Modélisation multi-échelle de l'os trabéculaire humain pour la conception d'un scaffold biomimétique optimal pour l'ingénierie des tissus osseux

Bone homeostasis is a complex process that ensures the renewal and repair of bone tissue. This tissue, both biomechanical and biological, has a dynamic three-dimensional architecture. In cases of fracture, healing is generally efficient, but it becomes compromised in "critical" defects, where spontaneous regeneration is insufficient. A promising approach to overcoming this challenge is bone tissue engineering, which involves implanting a biomaterial'called a scaffold'designed to mimic the properties of bone tissue and promote in situ bone formation (osteoconduction, osteoinduction, and osteogenicity). To be effective, the scaffold must replicate the cellular environment of bone in terms of chemical composition and mechanical stresses. It should support the adhesion, proliferation, and differentiation of osteocompetent cells while transmitting physiological mechanical stimuli. Bone tissue is a composite consisting of an inorganic phase (primarily carbonated hydroxyapatite), an organic matrix (mostly type I collagen), and water. This structure provides rigidity, elasticity, toughness, and resistance to multidirectional loads. The extracellular matrix (ECM) plays a central role in cellular metabolism. Thus, biomimetic scaffolds must accurately replicate its mechanical and biochemical properties. While biological functionality depends on chemical composition, mechanical performance is influenced by material geometry. The mechanosensitivity of bone cells means that local architectural variations can alter their behavior. Assessing the biomechanical performance of scaffolds must be done at different scales. At the macroscopic level, key criteria include structural integrity and permeability. At the microscopic level, stress and strain distribution must be analyzed, as they determine cellular response. This thesis aims to identify the mechanical stresses perceived by cells within trabecular bone, the ideal physiological microenvironment. Its porous, interconnected structure provides optimal mechanical and biological conditions for these cells. Banked trabecular bone, used as a clinical reference, is currently the closest model available. This research proposes a multi-scale approach to understand the influence of: i) in vivo mechanical loading, ii) trabecular microarchitecture, iii) ECM viscoelasticity on the cellular microenvironment. It is structured around four major axes: 1) Micromechanical analysis of trabecular bone under physiological loads (compression) to study the impact of microarchitecture on local deformations. 2) Cellular perception of fluid flow, linked to permeability and local curvature, to assess wall shear stresses. 3) Viscoelastic characterization of demineralized trabecular bone to understand the combined effect of structure and chemical composition on scaffold mechanical response. 4) In vitro validation via 3D cell culture to test the regenerative potential of decalcified bone. The results highlight the importance of local curvature and viscoelastic behavior in designing advanced biomimetic scaffolds. At the microscopic scale, the study identifies key parameters influencing cellular stress perception: trabecular microarchitecture, surface curvature, and viscoelasticity. These elements must be integrated into the development of future scaffolds optimized for bone regeneration.