combined to Biomaterials to Enhance Bone Healing in Patients With Delayed Consolidation After Long Bone Fracture Requiring Graft Apposition or Alternative Orthobiologics
试验速览
- 阶段
- 2 期
- 状态
- 已完成
- 发起方
- 入组人数
- 30
- 试验地点
- 5
- 主要终点
- Complication rate as percentage of patients with local complications regarding the non-union treatment in the follow-up
研究概览
简要总结
Bone grafting is widely used in hospitals to repair injured, aged or diseased skeletal tissue. In Europe, about one million patients encounter a surgical bone reconstruction annually and the numbers are increasing due to our ageing population. Bone grafting intends to facilitate bone healing through osteogenesis (i.e. bone generation) at the site of damage, but this is only attained presently by including cells capable of forming bone into the augmentation.
Bone autograft is the safest and most effective grafting procedure, since it contains patient's own bone growing cells (to enhance osteogenesis) and proteins (to enhance osteoinduction), and it providing a scaffold for the new bone to grow into (osteoconduction). However, bone autograft is limited in quantity (about 20 cc) and its harvesting (e.g. from the iliac crest) represents an additional surgical intervention, with frequent consequent pain and complications.
We hypothesize that using autologous bone marrow cells expanded in GMP facility surgically implanted with synthetic bone substitutes contribute to the resolution of the health and socioeconomic complications of delayed union or non-union after diaphyseal and metaphyseal-diaphyseal fractures with safety and efficacy.
详细描述
Tissue engineering combines bone marrow cells or mesenchymal stem cells (MSCs), synthetic scaffolds and molecular signals (growth or differentiating factors) in order to form hybrids constructs. For bone reconstruction purposes, human MSCs have been seeded and cultured on porous calcium phosphate ceramics in osteogenic media. Some clinical studies with low numbers of patients have been reported using this approach but the outcomes were inconsistent with low efficacy in bone regeneration. The reasons of the limited clinical success may be due to several bottlenecks in the multidisciplinary field of bone tissue engineering. The association in vitro of biomaterials and osteoprogenitor cells raises technical challenges and regulatory and ethic issues for the implementation of clinical trials, whereas the expansion of MSCs is now possible in GMP Facility.
The expected results are to obtain bone consolidation thus healing of delayed union or non-union, as proven by imaging techniques, without using bone graft. This will prove the efficacy of the proposed IMP based on pluripotent MSCs expanded in a GMP facility and mixed with granulated biphasic calcium phosphate in the surgical setting before implantation. No expected complications related to the procedure are expected. Changes in serum levels of bone turnover markers will be described.
研究设计
- 研究类型
- Interventional
- 分配方式
- Na
- 干预模型
- Single Group
- 主要目的
- Treatment
- 盲法
- None
入排标准
- 年龄范围
- 18 Years 至 65 Years（Adult, Older Adult）
- 性别
- All
- 接受健康志愿者
- 否
入选标准
- •Age 18 to 65, both sexes
- •Traumatic isolated closed or open Gustilo I and II humerus, tibial or femur diaphyseal or metaphyseal-diaphyseal fracture status delayed union or non-union
- •At least 3 months from acute fracture
- •Able to provide informed consent, and signed informed consent
- •Patients (by themselves) should have medical health care coverage to be included in a research study
- •Able to understand and accept the study constraints
排除标准
- •Pregnancy, breast feeding women and women who are of childbearing age and not practicing adequate birth control
- •Participation in another therapeutic trial in the previous 3 months
- •Delayed union or non-union related to iatrogeny
- •Segmental bone loss requiring specific therapy (bone transport, large structural allograft, megaprosthesis, etc)
- •Vascular or neural injury
- •Other fractures causing interference with weight bearing
- •Acute persistent chronic bacterial infections such as brucellosis, typhus, leprosy, relapsing fever, melioidosis and tularemia
- •Visceral injuries of diseases interfering with callus formation (cranioencephalic trauma, etc.)
- •History of bone harvesting on iliac crest contraindicating bone-marrow aspiration
- •Corticoid or immunosuppressive therapy more than one week in the three months prior to study inclusion
- •History of prior or concurrent diagnosis of HIV-, Syphilis, Hepatitis-B- or Hepatitis-C-infection (confirmed by serology or PCR)
- •History of neoplasia or current neoplasia in any organ
- •Subject legally protected, under legal guardianship, deprived of their liberty by judicial or administrative decision, subject of psychiatric care, or admission to a health facility.
- •Impossibility to meet at the appointments for the follow up
- •Insulin dependent diabetes
- •Obesity (BMI > 30)
- •Autoimmune inflammatory disease
- •Current treatment by biphosphonate or stopped in the three months prior to study inclusion.
研究组 & 干预措施
Implantation surgery
All the patients will have the implantation surgery. This trial is a one-arm study.
干预措施: Implantation of bone substitute plus autologous cultured mesenchymal cells (Biological)
结局指标
主要结局
Complication rate as percentage of patients with local complications regarding the non-union treatment in the follow-up
时间窗: At 6 weeks, 12 weeks, 24 weeks and 52 weeks after the implantation surgery
次要结局
- Changes in serum levels of bone turnover markers(6 weeks, 12 weeks, and 24 weeks after the implantation surgery)
- Number of patients with proven bone healing(6 weeks, 12 weeks, and 24 weeks after the implantation surgery)
- Amount of radiological callus(6 weeks, 12 weeks, and 24 weeks after the implantation surgery)
- Clinical consolidation(6 weeks, 12 weeks, and 24 weeks after implantation surgery)
- No reoperation done or scheduled(24 weeks after implantation surgery)