Evaluation of Efficacy and Safety of Autologous MSCs Combined to Biomaterials to Enhance Bone Healing
Condition: Delayed Union After Fracture of Humerus, Tibial or Femur
MeSH terms: Humeral Fractures
Study type: Interventional
Phase: Phase 1/Phase 2

Summary: 
      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.
    

Detailed description: 
      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.
    

Intervention name(s): Implantation of bone substitute plus autologous cultured mesenchymal cells
Intervention type(s): Procedure
Intervention description(s): Implantation surgery of a synthetic bone substitute associated with autologous bone marrow cells expanded
Intervention model: Single Group Assignment
Masking: None (Open Label)
Primary purpose: Treatment