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Multiscale analysis of multi-layered tissues constructs : interfaces in the musculo-skeletal system based on tissue engineered osteotendinous junctions

Abstract : The objective of this thesis was the development of a biohybrid substitute for the reconstruction of the bone-tendon continuum based on tissue engineering strategies. After an exhaustive bibliographic analysis of the native structures and their environment, we first proposed the realization of each system separately using electrospun polycaprolactone scaffolds. At first, we combined electrospinning with electrospraying techniques to produce a PCL-hydroapatite scaffold with honeycomb cavities. Our hypothesis was to provide the substitute with a biomimetic structure favoring cell adhesion, spreading and differentiation. The in vitro mechanical and biological analysis performed with a progenitor cell line and withorganotypic assays confirmed our original approach. Then, the material seeded with bone marrow stem cells was successfully implanted by our collaborators in Amiens with the objective of treating a maxillofacial defect in a rodent model. In parallel, for the tendon reconstruction, we investigated several electrospinning processes, varying fibers’ size and organization (random/aligned). In a bioinspired perspective, we combined the choice of the scaffold with dynamic stretching to reproduce physical training. Under those mechanical stimulations, established first with the same progenitor cell line, we demonstrated in a second study that MSCs aligned with the stretching axis and produced extracellular matrix, which in turn allowed to keep the mechanical properties of the biohybrid scaffold all over the 2 weeks of culture. We demonstrated that cell differentiation towards tendon and bone lineage was successfully achieved in the absence of any differentiation factor, being specifically related to materials properties and mechanotransduction. Therefore, the next step consisting in the assembly of both scaffolds with a transition area should lead to this bone-tendon continuum’s reconstruction.
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Alejandro García García. Multiscale analysis of multi-layered tissues constructs : interfaces in the musculo-skeletal system based on tissue engineered osteotendinous junctions. Bioengineering. Université de Technologie de Compiègne, 2019. English. ⟨NNT : 2019COMP2488⟩. ⟨tel-02533666⟩

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