Delayed Union After Fracture of Humerus, Tibial or Femur Clinical Trial
Official title:
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
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.
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.
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