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Bone regeneration into 3D architectured and osteoinductive titanium scaffolds

Abstract : To date, titanium-based alloys (Ti) remain the most used implantable materials for load-bearing applications. Emerging additive manufacturing techniques such as electron beam melting (EBM) enable to custom-build architectured scaffolds of controlled macroporosity. In very difficult clinical situations, potent bioactive signals are needed to boost stem cells: osteoinductive molecules such as bone morphogenetic proteins (BMP-2) are currently used for this purpose. However, one of their limitations is their inappropriate delivery with collagen sponges. Biomimetic surface coatings made of the biopolymers poly(L-lysine) and hyaluronic acid, (PLL/HA) polyelectrolyte films, have recently been engineered as nanoreservoirs for BMP proteins. The aim of this PhD thesis was to develop architectured and osteoinductive 3D titanium-based scaffolds as innovative synthetic bone grafts. To this end, we used the EBM additive manufacturing technique to engineer porous scaffolds with cubit unit-cells. Their surface was coated with biomimetic films containing the bone morphogenetic protein 7 (BMP-7). The porosity was well controlled with a difference from CAD models of less than 1%. The osteoinductive capacity of BMP-7 loaded films was assessed using murine mesenchymal stem cells (MSCs) by quantifying their alkaline phosphatase (ALP) expression, which increased in a dose-dependent manner. The coating of the 3D architectured scaffolds by the bioactive film was characterized using optical and electron microscopy techniques. Finally, the 3D architectured scaffolds coated with BMP-7-loaded films were proved to be osteoinductive at the early stage in vitro. Preliminary experiments are currently done to assess their performance in an in vivo model of a critical size femoral bone defect in rat.
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Antalya Ho-Shui-Ling. Bone regeneration into 3D architectured and osteoinductive titanium scaffolds. Medical Physics [physics.med-ph]. Université Grenoble Alpes, 2018. English. ⟨NNT : 2018GREAI087⟩. ⟨tel-02887097⟩

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